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Hydrogen sulfide: A new gaseous signal molecule and blood pressure regulator
Abstract
The gas hydrogen sulfide (H2S) is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow and leukocyte adhesion. In addition, it may have antiinflammatory and antiapoptotic effects. H2S has recently attracted much interest as a potent vasorelaxative substance that may establish itself alongside another gaseous signal molecule, nitric oxide (NO). In contrast to NO, the major source of H2S in blood may be production by red blood cells or by vascular smooth muscle cells. H2S is produced from cysteine, involving the enzymes cystathionine beta-synthase and cystathionine gamma-lyase (CSE). The importance of CSE was recently demonstrated in a mouse lacking CSE which showed reduced H2S levels and developed hypertension and reduced endothelium-mediated vasorelaxation. These data establish H2S as a new and important biologic signal molecule and as a new regulator of vascular blood flow and blood pressure.
... The evidence of defective and enhanced H 2 S production under HHCy conditions and the metabolic imbalance of HCy and H 2 S in cardiovascular pathologies suggests that changes in the H 2 S/HCy ratio may be more valuable than changes in the absolute concentrations of H 2 S and HCy in depicting the role of these metabolites in disease pathogenesis [88][89][90]. There are growing controversies on the physiologically significant concentrations of H 2 S and its biological effects [91,92]. H 2 S stimulates or inhibits intracellular transduction pathways, cell proliferation, apoptosis and hemostasis [59,[93][94][95][96][97][98]. ...
... Only a few studies showed changes in the levels of H 2 S in human diseases, and most of these measurements were indirect and measured compounds linked to H 2 S, such as thiosulfate or sulfhemoglobin, rather than H 2 S itself [101]. Due to its vasorelaxative and vasoprotective properties, H 2 S may be useful in the treatment of arterial hypertension by decreasing peripheral resistance [92]. Research on the clinical and fundamental aspects of H 2 S is in full development, particularly the relationship between the production of H 2 S and epigenetics such as DNA methylation and DNA damage repair [102]. ...
The influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H2S) is a cardioprotector. Previous research proposed a positive role of H2S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H2S, which decreases the expression of adenosine A2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively.
... The pathogenesis of GDM remains unclear, but the discovery of gas-signaling molecules provides a new facet for GDM research. Hydrogen sulfide (H 2 S) is the third endogenous gas-signaling molecule discovered in recent years and is produced mainly by cysteine under the action of CSE (cystathionine-γ-lyase) in cardiovascular tissue [2,3]. Previous research has found that H 2 S levels were downregulated in gestational hypertension (GH) patients [4,5]. ...
... As an endogenous gas-signaling molecule, H 2 S has many biologically important characteristics, such as small molecular weight, continuous production, rapid diffusion, and wide effects. It is generated in cardiovascular tissues under the action of CSE with cysteine as the main substrate [2,3]. Some studies have found that the disorder of the H 2 S/CSE system is important in the pathogenesis of many vascular injury diseases [11,12]. ...
Background:
Gestational diabetes mellitus (GDM) is a severe threat to the health of both mother and child. The pathogenesis of GDM remains unclear, although much research has found that the levels of hydrogen sulfide (H2S) play an important role in complications of pregnancy.
Methods:
We collected venous blood samples from parturient women and umbilical vein blood (UVB) and peripheral venous blood (PVB) samples one hour after childbirth in the control, GDM-, and GDM+ groups in order to determine the concentration of glucose and H2S in plasma; to measure levels of TNF-α, IL-1β, IL-6, TGF-β1, and ADP in parturient women and the UVB of newborns; and to find the correlation of H2S with regression.
Results:
We found that, with the elevation of glucose, the level of H2S was decreased in GDM pregnant women and newborns and the concentrations of IL-6 and TNF-α were upregulated. With regression, IL-6 and TNF-α concentrations were positively correlated with the level of blood glucose and negatively correlated with H2S concentration.
Conclusion:
This study shows that downregulation of H2S participates in the pathogenesis of GDM and is of great significance in understanding the difference of H2S between normal and GDM pregnant women and newborns. This study suggests that IL-6 and TNF-α are correlated with gestational diabetes mellitus. The current study expands the knowledge base regarding H2S and provides new avenues for exploring further the pathogenesis of GDM.
... Plutôt que d'augmenter l'apport en oxygène pour répondre à cette demande accrue, un état d'hypométabolisme permettrait par la diminution de la consommation d'oxygène de limiter la défaillance d'organes au cours de pathologies aiguës, comme le sepsis. L'hypothermie induite permet en diminuant le métabolisme d'améliorer le pronostic neurologique ou de préserver les tissus des lésions hypoxiques(Polderman 2008).L'H 2 S peut induire un état réversible d'hypothermie et d'hypométabolisme(Safar and Tisherman 2002;Nozari, Safar et al. 2004) notamment chez les rongeursBlackstone and Roth 2007), ressemblant à un état d'hibernation(Wagner 2009). L'effet de l'H 2 S comme inducteur d'hibernation a initialement été mis en évidence chez les éspèces inférieures, notamment chez les nématodes(Padilla and Roth 2001;Padilla, Nystul et al. 2002;Nystul and Roth 2004), associant la diminution de la consommation et de la production d'énergie. ...
... Ce mécanisme est nécessaire au maintien de l'homéothermie chez le petit mamifère, mais est absent chez les plus gros animaux ou chez l'homme adulte. L'H 2 Spourrait avoir un effet métabolique direct chez le gros mammifère(Wagner 2009;Derwall, Francis et al. 2011;Wagner, Georgieff et al. 2011).Avec le NO et CO, H 2 S est le troisième médiateur gazeux de l'organisme(Lowicka and Beltowski 2007). Comme les autres gasotransmetteurs, H 2 S traverse librement les membranes cellulaires, sans transporteur spécifique. ...
L'ischémie/reperfusion (I/R) est un phénomène très fréquent en clinique humaine. Ce phénomène est observé lors de la désobstruction d'une artère digestive, du traitement d'un état de choc, ainsi qu'au cours d'autres pathologies. L'interruption de la perfusion tissulaire (ischémie) et le rétablissement de celle-ci (reperfusion) sont la cause de la mise en place de troubles hémodynamiques et métaboliques. L'I/R est souvent présentée comme étant la principale source de l'hyperlactatémie et le moteur de la réponse inflammatoire lors des états de choc (cardiogénique, hypovolémique, septique). Parallèlement, elle est responsable de l'induction de la production de la libération des espèces réactives de l'oxygène, des cytokines et du monoxyde d'azote. Suite à un choc hémorragique par Ischémie/reperfusion chez le rat, nous avons montré que 1) le NaHS, donneur d'H2S limite la diminution de la pression artérielle moyenne et diminue le lactate plasmatique, témoin de la souffrance tissulaire, 2) cette amélioration hémodynamique est associée à une baisse de l'expression myocardique des ARNm d'iNOS, une diminution de la concentration des dérivés NOx plasmatiques et une diminution des concentrations aortiques et myocardiques de NO et d'anion superoxyde et 3) l'inhibition d'H2S par la DL-propargylglycine aggrave le tableau hémodynamique et les conséquences tissulaires du choc. Dans un autre modèle d'ischémie/reperfusion intestinale, les résultats obtenus, montrent que l'administration de la Protéine C activée (PCa) ou de la dexaméthaosne (Dexa) : 1) améliore la PAM et la réactivité vasculaire, 2) permet d'augmenter le pH et de diminuer la lactatémie, 3) diminue la production des cytokines pro-inflammatoires et 4) inhibe les médiateurs de l'apoptose. Ces résultats sont reliés à une down régulation d'iNOS, une restauration de la voie Akt/eNOS et à une resensibilisation des adrénorécepteurs alpha. Ces résultats ouvrent de nouvelles perspectives cliniques dans les traitements de l'I/R
... Согласно многочисленным данным, сероводород (H 2 S) является важным регулятором тонуса кровеносных сосудов [115,135,166,203,268,270,272,275,276,304,305]. Он вызывает расслабление сосудистых ГМК, причем степень H 2 S-индуцированного расслабления превосходит таковую при действии NO [276,288,303,304]. ...
... 98. Aguilar-Bryan L., Nichols C. G., Wechsler S. W. et al.Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion // Science. 1995.268. P. 423-426. ...
Gaseous signaling molecules (gas transmitters) take an especial position among the numerous signaling molecules involved in the regulation of both intracellular processes that occur in different types of cells and cell-cell interactions. At present time, gas transmitters include three molecules whose enzymatic systems of synthesis and degradation, physiological action and intracellular effectors, the change of which under the action of gas transmitters may result in physiological and/or pathophysiological effects are well- determined. These molecules include nitrogen oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). They are involved in the regulation of functions of various organs and systems of the human body, including the circulatory system. Interaction of NO, CO and H2S with various enzymatic and structural components of endothelial and, especially, smooth muscle cells has a significant impact on vascular tone and blood pressure. Furthermore, the crossing of NO-, CO- and H2S-mediated signaling pathways at common effectors and interaction with each other can determine the end, resulting functional response of the cell. The knowledge of the molecular targets of gas transmitters' action, the structure of the binding centers for gas transmitters and their interaction with each other may be essential in the development of methods of regulation of these signaling systems by targeted, directed action. This review summarizes the molecular mechanisms of the NO, CO and H2S interaction with the main targets, which carry out their regulatory effect on vascular smooth muscle cells. Also we describe here different ways of cross-regulation of NO-, CO- and H2S-dependent signaling pathways. We analyzed NO-synthase and nitrite reductase systems of nitric oxide cycle and discuss the nitrate-nitrite background of the existence of modern man, which can substantially modify the signaling system, the metabolism of virtually all cell ultrastructure of neurons, neuron-neuron and neuron-glial interactions and exerts its influence on socially significant diseases that can affect the quality and the average life expectancy.
... Hydrogen sulfide (H 2 S), for centuries considered as a toxic gas with its characteristic odor of rotten egg, displays both acute and chronic toxicity at high concentrations [1][2][3]. On the other hand, recently, H 2 S has emerged as the third endogenous gaseous signaling compound (gasotransmitter) along with nitric oxide (NO) and carbon monoxide (CO) [4,5]. More recent studies have demonstrated that H 2 S is also produced via enzymatic reaction in the brain and several smooth muscles and can mediate a wide range of physiological processes, such as vasodilation, antioxidation, anti-apoptosis, and anti-inflammation [5][6][7][8]. ...
... On the other hand, recently, H 2 S has emerged as the third endogenous gaseous signaling compound (gasotransmitter) along with nitric oxide (NO) and carbon monoxide (CO) [4,5]. More recent studies have demonstrated that H 2 S is also produced via enzymatic reaction in the brain and several smooth muscles and can mediate a wide range of physiological processes, such as vasodilation, antioxidation, anti-apoptosis, and anti-inflammation [5][6][7][8]. The abnormal level of H 2 S was closely associated with diseases such as Alzheimer's disease, hypertension, liver cirrhosis, and Down's syndrome [9][10][11]. ...
Hydrogen sulfide (H2S) has attracted attention in biochemical research because it plays an important role in biosystems and has emerged as the third endogenous gaseous signaling compound along with nitric oxide (NO) and carbon monoxide (CO). Since H2S is a kind of gaseous molecule, conventional approaches for H2S detection are mostly based on the detection of sulfide (S²⁻) for indirectly reflecting H2S levels. Hence, there is a need for an accurate and reliable assay capable of determining sulfide in physiological systems. We report here a colorimetric, economic, and green method for sulfide anion detection using in situ formation of silver nanoparticles (AgNPs) using dopamine as a reducing and protecting agent. The changes in the AgNPs absorption response depend linearly on the concentration of Na2S in the range from 2 to 15 μM, with a detection limit of 0.03 μM. Meanwhile, the morphological changes in AgNPs in the presence of S²⁻ and thiol compounds were characterized by transmission electron microscopy (TEM). The as-synthetized AgNPs demonstrate high selectivity, free from interference, especially by other thiol compounds such as cysteine and glutathione. Furthermore, the colorimetric sensor developed was applied to the analysis of sulfide in fetal bovine serum and spiked serum samples with good recovery.
... It has been suggested that H 2 S is a signalling molecule in animals [3][4][5][36][37][38] and that it is likely, therefore, that the same is true for plants [34,35]. However, to be a signal, H 2 S needs to be perceived by plant cells and there needs to be a response. ...
... However, at the same time that glutathione was being altered photosynthetic carbon fixation and photosynthetic electron transport were reported to be insensitive to the presence of H 2 S [37]. Fumigation of poplar (Populus tremulaÂPopulus alba) cuttings with H 2 S showed that a significant amount of the H 2 S was incorporated into organic sulphur compounds. ...
... Schwefelwasserstoff kann über vier Bildungswege synthetisiert werden, wobei man enzymatische von Enzym-unabhängigen Bildungswegen unterscheiden kann (siehe Abbildung 6). 79,138,156 H 2 S wird endogen von zwei Pyridoxal-5`-Phosphat (Vitamin B6) abhängigen Enzymen synthetisiert, der ...
... Sulfur zu H 2 S dar, wofür reduzierende Äquivalente aus der Oxidation von Glukose benötigt werden. 159 Er läuft hauptsächlich in Erythrozyten ab und benötigt Glutathion (GSH), es entstehen oxodiertes Glutathion (GSSG) und H 2 S. 156 ...
Hintergrund: Eine der gefürchtetsten Komplikationen in den ersten Tagen nach einer Pankreastransplantation stellt das Auftreten einer frühen postischämischen Transplantatpankreatitis dar, die bei schwerem Verlauf sogar bis zu einem Transplantatverlust führen kann. Veränderungen insbesondere der Mikrozirkulation stellen dabei wesentliche Ereignisse bei der Initiation und Progression der Transplantatpankreatitis dar. Das Erforschen der genauen Mechanismen dieser vaskulären Dysfunktion und ihrer molekularen Steuerungsmechanismen am Pankreas ist unabdingbare Voraussetzung dafür, dass wirksame therapeutische Ansätze auf diesem Gebiet etabliert werden können. Viele tierexperimentelle Studien in den letzten Jahren konnten zeigen, dass der Gasotransmitter Schwefelwasserstoff (H2S) neben der physiologischen Regulation verschiedener Signalwege auch bei einer Reihe von pathophysiologischen Prozessen wie Ischämie/Reperfusion, Inflammation und oxidativem Stress eine entscheidende Rolle zu spielen scheint. Ziel dieser Studie war es zu untersuchen, ob der Gasotransmitter H2S zytoprotektive und anti-iflammatorische Eigenschaften im Zuge der Ischämie/Reperfusionsschädigungen im Rahmen einer Pankreastransplantation ausüben kann.
Methode: Hierzu wurden männliche Sprangue-Dawley Ratten randomisiert in drei Gruppen eingeteilt und nach folgendem Protokoll analysiert: 1.Gruppe: unbehandelte Kontrollgruppe, 2.Gruppe: einstündige Ischämie/Reperfusion, 3.Gruppe: NaHS-Gabe + einstündige I/R. Das verwendete Modell zur Induktion der postischämischen Pankreatitis in Gruppe 2+3 war das Modell der normothermen I/R nach Hoffmann. Die mikrovaskuläre Dysfunktion wurde intravitalmikroskopisch mittels analoger bzw. digitaler Video-Epifluoreszenzmikroskopie mit den Parametern Mikrovaskuläre Permeabilität (P), Funktionelle Kapillardichte (FKD) und Leukozyten-Endothelzell-Interaktion (LEI) ausgewertet. Zusätzlich wurde eine Korrelation der mikrovaskulären Dysfunktion mit den histologischen Schädigungen (HE-Schnitte), dem Prozentualen Trockengewicht sowie den exokrinen Pankreasmarkern (Amylase, Lipase) untersucht.
Ergebnisse: Nach einstündiger I/R konnten die typischen Charakteristika einer postischämischen Pankreatitis festgestellt werden: Es resultierte eine signifikante Verschlechterung aller erhobenen mikrozirkulatorischen Parameter, ein signifikanter Abfall des Prozentualen Trockengewichts im Sinne einer erhöhten Ödembildung, histomorphologisch das Bild einer akut-ödematösen Pankreatitis sowie ein signifikanter Anstieg beider exokriner Pankreasmarker. Eine Behandlung mit dem H2S-Donor Natriumhydrogensulfid (NaHS) konnte der mikrovaskulären Dysfunktion (P↑, FKD↓, LEI↑), dem Abfall des Prozentualen Trockengewichts und den histomorphologischen Schädigungen eindeutig entgegenwirken. Entgegen unseren Erwartungen konnte aber keine Verbesserung der exokrinen Parameter (Amylase, Lipase) erzielt werden.
Schlussfolgerung: Aufgrund der erhobenen Ergebnisse dieser tierexperimentellen Studie konnte gezeigt werden, dass der Gasotransmitter H2S zytoprotektive und antiinflammatorische Auswirkungen bei der postischämischen Pankreatitis ausübt und Gegenstand weiterer Forschung bleiben sollte, um auch in Zukunft im Setting von Organtransplantationen gezielt eingesetzt werden zu können um die Schädigungen durch I/R zu vermindern.
... In recent years, hydrogen sulfide (H 2 S) has gained attention as a gaseous signaling molecule in the response of plants to biotic and abiotic stresses, like nitric oxide and carbon monoxide (da-Silva and Modolo 2017). H 2 S was reported to be involved in physiological processes such as blood pressure regulation, anti-inflammatory effects, and vasorelaxation in mammalian studies (Wagner 2009). As the effects of H 2 S, activation of photosynthesis (Ali et al. 2014, Chen et al. 2011, Duan et al. 2015, stomatal opening and closure (Papanatsiou et al. 2015, Jin et al. 2017, Shen et al. 2020, seed germination (Zhang et al. 2008), root formation (Zhang et al. 2009, Jia et al. 2015, Mei et al. 2019, and fruit maturation (Ge et al. 2017, Munoz-Vargas et al. 2018) have already been reported. ...
Hydrogen sulfide (H 2 S) has been recently found to be a signaling molecule to environmental stress tolerance. This study was conducted to investigate the effects of irrigation (Experiments 1 and 2) and foliar application (Experiment 3) of sodium hydrosulfide (NaHS), as a H 2 S donor, under NaCl stress. A Bangladeshi salt-tolerant soybean genotype 'AGS313' was compared with a salt-sensitive Japanese variety 'Fukuyutaka'. While the shoot dry weight was improved by NaHS application in the experiment 1, the vegetative growth was not improved by NaHS application in the experiments 2 and 3. NaHS irrigation decreased leaf Cl content, while NaHS foliar application increased photosynthetic rate. These results showed that NaHS application had slightly positive effects on soybean under NaCl stress conditions.
... Due to the production of hydrogen sulfide, cystathionine γ-lyase functions as a sulfhydrase of cysteine-containing proteins, regulating their functions by sulfhydrogenation through the conversion of SH-groups to SSH-groups at specific cysteine residues [36]. Most likely, the data obtained testify to the modification of SH-groups which may be accompanied by changes in the conformational structure of protein molecules. ...
In recent years, there has been extensive evidence of the involvement of disorders in the metabolism of sulfur-containing amino
acids - methionine, cysteine and homocysteine - in the development of several diseases. These amino acids share common degradation pathways, and their intermediates play a role in regulating the activity of homocysteine remethylation and enzymes transsulfuration.
In this study, we aimed to evaluate the effect of acetaminophen on the background of dietary protein deficiency on the metabolism
of sulfur-containing amino acids in rats: distribution of sulfur-containing amino acids - homocysteine, cysteine and methionine − in
blood serum and hepatocytes, activity of key enzymes of the transsulfuration pathway of homocysteine metabolism - сystathionine
beta-synthase, сystathionine gamma-lyase.
During the experiment, the experimental animals consumed a semi-synthetic diet AIN-93 in accordance with the recommendations of the American Institute of Nutrition. In order to model the alimentary protein deprivation rats received a low-protein diet
daily for 28 days, which contained 1/3 of the generally accepted daily requirement of protein. After four weeks of keeping animals on
an experimental diet, acute toxic damage with acetaminophen was modelled. The toxin was administered at 1250 mg/kg of animal
weight as a suspension in a 2% solution of starch gel once a day for 2 days.
Our results indicate that the conditions of alimentary protein deprivation and acetaminophen toxic injury in hepatocytes and
blood serum of animals disrupts the distribution of sulfur-containing amino acids (decrease in methionine, increase in cysteine concentration) with the development of hyperhomocysteinemia: in the absence of dietary protein - a mild form, with the introduction of
toxic doses of acetaminophen - moderate.
The results confirm the causal relationship between the functioning of the transsulfuration pathway of homocysteine (decreased
cystathionine β-synthase activity with simultaneous activation of cystathionine γ-lyase in animal hepatocytes) and the maximum
increase in the level of this amino acid in blood serum under conditions of acetaminophen-toxic injury.
Elevated blood homocysteine levels can therefore be considered as a prognostic marker of functional abnormalities in the liver
transsulfuration pathway and can be used in the diagnosis of hepatic pathologies.
... urinary H 2 S concentrations as well as vascular CSE expression and activity have been reported to be reduced in SHR model and in hypertension induced by NO synthase inhibitor [43,44]. Further, d'Emmanuele et al. [45] reported significant reduction in CBS and CSE expressions in mesenteric arterial bed and carotid artery in parallel with reduced plasma H 2 S in a rat model of dexamethasoneinduced hypertension. ...
Hypertension is the most common cause of cardiovascular morbidities and mortalities, and a major risk factor for renal dysfunction. It is considered one of the causes of chronic kidney disease, which progresses into end-stage renal disease and eventually loss of renal function. Yet, the mechanism underlying the pathogenesis of hypertension and its associated kidney injury is still poorly understood. Moreover, despite existing antihypertensive therapies, achievement of blood pressure control and preservation of renal function still remain a worldwide public health challenge in a subset of hypertensive patients. Therefore, novel modes of intervention are in demand. Hydrogen sulfide (H 2 S), a gaseous signaling molecule, has been established to possess antihypertensive and renoprotective properties, which may represent an important therapeutic alternative for the treatment of hypertension and kidney injury. This review discusses recent findings about H 2 S in hypertension and kidney injury from both experimental and clinical studies. It also addresses future direction regarding therapeutic use of H 2 S.
... It has been recently demonstrated that chicken RBCs, which contain an intact nucleus and mitochondria, produce H 2 S, mainly from MST enzyme (63). Human RBCs, which lack the nucleus and mitochondria, may produce limited H 2 S by sulfur reduction nonenzymatically (12,142,170). Jennings demonstrated that deprotonated H 2 S in the form of HS -can be transported into the RBCs in exchange for a chloride ion through AE1 anion exchange protein as part of the Jacobs/Stewart cycle. The HScan be converted to H 2 S in cells, which can take part in cellular functions or diffuse out (58). ...
Significance:
Hydrogen sulfide (H2S) is an endogenous signaling molecule, regulating numerous physiological functions from vasorelaxation to neuromodulation. Iron is a well-known bioactive metal ion, being the central component of hemoglobin for oxygen transportation and participating in biomolecule degradation, redox balance, and enzymatic actions. The interplay between H2S and iron metabolisms and functions impact significantly on the fate and wellness of different types of cells. Recent advances: Iron level in vivo affects the production of H2S via non-enzymatic reactions. On the other hand, H2S quenches excessive iron inside the cells and regulates the redox status of iron.
Critical issues:
Abnormal metabolisms of both iron and H2S are associated with various conditions and diseases like iron overload, anemia, oxidative stress, cardiovascular and neurodegenerative diseases. The molecular mechanisms for the interactions of H2S and iron are unsettled yet. Here we review signaling links of the production, metabolism and their respective and integrative functions of H2S and iron in normalcy and diseases. Future direction: Physiological and pathophysiological importance of H2S and iron as well as their therapeutic applications should be evaluated jointly, not separately. Future investigation should expand from iron-rich cells and tissues to the others in which H2S and iron interaction has not received due attention.
... До них відносять оксид азоту (NO), монооксид вуглецю (СО) і сульфід водню (H 2 S) [39]. Серед досліджених газотрансмітерів H 2 S найменш вивчений [20]. Варто нагадати, що усі гази, у тому числі і газові трансмітери є низькомолекулярними речовинами, які мають досить важливі для біологічних процесів фізичні характеристики − високу швидкість дифузії, різну розчинність у воді при різних температурах і парціальному тиску (табл. ...
Medical hydrology and rehabilitation 2013.-11, №1. – P. 117-122.
The role of endogenous hydrogen sulfide in the regulation of vascular tone, cell proliferation and apoptosis was analysed. The data pertains to endogenous formation and the mechanisms of hydrogen sulfide action. Information about the cardio-, nephro-and cytoprotection of gazotransmitter was summarized. In experimental systems, H2S or H2S donors (most commonly NaHS) provide protection in many physiological systems, including the cardiovascular system, brain, lungs, and gastrointestinal system. Most notably, they attenuate vasoconstriction and reduce damage (e.g., myocardial infarct size) in several animal models of cardiovascular disease (e.g., myocardial ischemia-reperfusion, cardiopulmonary bypass). Conversely, inhibitors of H2S synthesis raise blood pressure in rats. The effects of H2S on cells, studied using H2S donors, are variable. In part, effects are dose dependent. Lower (micromolar) levels are generally cytoprotective, with protection often ascribed to a reduction or neutralization of reactive oxygen and nitrogen species. At millimolar levels, H2S is often cytotoxic or pro-apoptotic.
... ! " (H 2 S) 2500 1700 , [14,20,34,36], ...
We analysed the modern literature about the hydrogen sulfide role in evolution of atmosphere, phylogenesis and possibility the use of its vazodylyatation properties for treatment and rehabilitation in sanatorium-resort terms. The mechanisms of gumoral and reflex action of hydrogen sulfide and sulfides baths are considered, testimonies, relative and absolute contra-indications, are resulted. It was shown that at the correct dosage and account of the initial state of reactivity of patient hydrogen sulfide can be the substantial factor for the local blood stream improvement, the trophic and regeneration processes activating, the whole organism physiological state renewal.
... Бюллетень сибирской медицины, ¹ 6, 2010 13 наиболее загадочным и функционально наиболее значимым газовым посредником [8]. Сероводород, хорошо известный токсичный газ, в клетках млекопитающих эндогенно продуцируется тремя ферментами (цистотионин-β-синтазой, цистотионин-γ-лиазой и 3-меркаптопируват-сульфуртрансферазой) и играет важную роль в физиологических условиях и при патологических состояниях [1,6,7]. В центральной нервной системе сероводород функционирует как нейромодулятор, но может выполнять и протекторную функцию при оксидативном стрессе. ...
In preparations of rat aorta, used as a model of muscular type arteries, the method mehanografii studied the effect of hydrogen sulfide on the reduction of isolated of vascular smooth muscle. Found that hydrogen sulfide in concentrations 1—50 mmol increases the mechanical stress of smooth muscle in high-K + medium. At higher concentrations (300—1 000 mmol) H2S leads to lower amplitude giperkalievoy contraction in high-K + medium. Reduction of smooth muscle cells caused by phenylephrine inhibited the action of hydrogen sulfide in the whole range of concentrations. The causes of differences in data obtained with the results of studies in other laboratories, and possible mechanisms of action of hydrogen sulfide on the contractile activity of vascular smooth muscle.
... Ретроградно, но все больше уделяется внимания такому соединению, как сероводород (H 2 S) [3,4,8,10,13,16]. Если раньше он рассматривался только с позиции своего токсического воздействия [11,12,18], то сейчас активно изучается и как регулятор различных физиологических параметров [17,[19][20][21]. Например, найдена зависимость между уровнем его содержания в плазме крови и развитием различных заболеваний, таких как болезнь Дауна, септический шок, спонтанная гипертензия, болезнь Альцгеймера [14,17], что позволяет считать этот газ важным звеном их патогенеза. ...
... As the third gasotransmitter along with nitric oxide and carbon monoxide, H 2 S is generated by cystathionine gamma-lyase (CSE), cystathionine betasynthase (CBS), and/or 3-mercaptopyruvate sulfurtransferase (3MST) with L-cysteine as a substrate (Suzuki et al., 2011;Wang, 2012;Yang et al., 2008). The expressions of these 3 H 2 S-generating enzymes are tissue-specific, with CSE mostly in liver, kidney, pancreas and vasculature, CBS in brain and peripheral nervous system, and 3MST in central and peripheral nervous systems (Tomita et al., 2016;Wagner, 2009). By adding a persulfide or hydropersulfide (eSSH) group to active cysteine residues in targeted proteins, termed as S-sulfhydation, H 2 S mediates various biochemical and pathophysiological processes including redox status, inflammation, energy production, and cell survival, etc (Iciek et al., 2015;Mustafa et al., 2009;Sen et al., 2012a, b;Yang et al., 2013). ...
... In addition, one of the other known H 2 S-producing enzymes, 3MST, has been found in erythrocytes. Local H 2 S production in the bloodstream may be important for vasodilatation 44,45 . A second H 2 S-producing enzyme in red blood cells underpins the importance of this metabolite in these cells or in the function of erythrocytes in the delivery of H 2 S cargo. ...
Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to H2O2, formaldehyde, and H2S, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor. The malodor was attributable to high levels of methanethiol and dimethylsulfide, the main odorous compounds in their breath. Elevated urinary excretion of dimethylsulfoxide was associated with MTO deficiency. Patient fibroblasts had low SELENBP1 protein levels and were deficient in MTO enzymatic activity; these effects were reversed by lentivirus-mediated expression of wild-type SELENBP1. Selenbp1-knockout mice showed biochemical characteristics similar to those in humans. Our data reveal a potentially frequent inborn error of metabolism that results from MTO deficiency and leads to a malodor syndrome.
... 48 The fact that endogenous H 2 S related enzyme cystathionine γlyase (CSE) is at high level may make a higher concentration of H 2 S in kidney. 49 Hence, TPSNP-1 offered exciting opportunities to quantitative analysis in various organs and was promising for clinical samples to diagnose disease. ...
Fluorescence quantitative analysis for vital biomolecules are in great demand in biomedical science owing to their unique detection advantages with rapid, sensitive, non-damaging and specific identification. However, available fluorescence strategy for quantitative detection are usually hard to design and achieve. Inspired by supramolecular chemistry, a two-photon-excited fluorescent supramolecular nanoplatform (TPSNP) was designed for quantitative analysis with three parts: host molecules (β-CD polymers), guest fluorophore of sensing probes (Np-Ad) and guest internal reference (NpRh-Ad). In this strategy, TPSNP would possess the merits of (i) improved water-solubility and biocompatibility; (ii) increased tissue penetration depth for bioimaging by two-photon excitation; (iii) quantitative and tunable assembly of functional guest molecules to obtain optimized detection conditions; (iv) a common approach to avoid limitation of complicated design by adjustment sensing probes; (v) accurate quantitative analysis by virtue of reference molecules. As a proof-of-principle, we utilized two-photon fluorescent probe NHS-Ad-based TPSNP-1 to realize accurate quantitative analysis of hydrogen sulfide (H2S), with high sensitivity and good selectivity in live cells, deep tissues and ex vivo-dissected organs, suggesting TPSNP as an ideal quantitative indicator for clinical samples. What’s more, TPSNP will pave the way for designing and preparing advanced supramolecular sensors for biosensing and biomedicine.
... Cystathionine β-synthase and cystathionine γ-lyase, involved in converting methionine to cysteine, catalyze side reactions that release H 2 S (Shatalin et al., 2011). The self-produced sulfide is known to function as a signaling molecule in mammals (Wagner, 2009) and to act as a general defense against oxidative stress to confer bacteria with resistance to antibiotics (Shatalin et al., 2011;Oguri et al., 2012). However, the prevalence of sulfide production by heterotrophic bacteria during aerobic growth has not been documented. ...
Sulfide (H2S, HS− and S2−) oxidation to sulfite and thiosulfate by heterotrophic bacteria, using sulfide:quinone oxidoreductase (SQR) and persulfide dioxygenase (PDO), has recently been reported as a possible detoxification mechanism for sulfide at high levels. Bioinformatic analysis revealed that the sqr and pdo genes were common in sequenced bacterial genomes, implying the sulfide oxidation may have other physiological functions. SQRs have previously been classified into six types. Here we grouped PDOs into three types and showed that some heterotrophic bacteria produced and released H2S from organic sulfur into the headspace during aerobic growth, and others, for example, Pseudomonas aeruginosa PAO1, with sqr and pdo did not release H2S. When the sqr and pdo genes were deleted, the mutants also released H2S. Both sulfide-oxidizing and non-oxidizing heterotrophic bacteria were readily isolated from various environmental samples. The sqr and pdo genes were also common in the published marine metagenomic and metatranscriptomic data, indicating that the genes are present and expressed. Thus, heterotrophic bacteria actively produce and consume sulfide when growing on organic compounds under aerobic conditions. Given their abundance on Earth, their contribution to the sulfur cycle should not be overlooked.
... Hydrogen sulfide (H 2 S) belongs to the class of gasotransmitters, together with nitric oxide (NO) and carbon monoxide. These endogenously produced signaling molecules are of critical importance to a functioning organism and its response to pathogens, stress, and injury [1,2]. Whereas effects of NO have been explored for some time and associations with psychological and central nervous system processes have been detailed [3], research on H 2 S is still in its infancy. ...
Background:
Hydrogen sulfide (H2S) is the third gasotransmitter recently discovered after nitric oxide (NO) and carbon monoxide. Both NO and H2S are involved in multiple physiological functions. Whereas NO has been shown to vary with psychological stress, the influence of stress on H2S and the relationship between H2S and NO are unknown. We therefore examined levels of salivary H2S and NO in response to a stressful final academic exam period.
Methods:
Measurements of stress, negative affect, and fraction of exhaled NO (FENO), were obtained from students (N=16) and saliva was collected at three time points: low-stress period in the semester, early exam period, and late exam period. Saliva was immediately analyzed for H2S with the fluorescent probe Sulfidefluor-4.
Results:
H2S increased significantly during the early exam period and FENO decreased gradually towards the late exam period. H2S, FENO, negative affect, and stress ratings were positively associated with each other: as stress level and negative affect increased, values of H2S increased; in addition, as FENO levels decreased, H2S also decreased. Asthma status did not modify these associations.
Conclusion:
Sustained academic stress increases H2S and these changes are correlated with NO and the experience of stress and negative affect. These findings motivate further research with larger samples to further explore the interaction and function of H2S and FENO during psychological stress.
... Hydrogen sulfide (H 2 S) is a toxic gas with a smell of rotten eggs 1 . It has been considered as the third biosynthetic gas transmitter following nitric oxide (NO) and carbon monoxide (CO) 2 , which was produced under the function of cystathionine-β-synthase (CBS), 5 cystathionine-γ-lyase (CSE) and 3-mercaptoacetylthio transferase (3MST) [3][4][5] . Endogenous H 2 S plays an important role in many physiological and pathological processes such as relaxation of vascular smooth muscle 6 , modulation of neurotransmission 7 , inhibition of insulin signaling 8 , regulation of inflammation 9 and 10 oxygen perception 8 . ...
A simple fluorescent probe (E)-1,3,3-trimethyl-2-(4-morpholinostyryl)-3H-indol-1-ium iodide (Mi) based on intramolecular charge transfer (ICT) was synthesized. The probe can sense hydrogen sulphide (H2S) rapidly and sensitively with low detection limit (15 nM). The reaction mechanism was investigated by fluorescence and mass spectra. Moreover, probe Mi was successfully used for fluorescent imaging of H2S in living cells, demonstrating its potential applications in biological science. Finally, agar gels based on Mi were fabricated, which could be acted as a solid optical sensor to detect H2S conveniently and efficiently.
... Sulfide (H 2 S, HS 2 and S 22 ) is produced during the synthesis and breakdown of sulfur-containing amino acids in plants, animals and microorganisms (Singh and Banerjee, 2011). It is a signalling molecule (Wagner, 2009), targeting redox sensors and heme groups in human and animal models (Olson, 2011), and regulating photosynthesis in cyanobacteria (Klatt et al., 2015). It also functions as a universal defense against antibiotics through its spontaneous reaction with reactive oxygen species (Shatalin et al., 2011). ...
... H 2 S is a gaseous molecule; together with NO and CO, it is an important gasotransmitter participating in the regulation of several intracellular processes. S-Sulfhydration, caused by H 2 S, is a possible mechanism by which H 2 S alters the function of different proteins [140][141][142][143]. To create an indicator for H 2 S, the chromophore of cpGFP was modified with sulfide-reactive azide functional group by introducing an unnatural amino acid, p-azidophenylalanine, into the FP structure. ...
Redox reactions play a key role in maintaining essential biological processes. Deviations in redox pathways result in the development of various pathologies at cellular and organismal levels. Until recently, studies on transformations in the intracellular redox state have been significantly hampered in living systems. The genetically encoded indicators, based on fluorescent proteins, have provided new opportunities in biomedical research. The existing indicators already enable monitoring of cellular redox parameters in different processes including embryogenesis, aging, inflammation, tissue regeneration, and pathogenesis of various diseases. In this review, we summarize information about all genetically encoded redox indicators developed to date. We provide the description of each indicator and discuss its advantages and limitations, as well as points that need to be considered when choosing an indicator for a particular experiment. One chapter is devoted to the important discoveries that have been made by using genetically encoded redox indicators.
... 1 The prevalence of type 2 diabetes mellitus in India was 51 million people in 2010. 2 In contrast to its role as poison, hydrogen sulfide (H 2 S) is considered as the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO). [3][4][5] Though it was first reported in 1982 that it is produced in mammalian tissues, but only now it has emerged as a mediator of important physiologic functions in humans. 6 Experimental evidences have been published implicating H 2 S overproduction as a causative factor in the pathogenesis of β-cell death in diabetes. ...
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Background : Diabetes mellitus is a major health problem not only in India but worldwide. Our country presently is undergoing an epidemic stage of this non-communicable disease.Though several etiological background of type 2 diabetes has been well explained, yet a number of recent literatures suggested a potential role H<sub>2</sub>S producing enzymes in the etiology and management of this metabolic disorder.
Aims and Objectives: Our aim was to elucidate the relationship of H<sub>2</sub>S synthesizing activity in plasma and fasting blood glucose in type 2 diabetic patients.
Materials and Methods: Sixty-two newly diagnosed type 2 diabetes patients and equal number of non-diabetic controls were included in the study. Enzymatic activity of synthesizing H<sub>2</sub>S in plasma was estimated following methods described earlier with further modification and standardization in our laboratory. All other parameters were estimated by using standardized kits.
Results: FBG, PPBG, HbA<sub>1C</sub>, Fasting Insulin, H<sub>2</sub>S synthesizing activity in plasma in patients are significantly higher (p < 0.05) than the corresponding values in healthy controls H<sub>2</sub>S synthesizing activity in plasma is positively correlated with fasting plasma glucose and the correlations is significant(p=0.05).
Conclusion: Our study though a pilot study with a small sample size, has elucidated that the values of H<sub>2</sub>S synthesizing activity in plasma are significantly elevated in type 2 diabetic patients and this may help researchers to develop H<sub>2</sub>S modifying agents and enzyme inhibitors which may open up new horizon in the treatment modalities of type 2 diabetes mellitus.
Asian Journal of Medical Sciences Vol.7(6) 2016 6-10
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... In recent years, more attention has been directed towards H 2 S as the third gaseous mediator, which has been shown to exhibit vasodilatory activity both in vitro and in vivo. 5 Of the three enzymes, cystathionine-g-lyase, cystathionine-b-synthetase and 3-mercaptopyruvate sulfurtransferase, can utilize L-cysteine as a substrate to produce H 2 S. 6 Dysfunction of H 2 S-producing enzymes results in physiological disorders such as homocystinuria, which is characterized by mental retardation, skeletal abnormalities, increased urine homocysteine, increased risks of thromboembolism, and early onset of atherosclerosis. 7,8 H 2 S was also found to prevent vascular remodeling from endothelial damage and was shown to regulate vascular tone and angiogenesis via S-sulfhydration of the potassium channel. ...
Background:
Hydrogen sulfide (H2S) is one of the endogenous gaseous molecules promoting the production of nitric oxide (NO) which has cardioprotective functions. However, the role of the H2S-mediated protein S-nitrosoproteome and its subsequent physiological response remains unclear.
Methods:
Endothelial cells EAhy 926 were treated with 50 μM of H2S for 2 hours. The NO bound S-nitrosoproteins were purified by a biotin-switch and then digested by trypsin. Resulting peptides from control and H2S treatment were separately labeled by isobaric tag for relative and absolute quantitation 114/115, quantified by liquid chromatography tandem-mass spectrometry and analyzed by ingenuity pathway analysis (IPA) software. The microP software was applied to analyze the morphological changes of mitochondria.
Results:
With the treatment of H2S, 416 S-nitrosylated proteins were identified. IPA analysis showed that these proteins were involved in five signaling pathways. The NO-bound cysteine residues and the S-nitrosylation levels (115/114) were shown for ten S-nitrosoproteins. Western blot further verified the S-nitrosylation of thioredoxin-dependant peroxide reductase, cytochrome c oxidase and cytochrome b-c1 complex that are involved in the mitochondrial signaling pathway. H2O2-induced mitochondrial swelling can be reduced by the pretreatment of H2S.
Conclusions:
The H2S-mediated endothelial S-nitrosoproteome has been confirmed. In the present study, we have proposed the cardioprotective role of H2S via maintaining mitochondrial homeostasis.
... While arginine catabolism might contribute to nitric oxide (NO) homeostasis, additional vasodilation mechanisms can possibly be explained by decreased levels of taurine/hypotaurine ( Figure 5) together with cysteine consumption (Figure 4) to mirror altered function of H 2 S-generating pathways. 51 Direct measurements of hydrogen sulfide (H 2 S) showed significant decreases after exposure to high altitude hypoxia, and H 2 S levels remained significantly lower than baseline values during the second reascent (p<0.0001 - Figure 5). ...
Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated. Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters. Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and maintained for 16 days at high altitude. Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism. Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic memory.
... Hydrogen sulfide (H 2 S), besides its poisonous effects mainly on mitochondrial electron transport chain, is considered as the third gasotransmitter after (NO) and carbon monoxide (CO). [2][3][4] Though it was first reported in 1982 that it is produced in mammalian tissues, but now recognized as a mediator with important physiologic functions in humans. 5 H 2 S is formed in vivo from L-cysteine by enzymes, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), both require pyridoxal-5-phosphate as cofactor. ...
Background:
Diabetes mellitus, a worldwide health problem, is associated with increased oxidative stress and reduced antioxidant defense in the body. The role of hydrogen sulfide and the H2S synthesizing enzymes in relation to type2 diabetes is a recently unveiled field which needs further research work.
Aims and Objectives:
Aim of the study was find out the relationship of plasma H2S levels and H2S synthesizing activity in plasma with oxidative stress conditions in the patients suffering from type-2 diabetes mellitus.
Materials and Methods:
Sixty two patients suffering from type2 diabetes as well as similar number of healthy volunteers were enrolled for the study. Plasma H2S levels and H2S synthesizing activity in plasma as well as total oxidative stress and total antioxidant levels were measured by earlier methods already published from our laboratory.
Results:
The values of FBG, PPBG, HbA1C, fasting Insulin, plasma H2S and H2S synthesizing activity in plasma and TOS values in patients are significantly higher (p< 0.05) than the corresponding values in healthy controls. The median and inter quartile range of TAD values in controls is significantly higher than those of the patients (Mann Whitney U, Z
... Sulfide (H 2 S, HS 2 and S 22 ) is produced during the synthesis and breakdown of sulfur-containing amino acids in plants, animals and microorganisms (Singh and Banerjee, 2011). It is a signalling molecule (Wagner, 2009), targeting redox sensors and heme groups in human and animal models (Olson, 2011), and regulating photosynthesis in cyanobacteria (Klatt et al., 2015). It also functions as a universal defense against antibiotics through its spontaneous reaction with reactive oxygen species (Shatalin et al., 2011). ...
Many heterotrophic bacteria contain sulfide:quinone oxidoreductase (SQR) and persulfide dioxygenase (PDO) genes. It is unclear how these enzymes cooperate to oxidize sulfide in bacteria. Cupriavidus pinatubonensis JMP134 contains a gene cluster of sqr and pdo, and their functions were analyzed in Escherichia coli. Recombinant E. coli cells with SQR and PDO rapidly oxidized sulfide to thiosulfate and sulfite. The SQR also contains a DUF442 domain that was shown to have rhodanese activities. E. coli cells with PDO and SQR-C94S, an active site mutant of the rhodanese domain, oxidized sulfide to thiosulfate with transitory accumulation of polysulfides. Cellular and enzymatic evidence showed that DUF442 speeds up the reaction of polysulfides with glutathione to produce glutathione persulfide (GSSH). Thus, SQR oxidizes sulfide to polysulfides; rhodanese enhances the reaction of polysulfides with glutathione to produce GSSH; PDO oxidizes GSSH to sulfite; sulfite spontaneously reacts with polysulfides to generate thiosulfate. The pathway is different from the proposed mitochondrial pathway because it has polysulfides, i.e., disulfide and trisulfide, as intermediates. The data demonstrated that heterotrophic bacteria with SQR and PDO can rapidly oxidize sulfide to thiosulfate and sulfite, providing the foundation for using heterotrophic bacteria with SQR and PDO for sulfide bioremediation. This article is protected by copyright. All rights reserved.
... Blackstone, Morrison et al. 2005; Blackstone and Roth 2007) en le comparant à un s sontpharmacologique. Les souris ont un métabolisme 15 à 20 fois supérieur au la thermogénèse non-induite par les frissons (nonshivering thermogenesis) liée à 2 S pourrait avoir un effet métabolique direct chez le gros mammifère(Wagner 2009;Derwall, Francis et al. 2011;Wagner, Georgieff et al. 2011). ...
Ischemia/reperfusion (I/R) is a very common phenomenon, observed during intestinal artery surgery, shock treatment, as well as in several other diseases. The disruption of tissue perfusion (ischemia) and recovery (reperfusion) induce hemodynamic and metabolic dysfunction. Gut ischemia/reperfusion is often presented as the main source of lactate and the motor of the inflammatory response, such as cardiogenic, hypovolemic and septic shock. In parallel, gut reperfusion produces numerous mediators such as reactive oxygen metabolites, pro-inflammatory cytokines, and high concentrations of nitric oxide.
In a model of ischemia/reperfusion induced by hemorrhagic shock, we found that 1) NaHS an injectable form of H2S, limited the decrease in arterial pressure induced by shock and decreased plasmatic lactate, a witness of tissue suffering, 2) this hemodynamic improvement was associated with a fall in myocardial iNOS mRNA expression, a reduction in the concentration of plasmatic NOx and a reduction of aortic and myocardial concentrations of NO and superoxide anion and 3) the inhibition of H2S with DL-propargylglycine worsened hemodynamics and tissue consequences of shock
An experimental model of intestinal I/R has been developed, we demonstrated that the administration of APC or Dexa : 1) Improves MAP and vascular reactivity, 2) increased pH and decreased lactate, 3) decreased pro-inflammatory cytokines production and 4) inhibited apoptosis mediators expression. These results are related to a down regulation of iNOS, to a restoration of the AKT/eNOS pathway, and to alpha-adrenoreceptor resensitization.
These results open new perspectives in clinical treatment of I/R.
... This increase in blood pressure and increased plasma levels of Ang II and NA may be the casual factors for the reduction in CSE mRNA and CSE activity in the heart and corresponding decrease in H 2 S concentrations in both plasma and heart. This view can be supported by the report that deletion of cystathione γ lyase is associated with the development of hypertension in mice [50] and H 2 S produced from CSE is known as a vasorelaxant and blood pressure regulator [51]. Reduction in CSE activity after administration of isoproterenol in present study is in line with the previous reported data [41]. ...
Hydrogen sulphide (H2S) is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH) is unknown. The present study explored the effect of exogenous H2S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE) in the myocardium. Animals were divided into four groups: Control, LVH, Control-H2S and LVH-H2S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C) and caffeine in drinking water (62mg/L) for 2 weeks. Intraperitoneal NaHS, 56μM/kg/day for 5 weeks, was given as an H2S donor. Myocardial expression of Cystathione γ lyase (CSE) mRNA was quantified using real time polymerase chain reaction (qPCR).There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H2S and LVH-H2S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P
... При этом CBS осуществляет синтез сероводорода преимущественно в нервных клетках . В гладкомышечных клетках кровеносных сосудов, сокращение и расслабление которых обеспечивает изменение тонуса последних, синтез сероводорода осуществляет фермент CSE [10, 11], а в эндотелиальных клетках, выстилающих изнутри просвет сосуда, — 3MST [12, 13]. Все 3 фермента используют в качестве субстрата для синтеза сероводорода серосодержащую аминокислоту L-цистеин, катализируя реакцию его десульфгидратации: происходит отщепление от цистеина атома серы без последующего его окисления, что ведет к образованию H 2 S. Под действием CSE происходит преобразование цистина (дисульфид цистеин) до тиоцистеина, пирувата и аммиака с последующим неферментативным преобразованием тиоцистеина до цистеина и H 2 S. В то же время CBS использует несколько другой путь синтеза H 2 S, который заключается в конденсации гомоцистеина с цистеином и последующем образовании цистатионина [10]. ...
... These gaseous inorganic compounds, unlike other biologically active molecules, easy to penetrate through the membrane of any cells, do not bind with any receptor on the surface of cells and interact directly with intracellular proteins [2]. Among the so kind known metabolic regulators, so far H 2 S the least studied [3]. ...
... It is an early indicator of the development of the micro-and macroangiopathy associated with diabetes (Triggle and Ding, 2010). Substitution of H 2 S protects against the development of endothelial dysfunction (Szabo, 2007;Wagner, 2009;Asdaq and Inamdar, 2010). The paracrine (vasocrine) H 2 S signaling into the artery wall may represent a potential therapeutic target for obesity-and diabetes-associated vascular dysfunction. ...
The aim of our study is to clarify the contribution of cystathionine gamma-lyase (CSE) that produces H2S in smooth muscle and perivascular adipose tissues in the regulation of resistance size rat artery contraction. In this research the isometric contraction of de-endothelised rat gracilis artery preparations was measured with Small Vessel Myograph (DMT 410M, Denmark). Half of the isolated rings were incubated in 20 mmol/l D-glucose-containing bath and the others in normal glucose solution (5.5 mmol/l). Increasing concentrations of serotonin (5-hydroxytryptamine) from 10-10 to 10-5 mmol/l were applied to induce gradual constriction of circular artery segments. The absence of endothelium was confirmed by the lack of the relaxation to acetylcholine. The extra cellular glucose concentration of 20 mmol/l did not influence the contractile effect of serotonin. The inhibition of CSE by DL-propargyl glycine significantly enhanced the maximal force of serotonin-induced contraction under normal and hyperglycemic conditions. It is concluded that CSE is an important regulator of endothelium denuded rat resistance arteries. It is suggested that CSE in smooth muscle cells of artery wall released mediator that antagonized the constricting action of serotonin. This regulation is insensitive to extra cellular glucose concentration.
... More recently, hydrogen peroxide (H 2 O 2 ) and hydrogen sul de (H 2 S) have been highlighted in vascular research as important mediators in the relaxant response of di erent vessels. 17,18 us, the discovery of these molecules in vascular function opens a relevant eld on the therapeutic potential of thromboembolic disease. ...
Aerobic exercise promotes beneficial effects on the prevention and treatment of diseases such as arterial hypertension, atherosclerosis, venous insufficiency, and peripheral arterial disease. β-adrenergic receptors are present in a variety of cells. In the cardiovascular system, β-adrenergic receptors promote positive inotropic and chronotropic response and vasorelaxation. Although the effect of exercise training has been largely studied in the cardiac tissue, studies focused on the vascular tissue are rare and controversial. This review examines the data from studies using animal and human models to determine the effect of physical exercise on the relaxing response mediated by β-adrenergic receptors as well as the cellular mechanisms involved in this response. Studies have shown reduction, increase, or no effect of physical exercise on the relaxing response mediated by β-adrenergic receptors. Thus, the effects of exercise on the vascular β-adrenergic sensitivity should be more deeply investigated. Furthermore, the physiopathology of the vascular system is an open field for the discovery of new compounds and advances in the clinical practice.
... При этом CBS осуществляет синтез сероводорода преимущественно в нервных клетках. В гладкомышечных клетках кровеносных сосудов, сокращение и расслабление которых обеспечивает изменение тонуса последних, синтез сероводорода осуществляет фермент CSE [10,11], а в эндотелиальных клетках, выстилающих изнутри просвет сосуда, -3MST [12,13]. ...
The data offoreign studies over the last 15 years devoted to endogenous synthesis and biological role of hydrogen sulfide in micromolar quantities which complemented the already two well-known gas transmitters - OH and NO are presented in this review. Despite the short period since the physiological properties of hydrogen sulfide were opened (about 20 years) it was found that this gas transmitter plays a key role in the regulation of nerve (neural signal transmission), cardiovascular (relaxation of smooth muscles), immune (antinflammatory and cytoprotective agent) sensory, gastrointestinal (output of insulin) systems and in the metabolism of various organs. Currently the role of H2S in the pathogenesis of different diseases, neurodegenerative diseases, diabetes, heart failure) is being studying. The developments of drugs that act as either exogenous donors H2S or blockers of the biosynthesis of H2S are promising. With consideration the fact that H2S is a representative of non-synaptic way of intercellular communication based on diffusion of molecules of inorganic compounds in the intercellular space in all directions and effect on distant from their place offormation non- synaptic receptors it is suggested to use exogenous H2S in strict proportion for the treatment of a number of human diseases.
Hypertension is a major public health problem globally. It is the most common cause of cardiovascular morbidities and mortalities, with a negative impact on renal function. Uncontrolled hypertension causes chronic kidney disease, which progresses to end-stage renal disease and eventually loss of renal function. Unfortunately, the mechanism underlying the pathogenesis of hypertension and its associated nephropathy is still poorly understood. Also worrying is the fact that despite conventional antihypertensive therapies, achievement of blood pressure control and preservation of renal function still remain a worldwide public health challenge in a significant subpopulation of hypertensive patients. This suggests the need for novel pharmacotherapeutic approaches to curb the problem. Hydrogen sulfide (H2S), the third established member of the gasotransmitter family after nitric oxide and carbon monoxide, has been recognized and established to possess antihypertensive and renoprotective properties, which may represent an important therapeutic alternative for hypertensive nephropathy. In this chapter, recent findings from preclinical studies about the therapeutic effect of H2S against hypertensive nephropathy and its future clinical use are discussed. A section of the chapter also discusses recent developments about clinical and translational research on calcium-based nephrolithiasis as a risk factor for hypertensive nephropathy, with a further discussion on H2S as an emerging novel therapy to improve clinical outcome.
In this paper, we demonstrate real-time hydrogen sulfide monitoring in liquid using a flexible inkjet printed Ag/rGO/Nafion-Ru(NH
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two-electrode amperometric sensor. The electrodes are inkjet-printed on a flexible substrate, Kapton film, where silver nanoparticles (Ag NPs) are printed as conductive electrodes. The working and reference electrodes are printed Ag/rGO/Nafion-Ru(NH
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<sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6<sup>3+/2+</sup></sub>
and Ag/AgCl
<sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(s)</sub>
/PU layers respectively. The as-printed sensor exhibits a linear sensitivity of 40 nA/μM/cm
<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup>
(R=99.7%) and a LoD of 0.75 μM in the range of 1 to 120 μM. The sensor shows the tendency of increase and saturation of the hydrogen sulfide released from cysteine in heating eggs indicating the effectiveness of the sensor for real-time monitoring.
Правові засади розуміння механізму адміністративно-правового регулювання
Обман як підстава визнання господарського договору недійсним
This chapter introduces luminescence responsive chemical sensing of anions by rare earth metal-organic framework (MOF) hybrid materials. Compared to cation analytes, reports on luminescent sensing of anions via rare earth MOF hybrid materials are not abundant, except for Cr(VI) oxysalts. There are two typical kinds of anions, the complicated oxysalt group of ions and simple halogen ions or pseudohalogen ions. Herein four sections discuss: (1) rare earth MOF hybrid materials for luminescence responsive chemical sensing of fluoride ions (F⁻); (2) rare earth MOF hybrid materials for luminescence responsive chemical sensing of other simple anions (S2 −, HS⁻, and SCN⁻); (3) rare earth MOF hybrid materials for luminescence responsive chemical sensing of main group element oxysalt anions; (4) rare earth MOF hybrid materials for luminescence responsive chemical sensing of transition metal oxysalts anions.
Oxidative stress (OS) is characteristic of a diverse set of physiological and pathophysiological states. For example, human health problems associated with oxidative stress include Parkinson’s disease, Alzheimer’s disease, myocardial infarction, cancer, diabetes, various inflammations, renal failure, and atherosclerosis as well as aging. It has become routine and convenient to screen body fluids, including blood (serum or plasma), saliva, and urine, as well as exhaled breath for small molecules that are biomarkers of oxidative stress to ascertain the oxidative stress status (OSS) of a particular targeted organ or the whole body. Unfortunately, circulating levels of oxidation products and/or antioxidants often do not truly represent the tissue/organ/whole body state of oxidative stress or antioxidant status due to the diverse nature of oxidative reactions, metabolic status, and tissue retention. Hence, the analyst has to bear several important points in mind while ascertaining the state of oxidative stress or antioxidant status by measuring one or two chosen biomarkers in one or two selected sampling sites at any given time.
Acid-sensing ion channels (ASICs) have been implicated in many physiological and patho-physiological processes like synaptic plasticity, inflammation, pain perception, stroke-induced brain damage and, drug-seeking behaviour. Although ASICs have been shown to be modulated by gasotransmitters like nitric oxide (NO), their regulation by hydrogen sulfide (H2S) is not known. Here, we present strong evidence that H2S potentiates ASICs-mediated currents. Low pH-induced current in Chinese hamster ovary (CHO) cells, expressing homomeric either ASIC1a, ASIC2a or ASIC3, increased significantly by an H2S donor NaHS. The effect was reversed by washing the cells with NaHS-free external solution of pH 7.4. MTSES, a membrane impermeable cysteine thiol-modifier failed to abrogate the effect of NaHS on ASIC1a, suggesting that the target cysteine residues are not in the extracellular region of the channel. The effect of NaHS is not mediated through NO, as the basal NO level in cells did not change following NaHS application. This previously unknown mechanism of ASICs-modulation by H2S adds a new dimension to the ASICs in health and disease.
Researches focused on the chemical biology of endogenous hydrogen polysulfide (H2Sn, n > 1) is rapidly growing since H2Sn potentially playing crucial roles in many physiological activities. Herein, by taking advantage of the unique H2Sn, but not H2S or biothiols, mediated substitution-cyclization reaction cascade, we have developed a novel fluorescent probe, C-HPS, for highly selective detection of H2Sn over H2S or biothiols. Upon addition of H2Sn, C-HPS displayed remarkable fluorescence enhancement (up to 97 folds) at 576 nm with rapid response time (within 6 min) and adequate sensitivity (LOD = 20 nM). Besides, the application of C-HPS to visualize intracellular H2Sn was also demonstrated in living MGC-803 cells.
In this paper, Bio-MOF-1 is prepared as reported and then Eu³⁺ is introduced into it via cation exchange method. A FAM-labeled ssDNA is chosen to fabricate with the obtained Eu³⁺@Bio-MOF-1. A luminescent hybrid material is assembled, which can exhibit the fluorescence of Eu³⁺ and FAM simultaneously by adjusting the ratio of FAM-ssDNA and Eu³⁺@Bio-MOF-1. The sample is then used for the detecting of metal ions, results shows which has good selectively for Cu²⁺ (LOD = 0.14 μM, 0–250 μM). The introduction of Cu²⁺ can quench the fluorescence of FAM while the luminescent intensity of Eu³⁺ enhancing. After the detection of Cu²⁺, the Cu²⁺ involved hybrid system can then be further employed for the detection of S²⁻ (LOD = 1.3 μM, 0–50 μM). Low concentration of S²⁻ can make the luminescent intensity of Eu³⁺ decrease gradually while high concentration of S²⁻ can further recover the luminescent of FAM, which is quenched by Cu²⁺.
Objectives:
There is increasing interest in hydrogen sulphide as a marker of pathologic conditions or predictors of outcome. We speculate that as hydrogen sulphide is a diffusible molecule, if there is an increase in plasma hydrogen sulphide in sepsis, it may accumulate in the alveolar space and be detected in exhaled gas. "We wished to determine whether we could detect hydrogen sulphide in exhaled gases of ventilated children and neonates and if the levels changed in sepsis."
Design:
Prospective, observational study.
Setting:
The study was conducted across three intensive care units, pediatric, neonatal and cardiac in a large tertiary children's hospital.
Patients:
We studied ventilated children and neonates with sepsis, defined by having two or more systemic inflammatory response syndrome criteria and one organ failure or suspected infection. A control group of ventilated non-septic patients was also included.
Intervention:
A portable gas chromatograph (OralChroma; Envin Scientific, Chester, United Kingdom) was used to measure H2S in parts per billion.
Measurements and main results:
A 1-2 mL sample of expired gas was taken from the endotracheal tube and analyzed. A repeat sample was taken after 30 minutes and a further single daily sample up to a maximum of 5 days or until the patient was extubated. WBC and C-reactive protein were measured around the time of gas sampling. Each group contained 20 subjects. Levels of H2S were significantly higher in septic patients (Mann Whitney U-test; p < 0.0001) and trended to control levels over five days. C-reactive protein levels were also significantly raised (p < 0.001) and mirrored the decrease in H2S levels.
Conclusion:
Hydrogen sulphide can be detected in expired pulmonary gases in very low concentrations of parts per billion. Significantly higher levels are seen in septic patients compared with controls. The pattern of response was similar to that of C-reactive protein.
Cysteine catabolism presents cells with a double-edged sword. On the one hand, cysteine degradation provides cells with essential molecules such as taurine and sulfide. The formation of sulfide in cells is thought to regulate important and diverse physiological processes including blood circulation, synaptic activity and inflammation. On the other hand, the catabolism of cysteine by gut microbiota can release high levels of sulfide that may underlie the development or relapse of ulcerative colitis, an inflammatory bowel disease affecting millions of people worldwide. Here, we have used the nematode C. elegans to explore how cells tolerate high levels of sulfide produced by cysteine degradation in bacteria. We have identified mutations in genes coding for thioredoxin family proteins, mitochondrial proteins, and collagens that confer tolerance to sulfide toxicity. Exposure to sulfide induces the unfolded protein response in the endoplasmic reticulum and mitochondria. Moreover, our results suggest that sulfide toxicity is mediated by reactive oxygen species (ROS). Indeed, pre-treatment of worms with antioxidants increases their tolerance to sulfide toxicity. Intriguingly, sub-toxic levels of the superoxide generator paraquat can also increase the tolerance of worms to sulfide. Therefore, it appears that activation of ROS detoxification pathway prior to the exposure to sulfide, can increase the tolerance to sulfide toxicity. Our results suggest that these detoxification pathways are mediated by the hypoxia inducible factor HIF-1. Finally, we show that sulfide resistance varies among wild C. elegans and other nematode species, suggesting that tolerance to sulfide was naturally selected in certain habitats.
Influence of gasotransmitters carbon monoxide (CO) and hydrogen sulfide (H2S) on the electrical and contractile activities of smooth muscle cells (SMCs) of the guinea pig ureter and rat aorta were studied by methods of double sucrose bridge and mechanography. It has been shown that CO causes a dose-dependent decrease of the contractile response of SMCs of the ureter and rat aorta and also reduces the amplitude and duration of the action potential plateau. Against the background of the action of biologically active substances, agonists α1-adrenergetic and H1-histaminergetic receptors (phenylephrine and histamine, respectively), these effects of CO donor (CORM II) were amplified. The inhibitory effect of CO on the parameters of the contractile and electrical activities of smooth muscles is attenuated by blocking potassium channels of plasma membrane with tetraethylammonium (TEA) or inhibition of soluble guanylate cyclase (ODQ [1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-l-one]). Thus, the effects of carbon monoxide on the electrical and contractile activities of SMCs are associated with an increase potassium conductivity of the membrane or the activation of soluble guanylate cyclase.In experiments with a donor of hydrogen sulfide (NaHS), it was shown, that it has an activating effect on the electrical and contractile activities of smooth muscles of the guinea pig ureter, which is caused by the action of potassium conductivity of the membrane. Activating effect of H2S on the contractile properties of SMCs of the guinea pig ureter decreased by blocking ATP-dependent channels with glibenclamide. Analysis of the effect of H2S on sodium and calcium conductance of the membrane smooth muscles of the ureter using modified sodium-free and TEA- containing Krebs solution showed that the contribution of potassium conductance is mainly sold at high concentrations (100 and 1000 μmol) donor NaHS. Probably, that the impact of low concentrations of NaHS (10 μmol) on the amplitude of contractions SMCs of the ureter and performed through the activation of the calcium component of the action potential. It was shown, that activating effect of NaHS determined by involving sodium-dependent ion transporters to cAMP-dependent inhibition of potassium conductance membranes of smooth muscles.
The development of an embryo is instructed by the vast information encoded in the genome. Transactions of information contained in the DNA direct the system-wide spatial and temporal changes of numbers and cell types that ultimately impart specific phenotypes to organs/tissues and body plans. The salient outcomes of the development of the lung are proper formation of airways and blood vessels. Optimal geometry and dimensions of these conduits allow efficient transport of the respiratory fluid media (air and blood) while granting large respiratory surface area, thin blood–gas (tissue) barrier, and large pulmonary capillary blood volume, foremost features that determine the diffusing capacity of the lung for O2. The extensive surface area is achieved by the process of branching morphogenesis (BM) (e.g., Bewig et al. 1997; Metzger et al. 2008; Affolter et al. 2009; Warburton et al. 2010; Yates et al. 2010; Morrisey and Hogan 2010). Saxena and Sariola (1987) termed it (BM) as “growth and branching of epithelial buds” where in sequence a preceding branch generates two daughter branches (Fig. 4.1), ultimately generating functional systems (airway, arterial, and venous) that closely pattern each other and intimately relate to optimize respiratory surface area and minimize diffusion distance (Fig. 4.2).
Reconstruction of the changes that have occurred during the evolution of the gas exchangers is riddled with pitfalls. This is mainly because of the almost complete lack of instructive fossilized materials, as would be expected, of soft tissues such as the respiratory organs/structures. The precept that “progeny recapitulates phylogeny” is too simple for the discipline of evolutionary developmental biology (evo–devo) to be directly extrapolated in studies of the paleobiology of respiration (e.g., Northcutt 1990). For example, during their development (metamorphosis), amphibians undergo drastic changes in the form, location, and function of the gas exchangers (Sect. 5.4.1). The transformations cannot be predicted from one level of development to another. Moreover, respiration appears to be too important for perpetuation of “primitive” features from one evolutionary level to another.
Der akute Lungenschaden (acute lung injury, ALI) stellt aufgrund der schlechten Behandlungsmöglichkeiten ein großes Problem in der Intensivmedizin dar. Die Auslöser des ALI sind vielfältig. Sowohl Entzündung als auch oxidativer Stress, welcher oftmals durch eine therapeutische Sauerstoffgabe verstärkt wird, spielen in der Pathogenese eine wichtige Rolle. Experimentelle Daten der letzten Jahre deuten zunehmend auf die antioxidativen und antiinflammatorischen Eigenschaften des Gasotransmitters Schwefelwasserstoff (H2S) hin. Die Effekte von exogen zugeführtem H2S auf den Lungenschaden oxidativer oder inflammatorischer Genese sind weitestgehend ungeklärt und wurden in dieser Arbeit anhand zweier Mausmodelle untersucht:
1) Bei einem Hyperoxie-induzierten ALI konnte gezeigt werden, dass die Verabreichung des H2S-Donators Natriumshydrogensulfid den Lungenschaden reduzieren konnte. Diese Aussage stützt sich auf die beobachtete Verminderung des histologisch nachweisbaren ALIs und eine Reduktion der Gesamtproteinmenge und Zellzahl in der bronchoalveolären Lavage, die als Biomarker für den oxidativen Lungenschaden dienten. Der protektive Effekt wird vermutlich über eine Reduktion der reaktiven Sauerstoffspezies durch H2S und eine Abnahme des Signalmoleküls Angiopoietin 2 vermittelt.
2) Ein durch Lipopolysaccharid induziertes inflammatorisches ALI wurde durch Inhalation des gasförmigen H2S behandelt. Anhand der Verminderung des histologischen Gewebeschadens, der Transmigration neutrophiler Zellen und der Freisetzung der proinflammatorischen Zytokine Interleukin-1 ß und Macrophage Inflammatory Protein-2, zeigte H2S auch in dieser Versuchsserie einen lungenprotektiven Effekt. Dieser könnte über die verminderte Expression der mitogen aktivierten Proteinkinase p38 vermittelt sein, die nachfolgend zu einer Reduktion der Rekrutierung neutrophiler Zellen in die Lunge führen und dadurch den inflammatorischen Prozess hemmen könnte.
3) Die Lipopolysaccharidinstillation führte zu einem Anstieg des H2S-Syntheseenzyms Cystathionin-ß-Synthetase, das durch H2S deutlich reduziert wurde. Dieser Befund lässt auf eine Substrathemmung von exogenem H2S auf die endogene Synthese schließen.
Studies of nitric oxide over the past two decades have highlighted the fundamental importance of gaseous signaling molecules
in biology and medicine. The physiological role of other gases such as carbon monoxide and hydrogen sulfide (H2S) is now receiving increasing attention. Here we show that H2S is physiologically generated by cystathionine γ-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces
H2S levels in the serum, heart, aorta, and other tissues. Mutant mice lacking CSE display pronounced hypertension and diminished
endothelium-dependent vasorelaxation. CSE is physiologically activated by calcium-calmodulin, which is a mechanism for H2S formation in response to vascular activation. These findings provide direct evidence that H2S is a physiologic vasodilator and regulator of blood pressure.
Nitric oxide (NO) is produced in almost all tissues and organs, exerting multiple biological actions under both physiological and pathological conditions. NO is synthesized by three different isoforms of NO synthase (NOS): neuronal, inducible, and endothelial NOSs. Due to the substantial compensatory interactions among the NOS isoforms, the ultimate roles of endogenous NO in our body still remain to be fully elucidated. To address this point, we have successfully developed mice in which all three NOS genes are completely disrupted. NOS expression and activities were totally absent in the triply n/i/eNOS(-/-) mice before and after treatment with lipopolysaccharide. While the triply n/i/eNOS(-/-) mice were viable, their survival and fertility rates were markedly reduced as compared with wild-type mice. The phenotypes of those mice that we first noticed were polyuria, polydipsia, and renal unresponsiveness to vasopressin, characteristics consistent with nephrogenic diabetes insipidus. We subsequently observed that in those mice, arteriosclerosis is spontaneously developed with a clustering of cardiovascular risk factors. These results provide the first evidence that the systemic deletion of all three NOSs causes a variety of cardiovascular diseases in mice, demonstrating a critical role of the endogenous NOSs system in maintaining cardiovascular homeostasis.
Hydrogen sulphide (H2S) is increasingly being recognized as an important signalling molecule in the cardiovascular and nervous systems. The production of H2S from L-cysteine is catalysed primarily by two enzymes, cystathionine gamma-lyase and cystathionine beta-synthase. Evidence is accumulating to demonstrate that inhibitors of H2S production or therapeutic H2S donor compounds exert significant effects in various animal models of inflammation, reperfusion injury and circulatory shock. H2S can also induce a reversible state of hypothermia and suspended-animation-like state in rodents. This article overviews the physiology and biochemistry of H2S, summarizes the effects of H2S inhibitors or H2S donors in animal models of disease and outlines the potential options for the therapeutic exploitation of H2S.
The consumption of garlic is inversely correlated with the progression of cardiovascular disease, although the responsible mechanisms remain unclear. Here we show that human RBCs convert garlic-derived organic polysulfides into hydrogen sulfide (H2S), an endogenous cardioprotective vascular cell signaling molecule. This H2S production, measured in real time by a novel polarographic H2S sensor, is supported by glucose-maintained cytosolic glutathione levels and is to a large extent reliant on reduced thiols in or on the RBC membrane. H2S production from organic polysulfides is facilitated by allyl substituents and by increasing numbers of tethering sulfur atoms. Allyl-substituted polysulfides undergo nucleophilic substitution at the α carbon of the allyl substituent, thereby forming a hydropolysulfide (RSnH), a key intermediate during the formation of H2S. Organic polysulfides (R-Sn-R′; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RSnH and H2S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H2S. The vasoactivity of garlic compounds is synchronous with H2S production, and their potency to mediate relaxation increases with H2S yield, strongly supporting our hypothesis that H2S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H2S can be used to standardize garlic dietary supplements.
• Allium
• aorta
• polysulfides
• red blood cells
• vasorelaxation
Nitric oxide, which is produced endogenously within cardiac myocytes by three distinct isoforms of nitric oxide synthase, is a key regulator of myocardial function. This review will focus on the regulation of myocardial function by each nitric oxide synthase isoform during health and disease, with a specific emphasis on the proposed end-targets and signaling pathways.
Hydrogen sulfide, like nitric oxide, was best known as a toxic pollutant before becoming recognized as a key regulator of several physiologic processes. In recent years, evidence has accumulated to suggest important roles for hydrogen sulfide as a mediator of several aspects of gastrointestinal and liver function. Moreover, alterations in hydrogen sulfide production could contribute to disorders of the gastrointestinal tract and liver. For example, nonsteroidal anti-inflammatory drugs can reduce production of hydrogen sulfide in the stomach, and this has been shown to contribute to the generation of mucosal injury. Hydrogen sulfide has also been shown to play a key role in modulation of visceral hyperalgesia. Inhibitors of hydrogen sulfide synthesis and drugs that can generate safe levels of hydrogen sulfide in vivo have been developed and are permitting interventional studies in experimental models and, in the near future, humans.
Nitric oxide (NO) and carbon monoxide (CO) synthesized from L-arginine by NO synthase and from heme by heme oxygenase, respectively, are the well-known neurotransmitters and are also involved in the regulation of vascular tone. Recent studies suggest that hydrogen sulfide (H(2)S) is the third gaseous mediator in mammals. H(2)S is synthesized from L-cysteine by either cystathionine beta-synthase (CBS) or cystathionine gamma-lyase (CSE), both using pyridoxal 5'-phosphate (vitamin B(6)) as a cofactor. H(2)S stimulates ATP-sensitive potassium channels (K(ATP)) in the vascular smooth muscle cells, neurons, cardiomyocytes and pancreatic beta-cells. In addition, H(2)S may react with reactive oxygen and/or nitrogen species limiting their toxic effects but also, attenuating their physiological functions, like nitric oxide does. In contrast to NO and CO, H(2)S does not stimulate soluble guanylate cyclase. H(2)S is involved in the regulation of vascular tone, myocardial contractility, neurotransmission, and insulin secretion. H(2)S deficiency was observed in various animal models of arterial and pulmonary hypertension, Alzheimer's disease, gastric mucosal injury and liver cirrhosis. Exogenous H(2)S ameliorates myocardial dysfunction associated with the ischemia/reperfusion injury and reduces the damage of gastric mucosa induced by anti-inflammatory drugs. On the other hand, excessive production of H(2)S may contribute to the pathogenesis of inflammatory diseases, septic shock, cerebral stroke and mental retardation in patients with Down syndrome, and reduction of its production may be of potential therapeutic value in these states.
The past two decades have seen an upsurge in interest in the biology of naturally occurring gases, starting with nitric oxide and extending through to carbon monoxide. The latest addition to the list of biologically relevant gases is hydrogen sulfide. In the past few years, hydrogen sulfide has transited rapidly from environmental pollutant to biologically relevant mediator with potential roles in several physiological processes and disease states. Further, interest is now being shown in developing drugs which either mimic its effects or block its biosynthesis. Similarly to its gaseous cousins, the biology of hydrogen sulfide is proving to be complex and difficult to unravel.
Hydrogen sulfide mediates the vasoactivity of garlic Received: January 27
- Ga Benavides
- Gl Squadrito
- Mills
- Rw
Benavides GA, Squadrito GL, Mills RW, et al. Hydrogen sulfide mediates the vasoactivity of garlic. Proc Natl Acad Sci U S A. 2007;104:17977-17982. Received: January 27, 2009 Accepted: February 05, 2009 © Società Italiana di Nefrologia JN_D_09_00010_Wagner.indd 176 14-04-2009 15:30:23