Philip G Board's research while affiliated with Australian National University and other places
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Publications (220)
Although many breast cancer therapies show initial success in the treatment of the primary tumour, they often fail to eliminate a sub-population of cells known as cancer stem cells (CSCs). These cells are recognised for their self-renewal properties and for their capacity for differentiation often leading to chemo/radio-resistance. The antiviral dr...
Background:
Reports on the prognostic significance of serum γ-glutamyltransferase (GGT) in men with metastatic castration-resistant prostate cancer (mCRPC) are limited. In addition, GGT expression status in cancer tissues has not been well characterized regardless of cancer types.
Methods:
This retrospective study included 107 consecutive men wi...
γ-Glutamyltransferase (GGT), a membrane-bound enzyme, contributes to the metabolism of glutathione (GSH), which plays a critical physiological role in protecting cells against oxidative stress. GGT has been proposed as a biomarker of carcinogenesis and tumor progression given that GGT activity is important during both the promotion and invasion pha...
Inflammatory bowel disease (IBD) is characterized by multiple alterations in cytokine expression and is a risk factor for colon cancer. The Omega class glutathione transferase GSTO1-1 regulates the release of the pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18) by deglutathionylating NEK7 in the NLRP3 inflammasome. When...
Drug metabolizing enzymes catalyze the biotransformation of many of drugs and chemicals. The drug metabolizing enzymes are distributed among several evolutionary classes and catalyze a range of detoxication reactions, including oxidation/reduction, conjugative, and hydrolytic reactions that serve to detoxify potentially toxic compounds. This detoxi...
Backgroundγ-Glutamyltransferase (GGT) is a marker of oxidative stress. Elevated serum GGT is linked to poor survival in various malignancies; however, there are no data on metastatic renal cell carcinoma (mRCC). Additionally, GGT expression in cancer tissues remains largely unknown.Objective
The present study was designed to determine the prognosti...
Glutathione transferase omega-1 (GSTO1-1) is an enzyme whose function supports the activation of IL-1β and IL-18 that are implicated in a variety of inflammatory disease states for which small-molecule inhibitors are sought. The potent reactivity of the active site cysteine has resulted in reported inhibitors that act by covalent labelling. In this...
Background:
Glutathione S-Transferases Omega Class 1 (GSTO1-1) is a unique member of the GST family regulating cellular redox metabolism and innate immunity through the promotion of LPS/TLR4/NLRP3 signaling in macrophages. House Dust Mite (HDM) triggers asthma by promoting Type 2 responses and allergic inflammation via the TLR4 pathway. Although l...
The NLRP3 inflammasome is a cytosolic complex sensing phagocytosed material and various damage-associated molecular patterns, triggering production of the pro-inflammatory cytokines interleukin-1 beta (IL)-1β and IL-18 and promoting pyroptosis. Here, we characterize glutathione transferase omega 1-1 (GSTO1-1), a constitutive deglutathionylating enz...
Background
Cation transport regulator 1 (CHAC1), a newly discovered enzyme that degrades glutathione, is induced in Helicobacter pylori (H. pylori)‐infected gastric epithelial cells in culture. The CHAC1‐induced decrease in glutathione leads to an accumulation of reactive oxygen species and somatic mutations in TP53. We evaluated the possible corre...
Purpose:
Glutathione-S-transferase omega 1-1 (GSTO1-1) is a cytosolic glutathione transferase enzyme, involved in glutathionylation, toll-like receptor signaling, and calcium channel regulation. GSTO1-1 dysregulation has been implicated in oxidative stress and inflammation, and contributes to the pathogenesis of several diseases and neurological d...
Early-stage drug discovery reporting on relatively new or difficult targets is often associated with insufficient hit triage. Literature reviews of such targets seldom delve into the detail required to critically analyze the associated screening hits reported. Here we take the enzyme GSTO1-1 as an example of a relatively difficult target and review...
Fig. S1. Reactivity of the novel monoclonal antibody to CHAC1.
Fig. S2. The levels of CHAC1 mRNA, GSH, ROS and CHAC1 protein in H. pylori‐infected samples used for mutation analysis.
Table S1. Primers and probes used for this study.
Table S2. CHAC1 overexpression leading to TP53 mutation in AGS cells (results from each of the two experiments)....
Infection with Helicobacter pylori is known to decrease the level of glutathione in gastric epithelial cells and increase the production of reactive oxygen species (ROS), which can lead to DNA damage and the development of gastric cancer. Cation transport regulator 1 (CHAC1) has γ-glutamylcyclotransferase activity that degrades glutathione. We foun...
The glutathione (GSH) transferases remain one of the most thoroughly understood group of detoxication enzymes. The structures and regulatory aspects of the genes encoding the canonical enzymes are as well understood as any. Their involvement in the biotransformation of many endogenous and xenobiotic electrophiles is well understood at the enzymolog...
Glutathione transferase Omega 1 (GSTO1-1) is an atypical GST reported to play a pro-inflammatory role in response to LPS. Here we show that genetic knockout of Gsto1 alters the response of mice to three distinct inflammatory disease models. GSTO1-1 deficiency ameliorates the inflammatory response stimulated by LPS and attenuates the inflammatory im...
Ryanodine receptor (RyR) calcium channels are central to striated muscle function and influence signalling in neurones and other cell types. Beneficially low RyR activity and maximum conductance opening may be stabilised when RyRs bind to FK506 binding proteins (FKBPs) and destabilised by FKBP dissociation, with submaximal opening during RyR hypera...
Background
Helicoverpa armigera and Helicoverpa zea are major caterpillar pests of Old and New World agriculture, respectively. Both, particularly H. armigera, are extremely polyphagous, and H. armigera has developed resistance to many insecticides. Here we use comparative genomics, transcriptomics and resequencing to elucidate the genetic basis fo...
Significance
Toll-like receptor (TLR) signaling pathways are targeted to limit inflammation in immune cells. TLRs use adaptor proteins to drive inflammatory signaling platforms for effective microbial clearance. Here we show that MyD88 adaptor-like (MAL), an adaptor protein in TLR signaling, undergoes glutathionylation in response to LPS, driving m...
Excitation-contraction (EC) coupling in skeletal muscle requires a physical interaction between the voltage-gated calcium channel dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR1) Ca2+ release channel. Although the exact molecular mechanism that initiates skeletal EC coupling is unresolved, it is clear that both the ?1s and ? subuni...
Ryanodine receptor (RyR) ion channels are essential for skeletal and cardiac muscle function. Their knockout leads to perinatal death from respiratory and cardiac failure. Acquired changes or mutations in the protein cause debilitating skeletal myopathy and cardiac arrhythmia which can be deadly. Knowledge of the pharmacology of RyR channels is cen...
The cardiac ryanodine receptor (RyR2) is an intracellular ion channel that regulates Ca 2+ release from the sarcoplasmic reticulum (SR) during excitation–contraction coupling in the heart. The glutathione transferases (GSTs) are a family of phase II detoxification enzymes with additional functions including the selective inhibition of RyR2, with th...
The Omega-class cytosolic glutathione transferases (GSTs) have distinct structural and functional attributes that allow them to perform novel roles unrelated to the functions of other GSTs. Mammalian GSTO1-1 has been found to play a previously unappreciated role in the glutathionylation cycle that is emerging as significant mechanism regulating pro...
Cisplatin is an effective anticancer drug; however, cisplatin use often leads to nephrotoxicity, which limits its clinical effectiveness. In this study, we determined the effect of dichloroacetate, a novel anticancer agent, in a mouse model of cisplatin-induced AKI. Pretreatment with dichloroacetate significantly attenuated the cisplatin-induced in...
Background and aim:
While gender differences in hepatocellular carcinoma (HCC) are profound, the mechanism is unclear. Using castration and hormone replacement strategies, we tested whether these gender differences are attributable to testosterone or estradiol/progesterone (E/P) effects on cell cycle regulators and p53.
Methods:
We studied dyspl...
Release of Ca(2+) from the sarcoplasmic reticulum (SR) through the cardiac ryanodine receptor (RyR2) is an essential step in cardiac excitation-contraction coupling. Excess Ca(2+) release due to overactive RyR2 can cause arrhythmia that can lead to cardiac arrest. Fragments derived from the carboxy-terminal domain of human glutathione transferase M...
Although excitation-contraction (EC) coupling in skeletal muscle relies on physical activation of the skeletal ryanodine receptor (RyR1) Ca(2+) release channel by dihydropyridine receptors (DHPRs), the activation pathway between the DHPR and RyR1 remains unknown. However, the pathway includes the DHPR β1a subunit which is integral to EC coupling an...
Macrophages mediate innate immune responses that recognise foreign pathogens, and bacterial lipopolysaccharide (LPS) recruits a signalling pathway through Toll-like receptor 4 (TLR4) to induce pro-inflammatory cytokines and reactive oxygen species (ROS). LPS activation also skews the metabolism of macrophages towards a glycolytic phenotype. Here, w...
Ryanodine receptor (RyR) Ca2+ release channels located in the membrane of sarcoplasmic reticulum Ca2+ stores provide the Ca2+ required for contraction in skeletal muscle and the heart. The normal function of the ion channels is necessary for optimal muscle function. Increases in channel activity in relaxed muscle lead to increased cytoplasmic Ca2+,...
Bacterial lipopolysaccharide (LPS) stimulation of macrophages and inflammation via the Toll-like receptor 4 (TLR4) signalling pathway through NFκΒ generates reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-1β, IL-6 and TNFα. Since GSTO1-1 can catalyze redox reactions such as the deglutathionylation of proteins and has also be...
There is a continuing need to improve the efficacy of anticancer agents and to reduce the toxicity associated with them. Recently, reversal of the glycolytic phenotype of cancer cells with novel agents such as DCA (dichloroacetate) has been recognised as an important new target for cancer therapy. DCA is currently being assessed as a novel chemothe...
There is an overwhelming body of work supporting the idea that excitation-contraction coupling in skeletal muscle depends on a physical interaction between the skeletal muscle isoform of the dihydropyridine receptor L-type Ca(2+) channel and the skeletal isoform of the ryanodine receptor Ca(2+) release channel. A general assumption is that this phy...
Recently, overexpression of γ-glutamylcyclotransferase (GGCT) has been reported in various cancer tissues suggesting that it has significant potential as a diagnostic marker. The aim of this study was to examine the suitability of GGCT for the detection of high-risk lesions at an early stage of esophageal squamous cell carcinoma (ESCC). A total of...
The glutathionylation of intracellular protein thiols can protect against irreversible oxidation and can act as a redox switch
regulating metabolic pathways. In this study we discovered that the Omega class glutathione transferase GSTO1-1 plays a significant
role in the glutathionylation cycle. The catalytic activity of GSTO1-1 was determined in vi...
Glutathione transferases (GSTs) are protection enzymes capable of conjugating glutathione (GSH) to toxic compounds. During evolution an important catalytic cysteine residue involved in GSH activation was replaced by serine or, more recently, by tyrosine. The utility of these replacements represents an enigma because they yield no improvements in th...
Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reac...
Sarcopenia is characterised by reduced muscle mass and reduced force that is only partially attributable to muscle atrophy. Fiber type distribution changes with aging (fast twitch decreases, slow twitch increases). Excitation-contraction coupling (ECC) may be impaired by an uncoupling of the dihydropyridine receptor (DHPR) and the ryanodine recepto...
Accumulating evidence shows that glutathione peroxidase (GPX, EC.1.11.1.9), one of the most important antioxidant selenoenzymes, plays an essential role in protecting cells and tissues against oxidative damage by catalyzing the reduction of hydrogen peroxide by glutathione. Unfortunately, because of the limited availability and poor stability of GP...
Background:
The cytosolic glutathione transferases (GSTs) comprise a super family of proteins that can be categorized into multiple classes with a mixture of highly specific and overlapping functions.
Scope of review:
The review covers the genetics, structure and function of the human cytosolic GSTs with particular attention to their emerging ro...
This study reports the development of a new assay for the rapid determination of protein glutathionylation in tissues and cell lines using commercially available reagents and standard instrumentation. In this method cells are homogenized in the presence of N-ethylmaleimide to eliminate free thiols and the proteins are precipitated with acetone. Sub...
Excitation-contraction (EC) coupling in skeletal muscle depends on protein interactions between the transverse tubule dihydropyridine receptor (DHPR) voltage sensor and intracellular ryanodine receptor (RyR1) calcium release channel. We present novel data showing that the C-terminal 35 residues of the β(1a) subunit adopt a nascent α-helix in which...
Chloride intracellular channel 2 (CLIC2) protein is a member of the glutathione transferase class of proteins. Its' only known function is the regulation of ryanodine receptor (RyR) intracellular Ca(2+) release channels. These RyR proteins play a major role in the regulation of Ca(2+) signaling in many cells. Utilizing exome capture and deep sequen...
S-Glutathionyl-hydroquinone reductases (GS-HQRs) are a new class of glutathione transferases, widely present in bacteria, halobacteria, fungi, and plants. They catalyze glutathione (GSH)-dependent reduction of GS-trichloro-p-hydroquinone to trichloro-p-hydroquinone. Since GS-trichloro-p-hydroquinone is uncommon in nature, the extensive presence of...
Glutathione peroxidase (GPX) is a crucial antioxidant selenocysteine (Sec) containing enzyme which plays a significant role in protecting cells against oxidative damage by catalyzing the reduction of hydroperoxides with glutathione (GSH). Several methods have been used to generate GPX mimics, however, only a few of these methods involved genetic en...
While genetic testing for familial cancer susceptibility factors has excelled in recent years, the prevention options for those carrying high risk alleles have not. Altered bioenergetics has now been acknowledged as an emerging hallmark of cancer, and is believed to be a critical characteristic acquired during tumorigenesis. Several very safe drugs...
The muscle-specific glutathione transferase GSTM2-2 modulates the activity of ryanodine receptor (RyR) calcium release channels: it inhibits the activity of cardiac RyR (RyR2) channels with high affinity and activates skeletal RyR (RyR1) channels with low affinity. The C terminal domain of GSTM2-2 (GSTM2C) alone physically binds to RyR2 and inhibit...
Excitation-contraction (EC) coupling in skeletal muscle proceeds in the absence of an influx of external calcium ions. This suggests that there is a physical interaction between the dihydropyridine receptor (DHPR) voltage sensor in the surface/transverse tubule membrane and the skeletal muscle ryanodine receptor (RyR1) calcium release channel in th...
The glutathione transferase (GST) super family of enzymes catalyze the conjugation of glutathione (GSH) to a wide range of exogenous and endogenous compounds. In addition to catalytic reactions, the GSTs also modulate several cell signaling kinases and ion channels such as Jun N‐terminal kinase and ryanodine receptors via protein /protein interacti...
γ-Glutamylcyclotransferase (GGCT) is a component of the γ-glutamyl cycle and specifically cleaves γ-glutamyl-amino acid dipeptides to release the free amino acid and 5-oxoproline. The action of GGCT in glutathione synthetase-deficient patients results in the accumulation of high levels of 5-oxoproline. In addition, GGCT may be a biomarker in some c...
γ-Glutamyl cyclotransferase (GGCT) contributes to the γ-glutamyl cycle that regulates glutathione metabolism. Although GGCT has been implicated in several studies as a possible cancer marker, little is known about its distribution in cells and tissues. The authors investigated GGCT expression in normal tissues and tumors using Western blots and imm...
Dichloroacetic acid (DCA) has potential for use in cancer therapy and the treatment of metabolic acidosis. However, DCA can create a deficiency of glutathione transferase Zeta (GSTZ1-1). Gstz1 knockout mice have elevated oxidative stress and low glutathione levels that increases their sensitivity to acetaminophen toxicity. As it is highly likely th...
Cancer cells have a different metabolic profile compared to normal cells. The Warburg effect (increased aerobic glycolysis) and glutaminolysis (increased mitochondrial activity from glutamine catabolism) are well known hallmarks of cancer and are accompanied by increased lactate production, hyperpolarized mitochondrial membrane and increased produc...
Complete set of identified RyR1 single-particles incubated with anti-SPRY2 antibodies presenting additional mass (indicated by white arrows). Unprocessed RyR1 particles incubated with the specified anti-SPRY2 antibody (anti-SPRY2-A, anti-SPRY2-B, anti-SPRY2-C; upper row), and calculated 2D projections (bottom row) for RyR1 containing four 30 Å radi...
The type 1 skeletal muscle ryanodine receptor (RyR1) is principally responsible for Ca(2+) release from the sarcoplasmic reticulum and for the subsequent muscle contraction. The RyR1 contains three SPRY domains. SPRY domains are generally known to mediate protein-protein interactions, however the location of the three SPRY domains in the 3D structu...
Glutathione transferase kappa (GSTK1-1) is a highly conserved, mitochondrial enzyme potentially involved in redox reactions. GSTK1-1-deficient mice were generated to further study the enzyme's biological role. Reduced and total glutathione levels in liver and kidney were unchanged by GSTK1-1 deficiency and NADPH quinone oxidoreductase 1 expression...
A key component of excitation contraction (EC) coupling in skeletal muscle is the cytoplasmic linker (II-III loop) between
the second and third transmembrane repeats of the α1S subunit of the dihydropyridine receptor (DHPR). The II-III loop has been previously examined in vitro using a linear II-III loop with unrestrained N- and C-terminal ends. To...
The omega class of glutathione transferases (GSTs) is a relatively ancient member of the cytosolic GST superfamily, and the omega-class GSTs are found in plants, animals, and some microbial species. The omega-class GSTs exhibit the canonical GST fold, but, unlike other GSTs, the omega-class GSTs have a cysteine residue in their active site. Consequ...
It has recently emerged that glutathione transferase enzymes (GSTs) and other structurally related molecules can be translocated from the external medium into many different cell types. In this study we aim to explore in detail, the structural features that govern cell translocation and by dissecting the human GST enzyme GSTM2-2 we quantatively dem...
The second of three SPRY domains (SPRY2, S1085 -V1208) located in the skeletal muscle ryanodine receptor (RyR1) is contained within regions of RyR1 that influence EC coupling and bind to imperatoxin A, a toxin probe of RyR1 channel gating. We examined the binding of the F loop (P1107-A1121) in SPRY2 to the ASI/basic region in RyR1 (T3471-G3500, con...
Glutathione transferase zeta (GSTZ1) is a member of the GST superfamily of proteins that catalyze the reaction of glutathione with endo- and xenobiotics. GSTZ1-1 was discovered by a bioinformatics strategy that searched the human-expressed sequence-tag database with a sequence that matched a putative plant GST. A sequence that was found was express...
The ryanodine receptor (RyR) is an ion channel that releases Ca2þ from the sarcoplasmic reticulum and is essential for excitation-contraction coupling and
contraction in striated muscle. Previously we reported that the human muscle
specific glutathione transferase (GSTM2-2) is an inhibitor of cardiac muscle
RyR2 and a weak activator of skeletal mus...
Although it has been suggested that the C-terminal tail of the β(1a) subunit of the skeletal dihyropyridine receptor (DHPR) may contribute to voltage-activated Ca(2+) release in skeletal muscle by interacting with the skeletal ryanodine receptor (RyR1), a direct functional interaction between the two proteins has not been demonstrated previously. S...
The polymorphic deletion of Glu-155 from human glutathione transferase omega1 (GSTO1-1) occurs in most populations. Although the recombinant ΔGlu-155 enzyme expressed in Escherichia coli is active, the deletion causes a deficiency of the active enzyme in vivo. The crystal structure and the folding/unfolding kinetics of the ΔGlu-155 variant were det...
Glutathione transferases (GSTs) are generally recognized for their role in phase II detoxification reactions. However, it is becoming increasingly apparent that members of the GST family also have a diverse range of other functions that are, in general, unrelated to detoxification. One such action is a specific inhibition of the cardiac isoform of...
Ca(2+) release from the sarcoplasmic reticulum through cardiac ryanodine receptors (RyR2) is essential for heart function and is inhibited by the carboxy terminal domain of glutathione transferase M2-2 (GSTM2-C) and derivative fragments containing helix 6. Since a peptide encoding helix 6 alone does not fold into a helix and does not inhibit RyR2 C...
Sphingobium chlorophenolicum completely mineralizes PCP (pentachlorophenol). Two GSTs (glutathione transferases), PcpC and PcpF, are involved in the degradation. PcpC uses GSH to reduce TeCH (tetrachloro-p-hydroquinone) to TriCH (trichloro-p-hydroquinone) and then to DiCH (dichloro-p-hydroquinone) during PCP degradation. However, oxidatively damage...
γ-Glutamylamine cyclotransferase (GGACT) is an enzyme that converts γ-glutamylamines to free amines and 5-oxoproline. GGACT
shows high activity toward γ-glutamyl-ϵ-lysine, derived from the breakdown of fibrin and other proteins cross-linked by transglutaminases.
The enzyme adopts the newly identified cyclotransferase fold, observed in γ-glutamylcyc...
The level of glutathione transferase Kappa (GSTK1-1) has been correlated with obesity (Liu et.al. 2008 PNAS 105: 18302-7) and a polymorphism in the hGSTK1 promoter has been associated with insulin secretion and fat deposition (Gao et al 2009 Endocr J 56: 487-94). We searched for additional polymorphisms that may influence GSTK1-1 function or expres...
Dichloroacetate (DCA) has recently been proposed as a novel and relatively non-toxic anticancer agent that can reverse the glycolytic phenotype in cancer cells through the inhibition of pyruvate dehydrogenase kinase. Over 90% of all tumours show an increased glycolysis and this response could contribute to tumour progression, metastasis and resista...
Dichloroacetate (DCA) has recently been proposed as a novel non-toxic anticancer agent that can reverse the glycolytic phenotype in cancer cells through the inhibition of pyruvate dehydrogenase kinase.
Aims and Methods
Three mouse cancer cell lines (V14, 4T1 and B16) were used to examine the histological changes caused by DCA in vivo. V14 or 4T1 m...
Prostaglandin D(2) synthesised by the hematopoietic prostaglandin D(2) synthase has a pro-inflammatory effect in allergic asthma, regulating many hallmark characteristics of the disease. Here we describe identification of hematopoietic prostaglandin D(2) synthase inhibitors including cibacron blue, bromosulfophthalein and ethacrynic acid. Expansion...
The glycolytic phenotype is a widespread phenomenon in solid cancer forms, including breast cancer. Dichloroacetate (DCA) has recently been proposed as a novel and relatively non-toxic anti-cancer agent that can reverse the glycolytic phenotype in cancer cells through the inhibition of pyruvate dehydrogenase kinase. We have examined the effect of D...
Glutathione transferase Zeta (GSTZ1-1) is identical to maleylacetoacetate isomerase and catalyses a significant step in the catabolism of phenylalanine and tyrosine. Exposure of GSTZ1-1 deficient mice to high dietary phenylalanine causes a rapid loss of circulating white blood cells (WBCs). The loss was significant (P<0.05) after 2 days and total W...
The muscle specific glutathione transferase GSTM2-2 inhibits the activity of cardiac ryanodine receptor (RyR2) calcium release channels with high affinity and activates skeletal RyR (RyR1) channels with lower affinity. To determine which overall region of the GSTM2-2 molecule supports binding to RyR2, we examined the effects of truncating GSTM2-2 o...
Glutathione transferases are a family of enzymes that are traditionally known to contribute to the phase II class of detoxification reactions. However, a novel property of the Schistosoma japonicum glutathione transferase (Sj.GST26) involves its translocation from the external medium into a variety of different cell types. Here we explore the effic...
Citations
... Antiviral drugs show antiproliferative and cytotoxic effects on various cancer cells, including BC [34], without inducing toxicity to normal cells. Previously, some antiviral drugs have also been effective against TNBC by targeting self-renewal, EMT, and gene expression in CSCs [35]. Nucleoside analogs are classic chemotherapeutic drugs that are extensively used in adjuvant therapy [36]. ...
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... GGT has been extensively studied and is widely used as a biomarker in clinical practice (142)(143)(144). Serum GGT activity is a rapid, reliable and cost-effective method to assess liver function (145). Therefore, GGT has the potential to serve as a tumor biomarker. ...
... 49 Moreover, it has been shown that the protein GSTM1 is also absent in 30% and 50% of patients with UC and colon adenocarcinoma, respectively, that harbor a GSTM1 þ genotype, 50 demonstrating that this enzyme is also regulated posttranscriptionally. Although numerous redundant GTSs exist, the deletion of Gsto1 in mice is associated with susceptibility to DSS colitis 51,52 and to AOM-DSS-induced tumorigenesis. 52 Reciprocally, the local delivery of the Gstt1 gene to mice treated with DSS dampens colitis. ...
... The first mechanism by which GSTs can confer resistance is direct detoxification. Foreign compounds can be made less reactive by conjugation with glutathione, reducing their toxicity (Board and Anders 2021). The second mechanism by which GSTs confer resistance is inhibition of the mitogen-activated protein. ...
... Among most often reported in the literature biochemical predictive indices we have chosen for evaluation 10 biomarkers focusing on easily obtained parameters known to be associated with chronic systemic diseases, in particular CVDs/IHD and osteoporosis, and being factors allowing modification. The battery of these serum biomarkers included: parathyroid hormone (PTH) [44][45][46][47][48][49][50][51][52][53][54][55], vitamin D [51,[56][57][58][59][60][61][62][63], albumin, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78], Urea [79][80][81][82][83][84][85][86][87][88][89][90], GGT/ALT ratio [51,[91][92][93][94][95], GGT/Albumin ratio [96,97], Urea/Albumin ratio [98][99][100][101][102] and Platelets/Albumin ratio [103,104]. ...
... Various aliphatic, aromatic, and heterocyclic compounds were studied as non-covalent and covalent inhibitors of GSTs. 5 Among them the derivatives and structural analogues of α-fluoromethylhistidine, 6 benzenesulfonamide, 7 benzisoselenazolone, 8 dichlorotriazine, 9 piperlongumine, 10 as well as glutathione [11][12] have been recently investigated. It was shown that ethacrynic acid and its analogues are able to inhibit GSTP1-1. ...
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... This study uncovers a significant and causal association between GSTO1 and childhood asthma, where increased levels of genetically determined GSTO1 are linked to an elevated risk of developing this condition. [35][36][37] Other studies have demonstrated that inhibiting GSTO1-1 using shRNA in LPS-exposed macrophages reduces the activation of interleukin (IL)-1β, IL-6, and NLRP3 ...
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... inflammasomes. 38 Additionally, using GSTO1-1-deficient mice in inflammatory disease models supported these in vitro findings, showing decreased expression levels of IL-1β, IL-6, and TNF-α in LPS-induced inflammation compared to wild-type (WT) controls. These findings suggest a potential role of GSTO1 in promoting asthma development through the induction of inflammatory responses and damage to airway epithelial cells. ...
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... Infection with H. pylori triggers ChaC1 overexpression in gastric epithelial cells, leading to GSH degradation and ROS accumulation, suppressing nucleotide alterations in TP53 that induce tumor suppressor gene expression (130). Overexpression of ChaC1 in H. pylori-infected parietal cells may also lead to H. pylori-induced somatic mutation, thereby promoting the development of gastric cancer (131). In summary, high expression of human ChaC1 is involved in inducing development of gastric cancer. ...
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... CD14 + monocytes or mouse lung sections were fixed and stained with primary antibodies against LC3, ASC, and TFEB or isotype controls, as described. [32][33][34] Immunofluorescence quantification and image acquisition were performed as described. [32][33][34][35] ...
