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C-phycocyanin alleviated mitochondrial morphology changes induced by OGD/R. The mitochondrial morphology of H9c2 cells was visualized by mitochondrion-selective probe Mito-Tracker. Cells were treated with C-pc (0, 10, 20, and 40 μg/ml) or phosphate-buffered saline (PBS) and subjected to OGD/R except the control group. Representative images showed the morphology of mitochondria (scale bar 20 μm). The images in the dotted box are shown at a higher resolution on the below. The white arrow showed the diminutive and globular mitochondria, and the blue arrow showed filamentous mitochondria.
Source publication
Mitochondrial dysfunction is a predominant risk factor in ischemic heart disease, in which the imbalance of mitochondrial fusion and fission deteriorates mitochondrial function and might lead to cardiomyocyte death. C-phycocyanin (C-pc), an active component from blue-green algae, such as Spirulina platensis, has been reported to have anti-apoptosis...
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Citations
... Recent studies revealed the existence of bidirectional regulatory mechanisms. C-Phycocyanin (C-Pc), an active ingredient extracted from blue-green algae, inhibits the OGD/R-induced overexpression of DRP1, thereby enhancing the expression of MFN1/2 and OPA1 and effectively protecting cardiomyocytes from ischemic injury (Gao 2019). This suggests that mitochondrial kinetic homeostasis has great potential for regulating mitochondrial remodeling and treating mitochondrial disorder-related diseases. ...
Mitochondria serve as the primary site for metabolizing the three major nutrients, underscoring their pivotal role in cellular energy metabolism and the regulation of signaling pathways. Mitochondrial homeostatic imbalance is a key pathological cause of the development of many diseases. Hence, preserving mitochondrial homeostasis is vital for the normal growth and development of cells and organisms. Living organisms have evolved intricate regulatory mechanisms to ensure cellular mitochondrial homeostasis. This review focuses on recent advancements in comprehending the mechanisms responsible for maintaining mitochondrial homeostasis and addresses the current challenges in this field. We also provide an overview of the key functions of mitochondria in both physiological and pathological conditions. Emphasizing the potential therapeutic implications, we discuss strategies for preserving mitochondrial homeostasis, recognizing its significance in mitigating various health conditions.
Graphical Abstract
... Furthermore, substances used in health treatments, such as Doxorubicin, a potent antineoplastic agent, can have associated risk of developing cardiomyopathy and congestive heart failure. The cardiotoxicity of doxorubicin is also associated with oxidative stress and apoptosis (6). ...
Objective: To perform a systematic review on using Cyanobacteria for protecting the cardiac tissue against damage caused by ischemia.Methods: this review encompasses in vitro and controlled animal experimental studies.Results: the results show that in general there are two types of interventions for treatment of ischemia and Ischemia/Reperfusion (IR) in cardiac tissue: (1) extracts treatments and (2) injection of Cyanobacteria in the damaged tissues. Extract treatments are based on the antioxidant potential of Cyanobacteria, and the studies focus mainly on Spirulina (Arthrospira platensis). The direct injection methods are based on the high capacity of these organisms to release oxygen during photosynthesis. Synechococcus elongatus is the Cyanobacteria species most commonly utilized in injections, either delivered independently or carried by hydrogels or nanoparticles. The direct Cyanobacteria injections are innovative techniques which can promote protection against apoptosis and have shown promising results, however, further research is necessary to refine the techniques and improve overall efficacy.Conclusion: the effects of these treatments were beneficial considering that the antioxidant effects of Cyanobacteria ameliorate blood biochemical markers and reduce damaged cardiac areas. The oxygen releasing of Cyanobacteria in the cardiac tissue also promoted recovery of cardiac tissue after ischemia or IR.
... Mitochondrial dysfunction increases the probability of stress response and transcription factor ATF4, which causes a modification of the CCO enzyme and induces morphological changes in the mitochondria, which results in reduced mitochondrial activity and glucose metabolism [18,48]. Mitochondrial dysfunction is elicited by the imbalance between the mitochondrial fusion proteins, like Opa1, Mfn1 and Mfn2 (which are decreased) and fission proteins like Drp1, Fis1, Mff and Mief (which are elevated) [49][50][51] and also includes mitochondrial enzymes provoked metabolic dysfunctions [52] are also involved in the development of AD [53,54]. PBMT was known to reinstate the mitochondrial activity and to maintain the mitochondrial homeostasis [42,55]. ...
Aim: Photobiomodulation involves the use of low-level light therapy or near-infrared light therapy found to be useful in the treatment of a wide range of neurological diseases. Objective: The aim is to review the mechanism and clinical applications of photobiomodulation therapy (PBMT) in managing Alzheimer's disease. Methods: To ensure that the consensus statement accurately reflects both the experts' viewpoint and the most recent developments in the field, the expert opinions were recorded and thoroughly reviewed. Results: PBMT elicits reduction of beta-amyloid plaque, restoration of mitochondrial function, anti-inflammatory and antioxidant properties with a stimulation in ATP synthesis. Conclusion: The PBMT could be helpful in patients non-responsive to traditional pharmacological therapy providing significant aid in the management of Alzheimer's disease when introduced into the medical field.
... Cytochrome c (Cyt C), positioned at the interface of IMM and OMM, can be effectively retained within the mitochondria through the actions of OPA1 and Mfns. Drp1 aggregates on the OMM under different pressures and interacts with Bax to facilitate the translocation of pro-apoptotic proteins such as Cyt C and AIF into the cytoplasm, as well as activating the critical downstream effector protease caspase-3 in the apoptotic pathway, triggering apoptosis mediated by the mitochondria [56][57][58]. Previous studies revealed that Cr(VI) induces mitochondrial dynamics disorders and abnormal expression of apoptosis-related factors, as evidenced by the increasing mRNA and protein expression of mitochondrial-mediated apoptosis, such as Cyt C, Bax, and caspase-3, as well as Bcl-2 and the Bcl-2/Bax ratio in liver tissues and cardiomyocytes [47,59]; this is consistent with our results. ...
Hexavalent chromium (Cr(VI)) is a hazardous substance that poses significant risks to environmental ecosystems and animal organisms. However, the specific consequences of Cr(VI) exposure in terms of liver damage remain incompletely understood. This study aims to elucidate the mechanism by which Cr(VI) disrupts mitochondrial dynamics, leading to hepatic injury in ducks. Forty-eight healthy 8-day-old ducks were divided into four groups and subjected to diets containing varying doses of Cr(VI) (0, 9.28, 46.4, and 232 mg/kg) for 49 days. Our results demonstrated that Cr(VI) exposure resulted in disarranged liver lobular vacuolation, along with increasing the serum levels of ALT, AST, and AKP in a dose-dependent manner, which indicated liver damage. Furthermore, Cr(VI) exposure induced oxidative stress by reducing the activities of T-SOD, SOD, GSH-Px, GSH, and CAT, while increasing the contents of MDA and H2O2. Moreover, Cr(VI) exposure downregulated the activities of CS and MDH, resulting in energy disturbance, as evidenced by the reduced AMPK/p-AMPK ratio and PGC-1α protein expression. Additionally, Cr(VI) exposure disrupted mitochondrial dynamics through decreased expression of OPA1, Mfn1, and Mfn2 and increased expression of Drp-1, Fis1, and MFF proteins. This disruption ultimately triggered mitochondria-mediated apoptosis, as evidenced by elevated levels of caspase-3, Cyt C, and Bax, along with decreased expression of Bcl-2 and the Bcl-2/Bax ratio, at both the protein and mRNA levels. In summary, this study highlights that Cr(VI) exposure induces oxidative stress, inhibits the AMPK-PGC-1α pathway, disrupts mitochondrial dynamics, and triggers liver cell apoptosis in ducks.
... Cardiomyocytes account for the highest proportion of the various types of cells that make up the heart, and they are rich in myofibrils and mitochondria [3]. In patients with hypertension complicated with IR, due to high blood pressure and glucose metabolism disorders, cardiomyocytes overconsume ATP while overload operations, and mitochondrial homeostasis is destroyed, thus leading to oxidative stress and mitochondrial dynamic abnormalities [4], that is, the mitochondria divide from a reticular structure in a normal state into a fragment-like structure, eventually triggering apoptosis of the mitochondrial pathway in cardiomyocytes. At present, it is difficult to recover the normal function of mitochondria. ...
To explore the effect of acacetin on myocardial mitochondrial dysfunction in spontaneously hypertensive rats (SHR) with insulin resistance (IR), and the possible mechanism. Rapid IR was first induced in fructose-fed SHR, and they were then treated with acacetin (25, 50 mg/kg). After 7 weeks, the rats were tested for hypertension, IR, cardiac function, and mitochondrial damage status. Potential mechanisms of action were explored in terms of oxidative stress, mitochondrial fission and division, apoptosis, and the insulin signaling pathway. Subsequently, the PI3K gene was silenced, after intervention with acacetin (5 μM) for 24 h, and H2O2 was used to stimulate H9c2 for 4 h, it was evaluated whether silencing PI3K would affect the therapeutic effect of acacetin. In SHR fed with fructose, acacetin can improve hypertension, IR, cardiac function (LVEF, LVFS), and mitochondrial damage (mitochondria number, ATP); inhibit oxidative stress (ROS, SOD, Nrf2, Keap1), mitochondrial fission (MFF, Drp1), and myocardial cell apoptosis (apoptosis rate, Bax, Bcl-2, cytochrome c); promote mitochondrial fusion (Mfn2) and activate insulin signaling pathways (PI3K/AKT). However, silencing PI3K inhibited the abovementioned effects of acacetin. In conclusion, acacetin improved myocardial mitochondrial dysfunction through regulating oxidative stress, mitochondrial fission and fusion, and mitochondrial pathway apoptosis mediated by PI3K/AKT signaling pathway in hypertensive rats with IR.
... Several studies showed that C-phycocyanin has beneficial effects on the development of porcine parthenos by attenuating mitochondrial dysfunction and oxidative stress. C-phycocyanin prevented the H 2 O 2 -induced compromise of mitochondrial membrane potential, release of cytochrome c from the mitochondria, and ROS generation [24,25]. Thus, it is to explore whether the inhibition of mitochondrial disruption may relate to the anti-apoptotic effect of R-PC and its impact on mitochondrial permeability in the presence of H 2 O 2 using the JC-1 assay. ...
Aging has become a global public health challenge. Many studies have revealed that the excessive generation of ROS and oxidative stress could be the major causative factors contributing to aging. In this study, R-phycocyanin (R-PC) was isolated from Porphyra haitanensis, and its anti-aging ability was explored by natural aging Drosophila melanogaster and H2O2-induced HUVEC cells as the aging model. Results showed that R-PC α and β subunits expressed have antioxidant activity and can inhibit the generation of radicals, exhibiting a protective effect against H2O2-induced apoptotic HUVEC cells death. R-PC prevented the H2O2-induced HUVEC cell cycle phase arrest by regulating cell cycle-related protein. Furthermore, R-PC prevented the H2O2-induced HUVEC cell cycle phase arrest by regulating cell-cycle-related protein expression. In vivo study also indicated that R-PC significantly increased the survival time and alleviated the oxidative stress of Drosophila melanogaster. Moreover, R-PC notably decreased levels of ROS in natural aging flies and inhibited lipid peroxidation by enhancing the expressions of the endogenous stress marker genes (SOD1, SOD2, CAT of Drosophila melanogaster). Taken together, a study on the antioxidation extract from Porphyra haitanensis, such as R-PC, may open a new window for the prevention of anti-aging.
... C-Phycocyanin has been used as an antioxidant and anti-inflammatory treatment for its structure and pharmacological security, avoiding oxidative stress and cell damage (Romay et al. 2003). It has been reported as neuroprotective (Rimbau et al. 1999;Romay et al. 2003), nephroprotective (Rodr ıguez-S anchez et al. 2012Memije-Lazaro et al. 2018;Rojas-Franco et al. 2018, hepatoprotective (Sathyasaikumar et al. 2007;Ou et al. 2010), as well in fact the C-phycocyanin prevents oxidative stress and cell damage in vitro as the hypoxia model employing myoblast cell line H9c2 (Gao et al. 2019) or doxorubicin-induced cardiotoxicity in adult ventricular cardiomyocyte culture (Khan, Varadharaj, Ganesan, et al. 2006). Moreover, an in vivo model of ischaemia/ reperfusion with isolated rat hearts has also been studied . ...
Context
C-Phycocyanin is a protein with anti-scavenger, antioxidant and anti-inflammatory actions against agents that cause cellular damage. The cardioprotective action of C-phycocyanin against acute myocardial infarction (AMI) has not been studied in animal models.
Objective
To investigate C-phycocyanin’s effect on oxidative stress, inflammation and cardiac damage in a model of isoproterenol-induced AMI.
Materials and methods
Wistar rats were divided into four groups: (1) sham + vehicle (0.9% saline solution by oral gavage, OG); (2) sham + C-phycocyanin (50 mg/kg/d, OG); (3) AMI + vehicle, and (4) AMI + C-phycocyanin. AMI was induced by administering isoproterenol (20, 10, 5 and 3 mg/kg each dose per day), and serum cardiac enzymes were quantified. After five days, the animals were euthanized; the heart was dissected to determine oxidative stress, redox environment, inflammation and cardiac damage markers.
Results
We observed that C-phycocyanin reduced AMI-increased cardiac enzymes (CK by about 53%, CKMB by about 60%, AST by about 16% and ALT by about 21%), lipid peroxidation (57%), reactive oxygen species (50%), nitrites (46%), oxidized glutathione (41%), IL1β (3%), INFγ (5%), TNFα 3%), Bcl2 (37%), Bax (43%), COX2 (21%) and caspase 9 (61%). Finally, C-phycocyanin reduced AMI-induced aberrant histological changes related to myonecrosis, interstitial oedema and inflammatory infiltration in the heart muscle.
Conclusions
C-Phycocyanin prevents AMI-induced oxidative stress, inflammation and heart damage. This study is the first report that employed C-phycocyanin in an animal model of AMI and supports the potential use of C-phycocyanin in the management of AMI.
... Mitochondrial fusion helps mitochondria resist oxidative stress-induced damage (42). Studies have shown that mitochondrial fusion and fission impairment may affect mitochondrial function and lead to cardiomyocyte death (43,44). ...
Due to challenges in diagnosing myasthenia gravis (MG), identifying novel diagnostic biomarkers for this disease is essential. Mitochondria are key organelles that regulate multiple physiological functions, such as energy production, cell proliferation and cell death. In the present study, Mfn1/2, Opa1, Drp1, Fis1, AMPK, PGC-1α, NRF-1 and TFAM were compared between patients with MG and healthy subjects to identify potential diagnostic biomarkers for MG. Blood samples were collected from 50 patients with MG and 50 healthy subjects. The participants' demographic information and routine blood test results were recorded. Mitochondrial dynamics were evaluated and levels of Mfn1/2, Opa1, Drp1, Fis1, AMPK, PGC-1α, NRF-1 and TFAM were determined in peripheral blood mononuclear cells using western blotting and reverse transcription-quantitative PCR, respectively. Receiver operating characteristic curve analysis was used to evaluate the diagnostic accuracy of these indicators. The areas under the curve values of Mfn1/2, Opa1, Drp1, Fis1,AMPK, PGC-1α, NRF-1 and TFAM were 0.5408-0.8696. Compared with control subjects, mRNA expression levels of Mfn1/2, Opa1, AMPK, PGC-1α, NRF-1 and TFAM were lower, while those of Drp1 and Fis1 were higher in patients with MG. The protein expression levels of all these molecules were lower in patients with MG than in control subjects. These results suggested that mitochondrial dynamics and biogenesis indicators may be diagnostic biomarkers for MG.
... On the other hand, our results showed that caloric restriction enhanced the relative expression of Nrf1/Tfam/Mgmt and ATP5A1 network in the heart tissue. In this regard, studies have shown that resistance training and a caloric restriction increased mitochondrial fission protein (Opa1 and Mfn1) and PGC-1α expression in the skeletal muscle of rats (Gao et al., 2019). ...
Nrf1/Tfam/MGMT and ATP5A1 might be a pivotal network in cardiovascular disease‐inducing obesity. Therefore, we evaluated eight weeks of exercise, caloric restriction, and spirulina algae consumption on the heart in obese rats. In this study, obese rats were compared with a healthy group. First, we induced obese rats with a 60%‐high‐fat diet. Then, after eight weeks, obese rats were randomly divided into eight groups: obese rats without treatment (HFD), obese rats treated with spirulina algae (HFD‐SA), obese rats conducted exercise (HFD‐EX), obese rats treated with spirulina algae and exercise (HFD‐SA+EX), obese rats treated with caloric restriction (HFD‐CR), obese rats treated with caloric restriction and exercise (HFD‐CR+EX), obese rats treated with spirulina algae and caloric restriction (HFD‐SA+CR), and obese rats treated with SA+CR+EX (HFD‐SA+CR+EX). Also, the exercise protocol was performed for eight weeks, three sessions per week at an intensity of 80%–110% of maximum running speed. The spirulina algae were consumed by gavage (100 mg/kg/day), and caloric restriction used 60% of the food consumed. We found that SA+CR+EX significantly modified the Nrf1/Tfam/MGMT and ATP5A1 network in cardiovascular disease‐inducing obesity rats (p < .01). Moreover, we predicted SA could be bound to Tfam and MGMT protein targets. Hence, exercise, caloric restriction, and spirulina algae had a synergistic effect on mitochondrial biogenesis in the heart tissue of obese rats (p < .01).
Practical applications
According to artificial intelligence and medical biology servers, we discovered that mitochondrial biogenesis and oxidative stress are dominant phenomena in the cardiovascular system. Nrf1/Tfam/MGMT and ATP5A1, as pivotal regulators of oxidative stress, could play an utmost important role in the cardiovascular disease‐inducing obesity molecular pathway. Furthermore, several studies have indicated that environmental factors such as the western diet and physical inactivity disrupted the mitochondrial dynamic, which led to increased reactive oxygen species (ROS). We predicted the binding power of the Spirulina's small molecules on Tfam and Mgmt proteins based on drug‐discovery technology and pharmacokinetic parameters. Considering oxidative stress and mitochondrial machinery related to the action of some molecular pathways, mitochondria‐related nuclear‐encoded proteins, and ROS, this study evaluated the high‐intensity interval training, caloric restriction, and spirulina consumption on heart mitochondrial biogenesis in obese rats. Our data might provide a novel strategy for the prevention and treatment of cardiovascular disease‐inducing obesity.
... Therefore, further studies are necessary to better understand how signaling via both estrogen and testosterone influence cardiac apoptosis in CVD. Necrosis and pyroptosis are inflammatory cell death pathways regulated via caspase enzyme activity, which is induced when irreversible damage occurs in the tissues (Bergsbaken et al., 2009;Gao et al., 2019;Zhaolin et al., 2019). These pathways, more specifically, are initiated when the MPTP is damaged or uncontrolled in mitochondrial fission, as seen in CVD Amgalan et al., 2020). ...
Cardiovascular disease (CVD) is the leading cause of death in the U.S. and worldwide. Sex-related disparities have been identified in the presentation and incidence rate of CVD. Mitochondrial dysfunction plays a role in both the etiology and pathology of CVD. Recent work has suggested that the sex hormones play a role in regulating mitochondrial dynamics, metabolism, and cross talk with other organelles. Specifically, the female sex hormone, estrogen, has both a direct and an indirect role in regulating mitochondrial biogenesis via PGC-1α, dynamics through Opa1, Mfn1, Mfn2, and Drp1, as well as metabolism and redox signaling through the antioxidant response element. Furthermore, data suggests that testosterone is cardioprotective in males and may regulate mitochondrial biogenesis through PGC-1α and dynamics via Mfn1 and Drp1. These cell-signaling hubs are essential in maintaining mitochondrial integrity and cell viability, ultimately impacting CVD survival. PGC-1α also plays a crucial role in inter-organellar cross talk between the mitochondria and other organelles such as the peroxisome. This inter-organellar signaling is an avenue for ameliorating rampant ROS produced by dysregulated mitochondria and for regulating intrinsic apoptosis by modulating intracellular Ca²⁺ levels through interactions with the endoplasmic reticulum. There is a need for future research on the regulatory role of the sex hormones, particularly testosterone, and their cardioprotective effects. This review hopes to highlight the regulatory role of sex hormones on mitochondrial signaling and their function in the underlying disparities between men and women in CVD.
