Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion currently the standard intervention. However, may lead to further myocardial damage, known as ischemia/reperfusion injury (MI/RI). Oxidative stress one of most important pathological mechanisms in injury, causes apoptosis, autophagy, inflammation, some other damage cardiomyocytes through multiple pathways, thus causing irreversible cardiomyocyte cardiac dysfunction. This article reviews oxidative involved interventions different pathways targets, so form systematic treatments stress-induced make up lack monotherapy.

Language: Английский

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Melatonin attenuates diabetic cardiomyopathy and reduces myocardial vulnerability to ischemia‐reperfusion injury by improving mitochondrial quality control: Role of SIRT6

Journal of Pineal Research, Journal Year: 2020, Volume and Issue: 70(1)

Published: Oct. 5, 2020

Abstract Targeting mitochondrial quality control with melatonin has been found promising for attenuating diabetic cardiomyopathy (DCM), although the underlying mechanisms remain largely undefined. Activation of SIRT6 and membrane receptors exerts cardioprotective effects while little is known about their roles during DCM. Using high‐fat diet‐streptozotocin‐induced rat model, we that prolonged diabetes significantly decreased nocturnal circulatory heart levels, reduced expressions cardiac receptors, myocardial AMPK‐PGC‐1α‐AKT signaling. 16 weeks treatment inhibited progression DCM following ischemia‐reperfusion (MI/R) injury by reducing fission, enhancing biogenesis mitophagy via re‐activating After induction diabetes, adeno‐associated virus carrying SIRT6‐specific small hairpin RNA or luzindole was delivered to animals. We showed knockdown antagonizing abolished protective against dysfunction as evidenced aggravated fission mitophagy. Additionally, shRNA melatonin‐induced activation well its actions. Collectively, demonstrated long‐term attenuated vulnerability MI/R through preserving control. Melatonin receptor‐mediated SIRT6‐AMPK‐PGC‐1α‐AKT axis played a key role in this process. may be strategy patients.

Language: Английский

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ALDH2 contributes to melatonin-induced protection against APP/PS1 mutation-prompted cardiac anomalies through cGAS-STING-TBK1-mediated regulation of mitophagy

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: July 23, 2020

Abstract Ample clinical evidence suggests a high incidence of cardiovascular events in Alzheimer’s disease (AD), although neither precise etiology nor effective treatment is available. This study was designed to evaluate cardiac function AD patients and APP/PS1 mutant mice, along with circulating levels melatonin, mitochondrial aldehyde dehydrogenase (ALDH2) autophagy. mice displayed cognitive myocardial deficits, low ALDH2 activity, autophagy, ultrastructural, geometric (cardiac atrophy interstitial fibrosis) functional (reduced fractional shortening cardiomyocyte contraction) anomalies, injury, cytosolic mtDNA buildup, apoptosis, suppressed autophagy mitophagy. mutation downregulated cyclic GMP-AMP synthase (cGAS) stimulator interferon genes (STING) TBK1 phosphorylation, while promoting Aβ accumulation. Treatment melatonin overtly ameliorated unfavorable APP/PS1-induced changes geometry function, integrity, accumulation (using both immunocytochemistry qPCR), mitophagy, cGAS-STING-TBK1 signaling, these benefits were absent APP/PS1/ALDH2 −/− mice. In vitro indicated that attenuated suppression mitophagy the effect negated by nonselective receptor blocker luzindole, inhibitors or RNA interference cGAS, STING, TBK1, Our data collectively established correlation among dysfunction, patients, compelling support which rescued myopathic signaling via an ALDH2-dependent mechanism.

Language: Английский

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ROR: Nuclear Receptor for Melatonin or Not?

Molecules, Journal Year: 2021, Volume and Issue: 26(9), P. 2693 - 2693

Published: May 4, 2021

Whether the retinoic acid-related orphan receptor (ROR) is a nuclear of melatonin remains controversial. ROR inextricably linked to in terms its expression, function, and mechanism action. Additionally, studies have illustrated that functions analogous ligands, thereby modulating transcriptional activity ROR. However, supporting these interactions since been withdrawn. Furthermore, recent crystallographic evidence does not support view melatonin. Some other proposed indirectly regulates rather than directly binding This review aims delve into complex relationship with structure, mechanism. Thus, we provide latest views on direct as well indirect regulation by melatonin, dissecting both viewpoints in-depth more comprehensive perspective this issue.

Language: Английский

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Novel Insight into the Role of Endoplasmic Reticulum Stress in the Pathogenesis of Myocardial Ischemia-Reperfusion Injury

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Impaired function of the endoplasmic reticulum (ER) is followed by evolutionarily conserved cell stress responses, which are employed cells, including cardiomyocytes, to maintain and/or restore ER homeostasis. activates unfolded protein response (UPR) degrade and remove abnormal proteins from lumen. Although UPR an intracellular defense mechanism sustain cardiomyocyte viability heart function, excessive activation initiates ER‐dependent apoptosis. Myocardial ischemia/reperfusion (I/R) injury a pathological process occurring during or after revascularization ischemic myocardium. Several molecular mechanisms contribute pathogenesis cardiac I/R injury. Due dual protective/degradative effects on it interest understand basic concepts, regulatory signals, processes involved in following myocardial In this review, therefore, we present recent findings related novel components activation. The complex whether they mitigate exacerbate summarized serve as basis for research into potential therapies cardioprotection through control

Language: Английский

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<p>Melatonin Attenuates Anoxia/Reoxygenation Injury by Inhibiting Excessive Mitophagy Through the MT2/SIRT3/FoxO3a Signaling Pathway in H9c2 Cells</p>

Drug Design Development and Therapy, Journal Year: 2020, Volume and Issue: Volume 14, P. 2047 - 2060

Published: May 1, 2020

Autophagy caused by ischemia/reperfusion (I/R) increases the extent of cardiomyocyte damage. Melatonin (Mel) diminishes cardiac injury through regulating autophagy and mitochondrial dynamics. However, illustrating specific role mitophagy in cardioprotective effects melatonin remains a challenge. The aim our research was to investigate impact underlying mechanisms connection with during anoxia/reoxygenation (A/R) H9c2 cells.H9c2 cells were pretreated or without membrane receptor 2 (MT2) antagonist 4-P-PDOT, MT2 agonist IIK7 sirtuin 3 (SIRT3) inhibitor 3-TYP for 4 hours then subjected A/R injury. Cell viability, cellular apoptosis, necrosis levels oxidative markers assessed. expression SIRT3 forkhead box O3a (FoxO3a), function mitophagy-related proteins also evaluated.A/R provoked enhanced myocytes. In addition, increased correlated decreased stress dysfunction cells. pretreatment notably cell survival apoptosis response after injury, accompanied restored function. inhibition excessive is involved melatonin, as shown molecules Parkin, Beclin1, BCL2-interacting protein 3-like (BNIP3L, best known NIX) light chain II/light I (LC3 II/LC3 I) ratio upregulation p62 expression. Moreover, FoxO3a A/R-injured abrogated but these beneficial attenuated 4-P-PDOT IIK7.These results indicate that protects suppressing activating MT2/SIRT3/FoxO3a pathway. may be useful candidate alleviating myocardial (MI/R) future, might become therapeutic target.

Language: Английский

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Melatonin protects against thoracic aortic aneurysm and dissection through SIRT1‐dependent regulation of oxidative stress and vascular smooth muscle cell loss

Journal of Pineal Research, Journal Year: 2020, Volume and Issue: 69(1)

Published: April 24, 2020

Abstract Melatonin functions as an endogenous protective molecule in multiple vascular diseases, whereas its effects on thoracic aortic aneurysm and dissection (TAAD) underlying mechanisms have not been reported. In this study, TAAD mouse model was successfully induced by β‐aminopropionitrile fumarate (BAPN). We found that melatonin treatment remarkably prevented the deterioration of TAAD, evidenced decreased incidence, ameliorated aneurysmal dilation stiffness, improved morphology, inhibited elastin degradation, macrophage infiltration, matrix metalloproteinase expression. Moreover, blunted oxidative stress damage smooth muscle cell (VSMC) loss. Notably, BAPN a decrease SIRT1 expression activity aorta, reversed it. Further mechanistic study demonstrated blocking signaling partially these beneficial TAAD. Additionally, receptor involved phenomenon. Our is first to report exerts therapeutic against reducing VSMC loss via activation receptor‐dependent manner, thus suggesting novel strategy for

Language: Английский

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Melatonin promotes cardiomyocyte proliferation and heart repair in mice with myocardial infarction via miR-143-3p/Yap/Ctnnd1 signaling pathway

Acta Pharmacologica Sinica, Journal Year: 2020, Volume and Issue: 42(6), P. 921 - 931

Published: Aug. 24, 2020

Language: Английский

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Melatonin ameliorates aortic valve calcification via the regulation of circular RNA CircRIC3/miR‐204‐5p/DPP4 signaling in valvular interstitial cells

Journal of Pineal Research, Journal Year: 2020, Volume and Issue: 69(2)

Published: May 5, 2020

Calcific aortic valve disease (CAVD) is highly prevalent with marked morbidity and mortality rates a lack of pharmaceutical treatment options because its mechanisms are unknown. Melatonin reported to exert atheroprotective effects. However, whether melatonin protects against calcification, whose pathogenesis shares many similarities that atherosclerosis, the underlying molecular remain In this study, we found intragastric administration for 24 weeks markedly ameliorated calcification in high cholesterol diet (HCD)-treated ApoE-/- mice, as evidenced by reduced thickness calcium deposition leaflets, improved echocardiographic parameters (decreased transvalvular peak jet velocity increased area), decreased osteogenic differentiation marker (Runx2, osteocalcin, osterix) expression valves. Consistent these vivo data, also confirmed suppression vitro hVICs. Mechanistically, level CircRIC3, procalcification circular RNA, which functions acting miR-204-5p sponge positively regulate gene dipeptidyl peptidase-4 (DPP4). Furthermore, CircRIC3 overexpression abolished inhibitory effects on hVIC differentiation. Taken together, our results suggest ameliorates via regulation CircRIC3/miR-204-5p/DPP4 signaling hVICs; therefore, medication might be considered novel strategy CAVD treatment.

Language: Английский

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Melatonin-mediated MT2 attenuates colitis induced by dextran sodium sulfate via PI3K/AKT/Nrf2/SIRT1/RORα/NF-κB signaling pathways

International Immunopharmacology, Journal Year: 2021, Volume and Issue: 96, P. 107779 - 107779

Published: May 24, 2021

Language: Английский

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