SIRT1 confers protection against ischemia/reperfusion injury in cardiomyocytes via regulation of uncoupling protein 2 expression

Deng, Min; Wang, Daxin; He, Shenghu; Xu, Rixin; Xie, Yuanyuan

doi:10.3892/mmr.2017.7452

Cited by 23 publications

(10 citation statements)

References 19 publications

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“…Quercetin could directly scavenge free radicals [26], which might lessen oxidative stress. Sirt1 normally confers protection against ischemia/reperfusion damages in cardiomyocytes whereby different mechanisms [27][28][29]. In response to hypoxic stress, sirt1 facilitates autophagy via activating AMPK with attenuating hypoxia-evoked apoptosis [30].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Quercetin supports cell viability and inhibits apoptosis in cardiocytes by down-regulating miR-199a

Guo

Gong

Sun

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Hypoxia-caused cardiocytes insults are closely correlated with ectopic expression of genes, which might be modulated by microRNAs (miRs). Quercetin exhibits a profound protective function against hypoxic damages in cardiomyocytes. Here, we aimed to investigate a possible underpinning. H9c2 cells were pre-administrated using quercetin before hypoxia treatment. The damages were assessed using viability, apoptosis and alteration of proteins associated with apoptosis and adenosine monophosphate-activated protein (AMPK) pathway. Transfection was conducted to enforce overexpression of miR-199a or silence of sirtuin 1 (sirt1) which were confirmed by qRT-PCR. Sirt1 protein was quantified by immunoblotting. A luciferase reporter was exploited to confirm the target relationship between miR-199a and sirt1 3 0-untranslated region (3 0-UTR). We found quercetin mitigated hypoxia-caused viability reduction and apoptosis with restoring apoptosis-associated protein and rescuing phosphorylation of AMPK. Quercetin flattened hypoxia-evoked overexpression of miR-199a. miR-199a abrogated the protective effects of quercetin against hypoxia-elicited damages. Quercetin elevated sirt1 which was repressed by hypoxia, while this effect was slight in miR-199a-overexpressed cells. miR-199a negatively mediated sirt1 expression through directly binding its 3 0-UTR. Further, quercetin facilitated the phosphorylation of AMPK by up-regulating sirt1. Collectively, quercetin participated in repressing miR-199a which negatively modulated sirt1. Mechanically, through activating AMPK, quercetin protected cardiomyocytes cells against hypoxia-caused insults. HIGHLIGHTS Quercetin ameliorates hypoxia-evoked apoptosis and blockage of AMPK phosphorylation; The elevated miR-199a level is eased by quercetin, which might be a protective mechanism; Quercetin restores sirt1 level by repressing miR-199a expression; By mediating miR-199a and sirt1, AMPK phosphorylation is fortified by quercetin.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Quercetin supports cell viability and inhibits apoptosis in cardiocytes by down-regulating miR-199a

Guo

Gong

Sun

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Elevation of UCP2 expression suppresses oxidative stress and reduces both myocardial remodelling and apoptosis in resveratrol‐treated rats with cardiomyopathy (Diao et al, ). A recent study shows that intraperitoneal resveratrol injection protects cardiomyocytes against ischaemia/reperfusion injury through a SIRT1/UCP2‐dependent mechanism (Deng et al, ). Although SIRT1 directly docks to the UCP2 promoter for transcriptional activation (Olmos et al, ), a comprehensive mechanism underlying the interplay between AMPK, UCP2, and SIRT1 is still lacking.…”

Section: Molecular Basis Of Resveratrol Actionmentioning

confidence: 99%

Pharmacological basis and new insights of resveratrol action in the cardiovascular system

Cheng

Luo

Lau

et al. 2019

British J Pharmacology

113

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Resveratrol (trans‐3,4′,5‐trihydroxystilbene) belongs to the family of natural phytoalexins. Resveratrol first came to our attention in 1992, following reports of the cardioprotective effects of red wine. Thereafter, resveratrol was shown to exert antioxidant, anti‐inflammatory, anti‐proliferative, and angio‐regulatory effects against atherosclerosis, ischaemia, and cardiomyopathy. This article critically reviews the current findings on the molecular basis of resveratrol‐mediated cardiovascular benefits, summarizing the broad effects of resveratrol on longevity regulation, energy metabolism, stress resistance, exercise mimetics, circadian clock, and microbiota composition. In addition, this article also provides an update, both preclinically and clinically, on resveratrol‐induced cardiovascular protection and discusses the adverse and inconsistent effects of resveratrol reported in both preclinical and clinical studies. Although resveratrol has been claimed as a master anti‐aging agent against several age‐associated diseases, further detailed mechanistic investigation is still required to thoroughly unravel the therapeutic value of resveratrol against cardiovascular diseases at different stages of disease development. Linked Articles This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc

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“…Moreover, a gene knockdown approach demonstrates that UCP2 is required for augmenting the ischemia tolerance of myocardium ( McLeod et al, 2005 ). The cardioprotective effect of SIRT1 is also mediated by UCP2 in IR injury ( Deng et al, 2017 ). UCP2 is often used recently as a protective marker for oxidative stress and mitochondrial injury in animal models of cardiac injury or ischemic insults ( Castillo et al, 2018 ; Quan et al, 2018 ; Wang et al, 2018 ) ( Table 2 ).…”

Section: Ucp2 and Cardiac Diseasesmentioning

confidence: 99%

Uncoupling Protein 2 in Cardiovascular Health and Disease

Tian

Tse

et al. 2018

Front. Physiol.

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Uncoupling protein 2 (UCP2) belongs to the family of mitochondrial anion carrier proteins. It uncouples oxygen consumption from ATP synthesis. UCP2 is ubiquitously expressed in most cell types to reduce oxidative stress. It is tightly regulated at the transcriptional, translational, and post-translational levels. UCP2 in the cardiovascular system is being increasingly recognized as an important molecule to defend against various stress signals such as oxidative stress in the pathology of vascular dysfunction, atherosclerosis, hypertension, and cardiac injuries. UCP2 protects against cellular dysfunction through reducing mitochondrial oxidative stress and modulation of mitochondrial function. In view of the different functions of UCP2 in various cell types that contribute to whole body homeostasis, cell type-specific modification of UCP2 expression may offer a better approach to help understanding how UCP2 governs mitochondrial function, reactive oxygen species production and transmembrane proton leak and how dysfunction of UCP2 participates in the development of cardiovascular diseases. This review article provided an update on the physiological regulation of UCP2 in the cardiovascular system, and also discussed the involvement of UCP2 deficiency and associated oxidative stress in the pathogenesis of several common cardiovascular diseases. Drugs targeting UCP2 expression and activity might serve another effective strategy to ameliorate cardiovascular dysfunction. However, more detailed mechanistic study will be needed to dissect the role of UCP2, the regulation of UCP2 expression, and the cellular responses to the changes of UCP2 expression in normal and stressed situations at different stages of cardiovascular diseases.

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SIRT1 confers protection against ischemia/reperfusion injury in cardiomyocytes via regulation of uncoupling protein 2 expression

Cited by 23 publications

References 19 publications

RETRACTED ARTICLE: Quercetin supports cell viability and inhibits apoptosis in cardiocytes by down-regulating miR-199a

RETRACTED ARTICLE: Quercetin supports cell viability and inhibits apoptosis in cardiocytes by down-regulating miR-199a

Pharmacological basis and new insights of resveratrol action in the cardiovascular system

Uncoupling Protein 2 in Cardiovascular Health and Disease

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