High-dose alcohol induces reactive oxygen species-mediated apoptosis via PKC-β/p66Shc in mouse primary cardiomyocytes

Wang, Yuehong; Jinjun, Zhao; Yang, Wei; Bi, Yang; Chi, Jing; Tian, Juanjuan; Liu, Weimin

doi:10.1016/j.bbrc.2014.12.012

Cited by 40 publications

(55 citation statements)

References 26 publications

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“…77,79 Myocyte apoptosis is the main mechanism of alcohol-induced myocyte loss, and DNA fragmentation is evident in 1-2% of fibres, as determined by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays. 45,81 Ethanol also disturbs cardiac repair mechanisms, increasing the activity of myostatin 82 and decreasing IGF-1 myocardial expression, leading to inhibition of myocyte proliferation. 83 In this situation, alcohol consumption impairs cardiac adaptation and repair mechanisms.…”

Section: Ventricular Function Depressionmentioning

confidence: 99%

Cardiovascular risks and benefits of moderate and heavy alcohol consumption

2015

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The heart and vascular system are susceptible to the harmful effects of alcohol. Alcohol is an active toxin that undergoes widespread diffusion throughout the body, causing multiple synchronous and synergistic effects. Alcohol consumption decreases myocardial contractility and induces arrhythmias and dilated cardiomyopathy, resulting in progressive cardiovascular dysfunction and structural damage. Alcohol, whether at binge doses or a high cumulative lifetime consumption-both of which should be discouraged-is clearly deleterious for the cardiovascular system, increasing the incidence of total and cardiovascular mortality, coronary and peripheral artery disease, heart failure, stroke, hypertension, dyslipidaemia, and diabetes mellitus. However, epidemiological, case-control studies and meta-analyses have shown a U-type bimodal relationship so that low-to-moderate alcohol consumption (particularly of wine or beer) is associated with a decrease in cardiovascular events and mortality, compared with abstention. Potential confounding influences-alcohol-dose quantification, tobacco use, diet, exercise, lifestyle, cancer risk, accidents, and dependence-can affect the results of studies of both low-dose and high-dose alcohol consumption. Mendelian methodological approaches have led to doubts regarding the beneficial cardiovascular effects of alcohol, and the overall balance of beneficial and detrimental effects should be considered when making individual and population-wide recommendations, as reductions in alcohol consumption should provide overall health benefits.

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Section: Ventricular Function Depressionmentioning

confidence: 99%

Cardiovascular risks and benefits of moderate and heavy alcohol consumption

2015

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“…Treatment with PKC inhibitor chelerythrine or BIM-1 abolished fibroblast growth factor-2 (FGF-2) mediated protection against DOX-induced apoptosis, suggesting that PKC activation is an important prosurvival mechanism downstream of FGF-2 [209]. Interestingly, treatment with Ly333531, a specific PKC β inhibitor, attenuated mitochondrial depolarization and apoptosis in response to alcohol and advanced glycation end product, indicating a proapoptotic role of PKC β [210, 211]. …”

Section: Pkcmentioning

confidence: 99%

Signaling Pathways in Cardiac Myocyte Apoptosis

Xia

Liu

Cheng

2016

BioMed Research International

133

132

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Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation.

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“…Adapter protein p66Shc is a well-known mediator of oxidative stress [10], and involved in the injury of cardiomyocytes [40], hepatocytes [22] and renal tubular epithelial cells [32] under pathophysiological conditions. Oxidative stress can induce the phosphorylation of p66Shc at its Ser36 residue, which facilitates binding of p66Shc to cytochrome c within mitochondria [11].…”

Section: Introductionmentioning

confidence: 99%