Pharmacological activation of CB2 receptor protects against ethanol-induced myocardial injury related to RIP1/RIP3/MLKL-mediated necroptosis.

Molecular and Cellular Biochemistry
Xiaochen LiuYan Jiang

Abstract

Chronic ethanol abuse can lead to harmful consequences for the heart, resulting in systolic dysfunction, variability in the heart rate, arrhythmia, and cardiac remodelling. However, the precise molecular mechanism responsible for ethanol-induced cardiomyopathy is poorly understood. In this regard, the present study aimed to describe the RIP1/RIP3/MLKL-mediated necroptotic cell death that may be involved in ethanol-induced cardiomyopathy and characterize CBR-mediated effects on the signalling pathway and myocardial injury. We performed an ethanol vapour administration experiment to analyse the effects of ethanol on cardiac structure and function in male C57BL/6J mice. Ethanol induced a significant decline in the cardiac structure and function, as evidenced by a decline in ejection fraction and fractional shortening, and an increase in serum Creatine Kinase levels, myocardial collagen content, and inflammatory reaction. Furthermore, ethanol also upregulated the expression levels of necroptosis-related markers such as p-RIP1, p-RIP3, and p-MLKL in the myocardium. Nec-1 treatment exerted significant cardioprotective effects by salvaging the heart tissue, improving the cardiac function, and mitigating inflammation and necroptosis. I...Continue Reading

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Citations

Jan 1, 2021·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Lin YeYan Jiang
Feb 3, 2021·Autophagy·Soudeh Ghafouri-FardMohammad Taheri
Jul 3, 2021·International Journal of Molecular Sciences·Xinru TangLiliang Li

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Methods Mentioned

BETA
RIP
PCR

Software Mentioned

SPSS
ImageJ

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