MA Eraser ALKBH5 Mitigates the Apoptosis of Cardiomyocytes in Ischemia Reperfusion Injury Through MA/SIRT1 Axis

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2023 May 16

PMID 37193033

Authors

Liangliang Liu

Zhen Liu

Affiliations

Soon will be listed here.

Abstract

Recent studies have shown that the potential regulatory role of N-methyladenine (mA) modification may affect the occurrence and development of various cardiovascular diseases. However, the regulatory mechanism of mA modification on myocardial ischemia reperfusion injury (MIRI) is rarely reported. A mouse model of myocardial ischemia reperfusion (I/R) was established by ligation and perfusion of the left anterior descending coronary artery, and a cellular model of hypoxia/reperfusion (H/R) was conducted in cardiomyocytes (CMs). We found that the protein expression of ALKBH5 in myocardial tissues and cells were decreased, accompanied by increased mA modification level. Overexpression of ALKBH5 significantly inhibited H/R-induced oxidative stress and apoptosis in CMs. Mechanistically, there was an enriched mA motif in the 3'-UTR of SIRT1 genome, and ALKBH5 overexpression promoted the stability of SIRT1 mRNA. Furthermore, results using overexpression or knockdown of SIRT1 confirmed the protective effect of SIRT1 on H/R induced CMs apoptosis. Together, our study reveals a critical role of ALKBH5-medicated mA on CM apoptosis, supplying an important regulating effect of mA methylation in ischemic heart disease.

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