Increased expression of DRAM1 confers myocardial protection against ischemia via restoring autophagy flux

Journal of Molecular and Cellular Cardiology
Xiaoqian WuJiandong Luo

Abstract

DRAM1 (Damage-regulated autophagy modulator 1) was reported as one of the most important lysosome membrane protein that mediates the interaction between autophagosome and lysosome. Our aim was to investigate whether DRAM1 contributes to cardiac remodeling after acute myocardial infarction (AMI) and the underlying mechanisms. Adenovirus harboring DRAM1 was injected in the peri-infarct zone in a rat model of AMI experimentally produced by permanent ligation of left anterior descending (LAD) coronary artery. Increased DRAM1 expression protected the cardiomyocytes from ischemia stress-induced autophagy flux obstacle and improved cardiac prognosis after AMI. DRAM1 overexpression attenuated the accumulation of autophagy substrate protein, LC3IIand p62/SQSTM1 obviously both in vivo and in vitro. An adenovirus harboring mRFP-GFP-LC3 showed that DRAM1 overexpression restored the autophagic flux by enhancing autophagosome conversion to autophagolysosome. Although Atg12 mRNA was up-regulated with DRAM1 overexpression the free Atg12 protein was decreased accompanied by increased Atg12-Atg5 conjugate both in vitro and in vivo. Of interest, immunoprecipitation assay showed that DRAM1 interacted with Atg7, but without direct interaction with ...Continue Reading

Citations

Sep 25, 2020·Medicinal Research Reviews·Xiaoqian WuJiandong Luo
Dec 15, 2020·European Journal of Pharmacology·Milad AshrafizadehMasoud Najafi
Nov 2, 2021·Experimental and Therapeutic Medicine·Yuanyang LiLiping Wei

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