Open AccessEGCG protects cardiomyocytes against hypoxia-reperfusion injury via inhibiting OMA1 activation
Author(s) -
Jinliang Nan,
Cunjin Nan,
Jian Ye,
Qian Lü,
Yun Geng,
Dawei Xing,
Muhammad Saif Ur Rahman,
Ming-Yuan Huang
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.220871
Subject(s) - biology , hypoxia (environmental) , microbiology and biotechnology , pharmacology , reperfusion injury , medicine , ischemia , oxygen , chemistry , organic chemistry
Mitochondria are important for energy production and cardiomyocytes homeostasis. OMA1, a metalloendopeptidase, initiates the proteolytic process of pro-fusion protein, OPA1, to deteriorate mitochondrial structure and function. In this study, mouse embryonic fibroblasts (MEFs) and neonatal mouse cardiomyocytes (NMCMs) subjected to hypoxia-reperfusion (H/R) and/or H2O2 were used to mimic oxidative stress in the heart following ischemia-reperfusion (I/R). In vitro experiments demonstrated that H/R insult and H2O2 stimulation induced self-cleavage of OMA1 and subsequent conversion of OPA1 from long form to short form, leading to mitochondrial fragmentation, cytochrome c release, and apoptosis. By using Molecular Operating Environment (MOE) to simulate the binding interaction of 2295 phytochemicals against OMA1, epigallocatechin gallate (EGCG) and betanin were selected as candidates of OMA1 inhibitor. We found that EGCG directly interacted with OMA1 and potently inhibited self-cleavage of OMA1, leading to attenuated OPA1 cleavage. This study suggests that OMA1 inhibition induced by EGCG can serve as a potential approach to treat cardiac I/R injury.