SIRT3 and RORα Are Two Prospective Targets Against Mitophagy During Simulated Ischemia/reperfusion Injury in H9c2 Cells

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 May 24

PMID 38784556

Authors

Jinjing Wu

Yanli Yang

Duomao Lin

Zhaoqi Wang

Jun Ma

Affiliations

Soon will be listed here.

Abstract

Autophagy during myocardial ischemia/reperfusion (MI/R) exacerbates cardiomyocyte injury. Melatonin (Mel) alleviates myocardial damage by regulating mitochondrial function and mitophagy, but the role of mitophagy in melatonin-induced cardioprotection remains unclear. This study aimed to explore the roles of sirtuin3 (SIRT3) and retinoid-related orphan nuclear receptor-α (RORα) in mitophagy during simulated ischemia reperfusion (SIR) in H9c2 cells. Our data showed that mitophagy was excessively activated after SIR injury, which was consistent with reduced cell survival, enhanced oxidative responses and mitochondrial dysfunction in H9c2 myocytes. Melatonin greatly enhanced cell viability, reduced oxidative stress and improved mitochondrial function. The effects of melatonin protection were involved in excessive mitophagy inhibition, as demonstrated by the reduced levels of mitophagy-linked proteins, including Parkin, Beclin1, NIX and BNIP3, and the LC3 II/LC3 I ratio and elevations in p62. Additionally, the decreases in SIRT3 and RORα in H9c2 myocytes after SIR were reversed by melatonin, and the above effects of melatonin were eliminated by small interfering RNA (siRNA)-mediated knockdown of SIRT3 and RORα. In brief, SIRT3 and RORα are two prospective targets in the cardioprotection of melatonin against mitophagy during SIR in H9c2 myocytes.

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