Melatonin Postconditioning Ameliorates Anoxia/Reoxygenation Injury by Regulating Mitophagy and Mitochondrial Dynamics in a SIRT3-Dependent Manner

Eur J Pharmacol. 2021 May 7:174157. doi: 10.1016/j.ejphar.2021.174157. Online ahead of print.ABSTRACTIschaemia/reperfusion (I/R) injury is accompanied by excessive mitochondrial autophagy (mitophagy) and an imbalance in mitochondrial dynamics. Melatonin has been reported to alleviate I/R injury by regulating mitophagy and mitochondrial dynamics. However, the underlying mechanism associated with this activity is not fully understood. The goal of the present study was to investigate whether and how melatonin administration at the beginning of reoxygenation exerts protective effects by regulating mitophagy and mitochondrial dynamics. H9c2 cells were transfected with sirtuin 3 (SIRT3)-targeting siRNA and then subjected to anoxia/reoxygenation (A/R) injury, with melatonin (150 μM) administered at the onset of reoxygenation. Biomarkers related to cellular apoptosis, oxidative stress, mitochondrial function, mitophagy and mitochondrial dynamics were assessed, and the expression and activity of SIRT3 was also measured. Mitochondrial fission and mitophagy were activated after A/R injury and were accompanied by cellular apoptosis, oxidative stress, and mitochondrial dysfunction. However, melatonin postconditioning inhibited excessive mitochondrial fission and mitophagy, promoted mitochondrial fusion, restored mitochondrial function and reduced cellular apoptosis, and the mitophagy inhibitor 3-methyladenine (3-MA) also attenuated A/R-induced apoptosis. Moreover, the A/R-induced decreas...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research