Melatonin elicits protective effects on OGD/R‑insulted H9c2 cells by activating PGC‑1α/Nrf2 signaling

Zhi,Weiwei; Li,Kai; Wang,Hongbing; Lei,Ming; Guo,Yingqiang

doi:10.3892/ijmm.2020.4514

Melatonin elicits protective effects on OGD/R‑insulted H9c2 cells by activating PGC‑1α/Nrf2 signaling

Authors:
- Weiwei Zhi
- Kai Li
- Hongbing Wang
- Ming Lei
- Yingqiang Guo
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Affiliations: Department of Cardiology, Xi'an No. 3 Hospital, Xi'an, Shaanxi 710018, P.R. China, Department of Cardiology, Xi'an No. 3 Hospital, Xi'an, Shaanxi 710018, P.R. China, Department of Cardiology, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712000, P.R. China
Published online on: February 25, 2020 https://doi.org/10.3892/ijmm.2020.4514
Pages: 1294-1304
Copyright: © Zhi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Melatonin (Mel) elicits beneficial effects on myocardial ischemia/reperfusion injury. However, the underlying mechanism of Mel against oxygen‑glucose deprivation/reperfusion (OGD/R)‑induced H9c2 cardiomyocyte damage remains largely unknown. The aim of the present study was to investigate the biological roles and the potential mechanisms of Mel in OGD/R‑exposed H9c2 cardiomyocytes. The results of the present study demonstrated that Mel significantly elevated the viability and reduced the activity of lactate dehydrogenase and creatine kinase myocardial band in a dose‑ and time‑dependent manner in OGD/R‑insulted H9c2 cells. In addition, Mel suppressed OGD/R‑induced oxidative stress in H9c2 cells, as demonstrated by the decreased reactive oxygen species and malondialdehyde levels, as well as the increased activities of superoxide dismutase, catalase and glutathione peroxidase. Mel exerted an antioxidant effect by activating the peroxisome proliferator‑activated receptor gamma coactivator‑1α (PGC‑1α)/nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling. Mel reduced the expression of OGD/R‑enhanced pro‑inflammatory tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6, IL‑1β, IL‑8 and monocyte chemotactic protein‑1. Mel also abolished the OGD/R‑induced increase in H9c2 apoptosis, as evidenced by mitochondrial membrane potential restoration and caspase‑3 and caspase‑9 inactivation, as well as the upregulation of Bcl‑2 and downregulation of cleaved caspase‑3 and Bax. The Mel‑induced antiapoptotic effects were dependent on PGC‑1α/TNF‑α signaling. Overall, the results of the present study demonstrated that Mel alleviated OGD/R‑induced H9c2 cell injury via the inhibition of oxidative stress and inflammation by regulating the PGC‑1α/Nrf2 and PGC‑1α/TNF‑α signaling pathways, suggesting a promising role for Mel in the treatment of ischemic heart disease.

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