Dataset Information

Ferulic Acid Attenuates Hypoxia/Reoxygenation Injury by Suppressing Mitophagy Through the PINK1/Parkin Signaling Pathway in H9c2 Cells.

ABSTRACT: Ferulic acid protects against cardiac injury by scavenging free radicals. However, the role of mitophagy in ferulic acid-induced cardioprotection remains obscure. In the present study, H9c2 cells were exposed to hypoxia/reoxygenation and ferulic acid treatment during hypoxia. We illustrated the impact of ferulic acid on oxidative damage in H9c2 cells. Our results showed that ferulic acid significantly attenuated apoptosis induced by hypoxia/reoxygenation injury and reduced mitochondrial dysfunction, evidenced by a decline in the overproduction of reactive oxygen species and ATP depletion and recovery of the membrane potential. We also found that mitophagy, a selective form of autophagy, was excessively activated in H9c2 cells subjected to hypoxia/reoxygenation. Ferulic acid reduced the binding of mitochondria to lysosomes, down-regulated the PINK1/Parkin pathway, and was accompanied by increased p62 and decreased LC3-II/LC3-I levels. Ferulic acid also antagonistically reduced the activation of mitophagy by rapamycin. These findings suggest that ferulic acid may protect H9c2 cells against ischemia/reperfusion injury by suppressing PINK1/Parkin-dependent mitophagy. Accordingly, our findings may provide a potential target and powerful reference for ferulic acid in clinical prevention and treatment of hypoxia/reoxygenation injury.

SUBMITTER: Luo C

PROVIDER: S-EPMC7052384 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ferulic Acid Attenuates Hypoxia/Reoxygenation Injury by Suppressing Mitophagy Through the PINK1/Parkin Signaling Pathway in H9c2 Cells.

Luo Chenxi C Zhang Yehao Y Guo Hao H Han Xiao X Ren Junguo J Liu Jianxun J

Frontiers in pharmacology 20200225

Ferulic acid protects against cardiac injury by scavenging free radicals. However, the role of mitophagy in ferulic acid-induced cardioprotection remains obscure. In the present study, H9c2 cells were exposed to hypoxia/reoxygenation and ferulic acid treatment during hypoxia. We illustrated the impact of ferulic acid on oxidative damage in H9c2 cells. Our results showed that ferulic acid significantly attenuated apoptosis induced by hypoxia/reoxygenation injury and reduced mitochondrial dysfunct ...[more]

PMID: 32161543

Similar Datasets

Project description:PurposeAutophagy caused by ischemia/reperfusion (I/R) increases the extent of cardiomyocyte damage. Melatonin (Mel) diminishes cardiac injury through regulating autophagy and mitochondrial dynamics. However, illustrating the specific role of mitophagy in the cardioprotective effects of melatonin remains a challenge. The aim of our research was to investigate the impact and underlying mechanisms of melatonin in connection with mitophagy during anoxia/reoxygenation (A/R) injury in H9c2 cells.MethodsH9c2 cells were pretreated with melatonin with or without the melatonin membrane receptor 2 (MT2) antagonist 4-P-PDOT, the MT2 agonist IIK7 and the sirtuin 3 (SIRT3) inhibitor 3-TYP for 4 hours and then subjected to A/R injury. Cell viability, cellular apoptosis, necrosis levels and oxidative markers were assessed. The expression of SIRT3 and forkhead box O3a (FoxO3a), mitochondrial function and the levels of mitophagy-related proteins were also evaluated.ResultsA/R injury provoked enhanced mitophagy in H9c2 myocytes. In addition, increased mitophagy was correlated with decreased cellular viability, increased oxidative stress and mitochondrial dysfunction in H9c2 cells. However, melatonin pretreatment notably increased cell survival and decreased cell apoptosis and oxidative response after A/R injury, accompanied by restored mitochondrial function. The inhibition of excessive mitophagy is involved in the cardioprotective effects of melatonin, as shown by the decreased expression of the mitophagy-related molecules Parkin, Beclin1, and BCL2-interacting protein 3-like (BNIP3L, best known as NIX) and decreased light chain 3 II/light chain 3 I (LC3 II/LC3 I) ratio and upregulation of p62 expression. Moreover, the decreased expression of SIRT3 and FoxO3a in A/R-injured H9c2 cells was abrogated by melatonin, but these beneficial effects were attenuated by the MT2 antagonist 4-P-PDOT or the SIRT3 inhibitor 3-TYP and enhanced by the MT2 agonist IIK7.ConclusionThese results indicate that melatonin protects H9c2 cells during A/R injury through suppressing excessive mitophagy by activating the MT2/SIRT3/FoxO3a pathway. Melatonin may be a useful candidate for alleviating myocardial ischemia/reperfusion (MI/R) injury in the future, and the MT2 receptor might become a therapeutic target.

Dataset Information

Ferulic Acid Attenuates Hypoxia/Reoxygenation Injury by Suppressing Mitophagy Through the PINK1/Parkin Signaling Pathway in H9c2 Cells.

Publications

Ferulic Acid Attenuates Hypoxia/Reoxygenation Injury by Suppressing Mitophagy Through the PINK1/Parkin Signaling Pathway in H9c2 Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets