期刊
MOLECULES
卷 27, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/molecules27175545
关键词
autophagy; MIRI; mitochondrial quality control; resveratrol
资金
- Innovative Research Group Project of the National Natural Science Foundation of China [81470182]
- Minzu University of China [2020MDJC04]
Resveratrol protects against myocardial ischemia/reperfusion injury by activating the Sirt1/Sirt3-FoxO pathway on myocardial mitochondria. It repairs mitochondrial dynamics, autophagic flux, and mitochondrial biosynthesis, leading to improved mitochondrial function and antioxidant enzyme system.
Resveratrol is a natural polyphenol found in various plants. It has been widely studied on cardiovascular disorders. It is known that resveratrol can activate Sirtuin proteins and participate in cellular energy metabolism through a Sirtuin-dependent pathway. Here, we hypothesized that resveratrol may protect against myocardial ischemia/reperfusion injury (MIRI) through the target of Sirt1/Sirt3 on mitochondrial dynamics, cardiac autophagy, bioenergetics and oxidative damage in hypoxia/reoxygenation (H/R)-induced neonatal rat cardiomyocytes. We observed that resveratrol could activate the Sirt1/Sirt3-FoxO pathway on myocardial mitochondria in H/R cardiomyocytes. Subsequently, we found that resveratrol repaired the fission-fusion balance, autophagic flux and mitochondrial biosynthesis compared by H/R group. These changes were followed by increased functional mitochondrial number, mitochondrial bioenergetics and a better mitochondrial antioxidant enzyme system. Meanwhile, these effects were antagonized by co-treatment with Selisistat (Ex527), a Sirtuin inhibitor. Together, our findings uncover the potential contribution of resveratrol in reestablishing a mitochondrial quality control network with Parkin, Mfn2 and PGC-1 alpha as the key nodes.
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