Back to Search Start Over

Resveratrol reduces DRP1‐mediated mitochondrial dysfunction via the SIRT1‐PGC1α signaling pathway in manganese‐induced nerve damage in mice

Authors :
Bin Xu
Lin Cong
Yu Deng
Meng-Yu Lei
Wei Liu
Kuan Liu
Jing Li
Zhuo-Fan Liu
Zhi-Qi Liu
Zhuo Ma
Source :
Environmental Toxicology. 37:282-298
Publication Year :
2021
Publisher :
Wiley, 2021.

Abstract

Excessive manganese (Mn) exposure can cause nerve damage and mitochondrial dysfunction, which may involve defects in mitochondrial dynamics. Resveratrol (RSV) exerts a wide range of beneficial effects via activation of sirtuin 1 (SIRT1) and thus may positively impact Mn-induced mitochondrial damage through the regulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) by SIRT1. In this study, we investigated the molecular mechanisms by which RSV alleviates the nerve injury and mitochondrial fragmentation caused by Mn in C57 BL/6 mice. Our results demonstrated that RSV activated the deacetylase activity of SIRT1 and protected against the surge of mitochondrial reactive oxygen species, the loss of mitochondrial membrane potential, and the attenuation of ATP caused by Mn. RSV, therefore, inhibits mitochondrial fragmentation and safeguards neural cells. Increased deacetylase activity led to a reduction in the acetylation of PGC-1α, which directly regulates DRP1 expression by binding to the DRP1 promoter. The resultant attenuation of DRP1-mediated mitochondrial fragmentation in RSV-pretreated mice was abolished by the addition of the SIRT1 inhibitor EX527. Taken together, these findings indicate that RSV alleviates Mn-induced mitochondrial dysfunction mediated by DRP1 by modulating the SIRT1/PGC-1α signaling pathway.

Details

ISSN :
15227278 and 15204081
Volume :
37
Database :
OpenAIRE
Journal :
Environmental Toxicology
Accession number :
edsair.doi.dedup.....3dfe544cea9dcbe3b589843dfa396ed5
Full Text :
https://doi.org/10.1002/tox.23397