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Resveratrol reduces DRP1‐mediated mitochondrial dysfunction via the SIRT1‐PGC1α signaling pathway in manganese‐induced nerve damage in mice
- 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.
- Subjects :
- Health, Toxicology and Mutagenesis
Management, Monitoring, Policy and Law
Resveratrol
Toxicology
Mice
DNM1L
chemistry.chemical_compound
Sirtuin 1
Coactivator
medicine
Animals
chemistry.chemical_classification
Manganese
Reactive oxygen species
biology
Neurotoxicity
General Medicine
medicine.disease
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Mitochondria
Cell biology
Mice, Inbred C57BL
chemistry
biology.protein
Signal transduction
Signal Transduction
Deacetylase activity
Subjects
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