Research Paper Volume 11, Issue 20 pp 9075—9089
Sirtuin 3 attenuates neuroinflammation-induced apoptosis in BV-2 microglia
- 1 Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
received: August 9, 2019 ; accepted: October 12, 2019 ; published: October 20, 2019 ;https://doi.org/10.18632/aging.102375
How to Cite
Copyright © 2019 Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
In this study, we explored the upstream regulatory mechanisms underlying inflammation-induced mitochondrial dysfunction in microglial BV-2 cells. Our results demonstrate that Sirtuin 3 (Sirt3) expression was downregulated in response to LPS-induced neuroinflammation. In addition, overexpression of Sirt3 attenuated LPS-induced BV-2 cell death. Functional studies illustrated that Sirt3 overexpression promoted normal mitochondrial function and inhibited mitochondria-dependent apoptosis in LPS-treated BV-2 cells. At the molecular level, suppressor of ras val-2 (SRV2) promoted LPS-mediated mitochondrial damage by inducing mitochondrial fission. Sirt3 overexpression, which suppressed the transcription of SRV2 and thus suppressed mitochondrial fission, played an anti-apoptotic role in LPS-treated BV-2 cells. Furthermore, Sirt3 inhibited SRV2 expression via the Mst1-JNK pathway, and re-activation of this pathway abolished the protective effects of Sirt3 on mitochondrial damage and apoptosis. Taken together, our results indicate that Sirt3-induced, Mst1-JNK-SRV2 signaling pathway-dependent inhibition of mitochondrial fission protected against neuroinflammation-mediated cell damage in BV-2 microglia. Sirt3 might therefore be an effective treatment for neuroinflammation.