Sirtuin 3 attenuates neuroinflammation-induced apoptosis in BV-2 microglia.
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.
['Zhou|Dingzhou|D|', 'Jiang|Yugang|Y|']
D000818:Animals D017209:Apoptosis D002470:Cell Survival D015536:Down-Regulation D005786:Gene Expression Regulation D007249:Inflammation D008070:Lipopolysaccharides D048670:MAP Kinase Kinase 4 D051379:Mice D017628:Microglia D017346:Protein Serine-Threonine Kinases D056566:Sirtuin 3
apoptosis microglial BV-2 cells Sirt3 neuroinflammation Mst1-JNK pathway