神经炎症
下调和上调
细胞生物学
SIRT3
活力测定
细胞凋亡
信号转导
肿瘤坏死因子α
生物
化学
癌症研究
炎症
免疫学
生物化学
锡尔图因
乙酰化
基因
作者
Yang Yang,Zhongying Gong,Zhiyun Wang
标识
DOI:10.1080/10799893.2019.1705339
摘要
Objective: Neuroinflammation is linked to a series of neurodegenerative diseases through the unknown mechanisms.Aim: The aim of this study was to investigate the role of Yes-associated protein (Yap) in the regulation of neuroinflammation.Methods: BV-2 neuroglia cells were treated with TNFα in vitro. Then, western blots, qPCR, immunofluorescence, and ELISA were used to verify the influence of Yap in BV-2 cells neuroinflammation response.Results: After exposure to TNFα, viability of BV-2 cells decreased whereas apoptosis index was increased. Of note, Yap expression in BV-2 cells was significantly reduced, when compared to the normal cells. Interestingly, adenovirus-induced Yap overexpression was capable to reverse cell viability and thus reduce apoptotic index in TNFα-treated BV-2 cells. Molecular investigation demonstrated that Yap overexpression was linked to Sirt3 upregulation. Increased Sirt3 reduced endoplasmic reticulum (ER) stress, attenuated mitochondrial damage, and blocked JNK pro-apoptotic pathway. Interestingly, loss of Sirt3 abolished the protective effects induced by Yap overexpression in TNFα-treated BV-2 cells.Conclusions: Altogether, our results demonstrated that neuroinflammation could be caused by Yap downregulation, possible driven through Sirt3 inhibition and JNK activation. However, overexpression of Yap could protect BV-2 cells against TNFα-mediated apoptosis through modulating Sirt3-JNK signaling pathways.
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