Yes-associated protein reduces neuroinflammation through upregulation of Sirt3 and inhibition of JNK signaling pathway

Abstract

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.

Keywords:

• Yap
• neuroinflammation
• BV-2 cells
• apoptosis
• ER stress

Disclosure statement

No potential conflict of interest was reported by the authors.