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Resveratrol Attenuates Aβ25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway

Resveratrol Attenuates Aβ25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway

Haoyue Deng, Man-Tian Mi

Neurochem Res. 2016 Sep;41(9):2367-79.

PMID: 27180189

Abstract:

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of β-amyloid peptide (Aβ) and loss of neurons. Resveratrol (RSV) is a natural polyphenol that has been found to be beneficial for AD through attenuation of Aβ-induced toxicity in neurons both in vivo and in vitro. However, the specific underlying mechanisms remain unknown. Recently, autophagy was found to protect neurons from toxicity injuries via degradation of impaired proteins and organelles. Therefore, the aim of this study was to determine the role of autophagy in the anti-neurotoxicity effect of RSV in PC12 cells. We found that RSV pretreatment suppressed β-amyloid protein fragment 25-35 (Aβ25-35)-induced decrease in cell viability. Expression of light chain 3-II, degradation of sequestosome 1, and formation of autophagosomes were also upregulated by RSV. Suppression of autophagy by 3-methyladenine abolished the favorable effects of RSV on Aβ25-35-induced neurotoxicity. Furthermore, RSV promoted the expression of sirtuin 1 (SIRT1), auto-poly-ADP-ribosylation of poly (ADP-ribose) polymerase 1 (PARP1), as well as tyrosyl transfer-RNA (tRNA) synthetase (TyrRS). Nevertheless, RSV-mediated autophagy was markedly abolished with the addition of inhibitors of SIRT1 (EX527), nicotinamide phosphoribosyltransferase (STF-118804), PARP1 (AG-14361), as well as SIRT1 and TyrRS small interfering RNA transfection, indicating that the action of RSV on autophagy induction was dependent on TyrRS, PARP1 and SIRT1. In conclusion, RSV attenuated neurotoxicity caused by Aβ25-35 through inducing autophagy in PC12 cells, and the autophagy was partially mediated via activation of the TyrRS-PARP1-SIRT1 signaling pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP894187612	STF-118804		894187-61-2	Price

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