title: Resveratrol inhibits β-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway.
abstract: Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid peptide (Aβ) and loss of neurons. Recently, a growing body of evidences have indicated that as a herbal compound naturally derived from grapes, resveratrol modulates the pathophysiology of AD, however, with a largely unclear mechanism. Therefore, we aimed to investigate the protection of resveratrol against the neurotoxicity of β-amyloid peptide 25-35 (Aβ(25-35)) and further explore its underlying mechanism in the present study. PC12 cells were injuried by Aβ(25-35), and resveratrol at different concentrations was added into the culture medium. We observed that resveratrol increased cell viability through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) colorimetric assays. Flow cytometry indicated the reduction of cell apoptosis by resveratrol. Moreover, resveratrol also stabilized the intercellular Ca(2+) homeostasis and attenuated Aβ(25-35) neurotoxicity. Additionally, Aβ(25-35)-suppressed silent information regulator 1 (SIRT1) activity was significantly reversed by resveratrol, resulting in the downregulation of Rho-associated kinase 1 (ROCK1). Our results clearly revealed that resveratrol significantly protected PC12 cells and inhibited the β-amyloid-induced cell apoptosis through the upregulation of SIRT1. Moreover, as a downstream signal molecule, ROCK1 was negatively regulated by SIRT1. Taken together, our study demonstrated that SIRT1-ROCK1 pathway played a critical role in the pathomechanism of AD.
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology and Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, P R China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Feng
authors.forename: Nan
authors.initials: N
authors.lastname: Liang
authors.forename: Dexiao
authors.initials: D
authors.lastname: Zhu
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.forename: Haiman
authors.initials: H
authors.lastname: Dong
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Yue
authors.forename: Haili
authors.initials: H
authors.lastname: Liu
authors.forename: Lihua
authors.initials: L
authors.lastname: Bao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Hao
authors.forename: Yingmao
authors.initials: Y
authors.lastname: Gao
authors.forename: Xuejie
authors.initials: X
authors.lastname: Yu
authors.forename: Jinhao
authors.initials: J
authors.lastname: Sun
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006706:Homeostasis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D000077185:Resveratrol; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; D013267:Stilbenes; D013778:Tetrazolium Salts; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); D007770:L-Lactate Dehydrogenase; C578418:ROCK1 protein, rat; D054460:rho-Associated Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C022616:thiazolyl blue; D000077185:Resveratrol; D002118:Calcium
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