Resveratrol inhibits β-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway

• Published in: PloS one Vol. 8; no. 3; p. e59888
• Main Authors: Feng, Xiaowen, Liang, Nan, Zhu, Dexiao, Gao, Qing, Peng, Lei, Dong, Haiman, Yue, Qingwei, Liu, Haili, Bao, Lihua, Zhang, Jing, Hao, Jing, Gao, Yingmao, Yu, Xuejie, Sun, Jinhao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.03.2013; Public Library of Science (PLoS)
• Subjects: Aging; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Antioxidants - pharmacology; Apoptosis; Biology; Calcium - metabolism; Calcium homeostasis; Calcium ions; Cell culture; Cell Survival; Colorimetry; Cytometry; Cytotoxicity; Disease; Education; Embryology; Flow Cytometry; Gene Expression Regulation; Grapes; Histology; Homeostasis; Kinases; L-Lactate dehydrogenase; L-Lactate Dehydrogenase - metabolism; Laboratories; Lactate dehydrogenase; Lactic acid; Medicine; Neurodegenerative Diseases - metabolism; Neurons - metabolism; Neurotoxicity; PC12 Cells; Peptide Fragments - metabolism; Pheochromocytoma cells; Proteins; Rats; Resveratrol; Rho-associated kinase; rho-Associated Kinases - metabolism; Rodents; Signal Transduction; Signaling; SIRT1 protein; Sirtuin 1 - metabolism; Stilbenes - pharmacology; Tetrazolium Salts; Thiazoles; β-Amyloid; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0059888

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.