Resveratrol Inhibits β-Amyloid-Induced Neuronal Apoptosis through Regulation of SIRT1-ROCK1 Signaling Pathway

Xiaowen Feng, Nan Liang, Dexiao Zhu, Qing Gao, Lei Peng, Haiman Dong, Qingwei Yue, Haili Liu, Lihua Bao, Jing Zhang, Jing Hao, Yingmao Gao, Xuejie Yu, Jinhao Sun

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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 (Aβ25-35) and further explore its underlying mechanism in the present study. PC12 cells were injuried by Aβ25-35, 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 Ca2+ homeostasis and attenuated Aβ25-35 neurotoxicity. Additionally, Aβ25-35-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.

Original languageEnglish (US)
Article numbere59888
JournalPloS one
Volume8
Issue number3
DOIs
StatePublished - Mar 28 2013

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Feng, X., Liang, N., Zhu, D., Gao, Q., Peng, L., Dong, H., Yue, Q., Liu, H., Bao, L., Zhang, J., Hao, J., Gao, Y., Yu, X., & Sun, J. (2013). Resveratrol Inhibits β-Amyloid-Induced Neuronal Apoptosis through Regulation of SIRT1-ROCK1 Signaling Pathway. PloS one, 8(3), [e59888]. https://doi.org/10.1371/journal.pone.0059888