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Neurochem Res. 2016 Jul;41(7):1761-73. doi: 10.1007/s11064-016-1892-2. Epub 2016 Apr 6.

SIRT3 Acts as a Neuroprotective Agent in Rotenone-Induced Parkinson Cell Model.

Author information

1
Department of Neurology, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Rd, Xi'an, 710061, China.
2
Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, San Francisco, CA, USA.
3
Department of Neurology, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Rd, Xi'an, 710061, China. quqiumin@medmail.com.cn.

Abstract

SIRT3 is a member of Sirtuins family, which belongs to NAD(+) dependent class III histone deacetylases. Emerging evidence suggests that SIRT3 plays a pivotal role in regulating mitochondrial function. Mitochondrial dysfunction is a main pathogenesis of Parkinson's disease (PD). Here, we have investigated the protective effect of SIRT3 for PD cell model. The rotenone-induced human neuroblastoma SH-SY5Y cells damage was used as PD cell model. The lentiviral vectors were used to over-expression or knockdown SIRT3 expression. The cell viability was analyzed using MTT method. The apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were measured by flow cytometer. Superoxide dismutase (SOD) and glutathione (GSH) were detected by using automated microplate reader. The accumulation of α-synuclein was determined by immunofluorescence staining. SIRT3 knockdown significantly worsen rotenone-induced decline of cell viability (p < 0.01) and enhanced cell apoptosis (p < 0.01), exacerbated the decrease of SOD (p < 0.05) and GSH (p < 0.05), and augmented the accumulation of α-synuclein (p < 0.05). While SIRT3 overexpression dramatically increased cell viability (p < 0.01), and decreased cell apoptosis (p < 0.01), prevented the accumulation of α-synuclein (p < 0.05), suppressed the reducing of SOD (p < 0.05) and GSH (p < 0.01), decreased ROS generation (p < 0.05), and alleviated MMP collapse (p < 0.01) induced by rotenone. SIRT3 has neuroprotective effect in PD cell model and could be developed into a therapeutic agent for PD patients.

KEYWORDS:

Mitochondrial dysfunction; Neuroprotection; Oxidative stress; Parkinson’s disease; SIRT3; α-Synuclein

PMID:
27053302
DOI:
10.1007/s11064-016-1892-2
[Indexed for MEDLINE]

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