SIRT1 Protects Dopaminergic Neurons in Parkinson’s Disease Models via PGC-1α-Mediated Mitochondrial Biogenesis

被引:0
作者
Yu Chen
Yuhui Jiang
Yinuo Yang
Xinzhong Huang
Cheng Sun
机构
[1] Affiliated Hospital of Nantong University,Department of Emergency Medicine
[2] Nantong University,Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products
[3] Affiliated Hospital of Nantong University,Department of Nephrology
[4] Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases,undefined
[5] Institute of Translational Medicine in Cardiothoracic Diseases,undefined
[6] Affiliated Hospital of Nantong University,undefined
来源
Neurotoxicity Research | 2021年 / 39卷
关键词
SIRT1; Dopaminergic neurons; PGC-1α; Mitochondrial biogenesis; Parkinson’s disease;
D O I
暂无
中图分类号
学科分类号
摘要
SIRT1 is a deacetylase with multiple physiological functions by targeting histones and non-histone proteins. It has been shown that SIRT1 activation is involved in neuroprotection in Parkinson’s disease (PD) models. In the present study, we provided direct evidences showing the neuroprotective roles of SIRT1 in dopaminergic neurons. Our data showed that increased expression of SIRT1 plays beneficial roles against MPP+ insults in SH-SY5Y cells and primary dopaminergic neurons, including increased cell viability, reduced LDH release, improved the mitochondrial membrane potential (MMP), and attenuated cell apoptosis. On the contrary, knockdown of SIRT1 further aggravated cell injuries induced by MPP+. Moreover, mutated SIRT1 without deacetylase activity (SIRT1 H363Y) failed to protect dopaminergic neurons from MPP+ injuries. Mechanistically, SIRT1 improved PGC-1α expression and mitochondrial biogenesis. Knockdown of PGC-1α almost completely abolished the neuroprotective roles of SIRT1 in SH-SY5Y cells. Collectively, our data indicate that SIRT1 has neuroprotective roles in dopaminergic neurons, which is dependent upon PGC-1α-mediated mitochondrial biogenesis. These findings suggest that SIRT1 may hold great therapeutic potentials for treating dopaminergic neuron loss associated disorders such as PD.
引用
收藏
页码:1393 / 1404
页数:11
相关论文
共 255 条
[31]  
Zhong G(2017)Sirt3 protects dopaminergic neurons from mitochondrial oxidative stress Hum Mol Genet 26 1915-2262
[32]  
Ciron C(2006)Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators Cell 127 397-1032
[33]  
Zheng L(2014)PCAF improves glucose homeostasis by suppressing the gluconeogenic activity of PGC-1alpha Cell Rep 9 2250-286
[34]  
Bobela W(2010)Distribution analysis of deacetylase SIRT1 in rodent and human nervous systems Anat Rec (hoboken) 293 1024-394
[35]  
Knott GW(2018)SIRT3 protects rotenone-induced injury in SH-SY5Y cells by promoting autophagy through the LKB1-AMPK-mTOR pathway Aging Dis 9 273-41401
[36]  
Leone TC(2019)Effects of mitochondrial dysfunction via AMPK/PGC-1 alpha signal pathway on pathogenic mechanism of diabetic peripheral neuropathy and the protective effects of chinese medicine Chin J Integr Med 25 386-1841
[37]  
Kelly DP(2010)Roles of SIRT1 in the acute and restorative phases following induction of inflammation J Biol Chem 285 41391-undefined
[38]  
Schneider BL(2020)Mir-141-3p regulates apoptosis and mitochondrial membrane potential via targeting Sirtuin1 in a 1-methyl-4-phenylpyridinium in vitro model of Parkinson’s disease Biomed Res Int 2020 7239895-undefined
[39]  
Dorsey ER(2021)Reduced serum SIRT1 levels in patients with Parkinson’s disease: a cross-sectional study in China Neurol Sci 42 1835-undefined
[40]  
Bloem BR(undefined)undefined undefined undefined undefined-undefined