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Alpha-synuclein knockdown attenuates MPP+ induced mitochondrial dysfunction of SH-SY5Y cells.
Brain Res. 2009 Oct 06; 1292:173-9.BR

Abstract

Alpha-synuclein is one of the main constituents of Lewy bodies and plays an important role in the pathology of Parkinson's disease. Mutation or overexpression of alpha-synuclein causes Parkinson's disease, and downregulation of alpha-synuclein resists MPP(+)-induced cell death, but the mechanism remains elusive. In this study, we attempted to explore the effect of alpha-synuclein knockdown on mitochondrial function in MPP(+)-treated SH-SY5Y cells. We reconstructed the short hairpin RNA expression vector, pGenesil-2, specially targeting alpha-synuclein mRNA, and it was stably transfected into SH-SY5Y cells. Cell viability, nuclear morphology, and mitochondrial membrane potential were then detected, and the expression of alpha-synuclein, cytochrome c, Bcl-2 and Bax were analyzed by Western blotting. The results showed that after exposure to 500 microM MPP(+) for 24 h, about 41.0+/-1.5% control cells showed low mitochondrial membrane potential. However, the percentage was 13.6+/-1.2% in MPP(+) treated alpha-synuclein knockdown cells. MPP(+) induced cytochrome c release significantly, which was about 3.1-fold compared with that of control. However, in alpha-synuclein knockdown cells, the release of cytochrome c was blocked, which was about 1.4-fold compared with that of control. The Bcl-2/Bax ratio of SH-SY5Y cells reduced to 35.5+/-3.8% after MPP(+) treatment, and this ratio was 85.2+/-3.0% in MPP(+) treated alpha-synuclein knockdown cells. These data suggest that knockdown of alpha- synuclein might be an effective means in rescuing MPP(+)-induced mitochondrial dysfunction of SH-SY5Y cells.

Authors+Show Affiliations

Department of Anatomy, Shandong University School of Medicine, 44 Wen-hua Xi Road, Jinan, Shandong Province 250012, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19646423

Citation

Wu, Fengxia, et al. "Alpha-synuclein Knockdown Attenuates MPP+ Induced Mitochondrial Dysfunction of SH-SY5Y Cells." Brain Research, vol. 1292, 2009, pp. 173-9.
Wu F, Poon WS, Lu G, et al. Alpha-synuclein knockdown attenuates MPP+ induced mitochondrial dysfunction of SH-SY5Y cells. Brain Res. 2009;1292:173-9.
Wu, F., Poon, W. S., Lu, G., Wang, A., Meng, H., Feng, L., Li, Z., & Liu, S. (2009). Alpha-synuclein knockdown attenuates MPP+ induced mitochondrial dysfunction of SH-SY5Y cells. Brain Research, 1292, 173-9. https://doi.org/10.1016/j.brainres.2009.07.067
Wu F, et al. Alpha-synuclein Knockdown Attenuates MPP+ Induced Mitochondrial Dysfunction of SH-SY5Y Cells. Brain Res. 2009 Oct 6;1292:173-9. PubMed PMID: 19646423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha-synuclein knockdown attenuates MPP+ induced mitochondrial dysfunction of SH-SY5Y cells. AU - Wu,Fengxia, AU - Poon,Wai Sang, AU - Lu,Gang, AU - Wang,Ancong, AU - Meng,Haiwei, AU - Feng,Lei, AU - Li,Zhenping, AU - Liu,Shuwei, Y1 - 2009/07/29/ PY - 2009/04/03/received PY - 2009/07/15/revised PY - 2009/07/16/accepted PY - 2009/8/4/entrez PY - 2009/8/4/pubmed PY - 2009/11/7/medline SP - 173 EP - 9 JF - Brain research JO - Brain Res VL - 1292 N2 - Alpha-synuclein is one of the main constituents of Lewy bodies and plays an important role in the pathology of Parkinson's disease. Mutation or overexpression of alpha-synuclein causes Parkinson's disease, and downregulation of alpha-synuclein resists MPP(+)-induced cell death, but the mechanism remains elusive. In this study, we attempted to explore the effect of alpha-synuclein knockdown on mitochondrial function in MPP(+)-treated SH-SY5Y cells. We reconstructed the short hairpin RNA expression vector, pGenesil-2, specially targeting alpha-synuclein mRNA, and it was stably transfected into SH-SY5Y cells. Cell viability, nuclear morphology, and mitochondrial membrane potential were then detected, and the expression of alpha-synuclein, cytochrome c, Bcl-2 and Bax were analyzed by Western blotting. The results showed that after exposure to 500 microM MPP(+) for 24 h, about 41.0+/-1.5% control cells showed low mitochondrial membrane potential. However, the percentage was 13.6+/-1.2% in MPP(+) treated alpha-synuclein knockdown cells. MPP(+) induced cytochrome c release significantly, which was about 3.1-fold compared with that of control. However, in alpha-synuclein knockdown cells, the release of cytochrome c was blocked, which was about 1.4-fold compared with that of control. The Bcl-2/Bax ratio of SH-SY5Y cells reduced to 35.5+/-3.8% after MPP(+) treatment, and this ratio was 85.2+/-3.0% in MPP(+) treated alpha-synuclein knockdown cells. These data suggest that knockdown of alpha- synuclein might be an effective means in rescuing MPP(+)-induced mitochondrial dysfunction of SH-SY5Y cells. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/19646423/Alpha_synuclein_knockdown_attenuates_MPP+_induced_mitochondrial_dysfunction_of_SH_SY5Y_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(09)01515-7 DB - PRIME DP - Unbound Medicine ER -