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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-9-7
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1872-6240
pubmed:author
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
1292
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-9
pubmed:meshHeading
pubmed-meshheading:19646423-1-Methyl-4-phenylpyridinium, pubmed-meshheading:19646423-Cell Line, Tumor, pubmed-meshheading:19646423-Cell Nucleus Shape, pubmed-meshheading:19646423-Cell Survival, pubmed-meshheading:19646423-Central Nervous System Agents, pubmed-meshheading:19646423-Cytochromes c, pubmed-meshheading:19646423-Gene Knockdown Techniques, pubmed-meshheading:19646423-Humans, pubmed-meshheading:19646423-Inverted Repeat Sequences, pubmed-meshheading:19646423-Membrane Potential, Mitochondrial, pubmed-meshheading:19646423-Mitochondria, pubmed-meshheading:19646423-Mitochondrial Diseases, pubmed-meshheading:19646423-Neurons, pubmed-meshheading:19646423-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:19646423-RNA, Messenger, pubmed-meshheading:19646423-alpha-Synuclein, pubmed-meshheading:19646423-bcl-2-Associated X Protein
pubmed:year
2009
pubmed:articleTitle
Alpha-synuclein knockdown attenuates MPP+ induced mitochondrial dysfunction of SH-SY5Y cells.
pubmed:affiliation
Department of Anatomy, Shandong University School of Medicine, 44 Wen-hua Xi Road, Jinan, Shandong Province 250012, PR China.
pubmed:publicationType
Journal Article