Abstract
PTEN-induced kinase 1 (PINK1) is a recently identified gene, mutations of which cause levodopa-responsive parkinsonism. An over-expression of wild-type PINK1 protects neurons from stress-induced mitochondrial dysfunction and apoptosis. We studied the effects of PINK1 suppression using small interfering RNA (siRNA), which can inhibit PINK1 mRNA expression up to 87%, and decrease PINK1 protein up to 80% in human dopaminergic cell line SH-SY5Y. Incubation with PINK1 siRNA decreased SH-SY5Y cell viability and significantly increased MPP(+) or rotenone-induced cytotoxicity. Our results indicate that reduction in PINK1 expression can trigger apoptotic process that can be exacerbated by the presence of MPP(+) or rotenone. These findings support the hypothesis that PINK1 participates in the protection of dopaminergic neurons.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Apoptosis*
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Base Sequence
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Cell Line, Tumor
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Cloning, Molecular
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Dopamine / biosynthesis
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Dopamine / metabolism*
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Gene Expression
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Humans
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Molecular Sequence Data
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Neurons / metabolism*
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Neurons / pathology*
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Peptide Elongation Factor 1
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Peptide Elongation Factors / chemistry
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Peptide Elongation Factors / metabolism
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Protein Kinases / genetics*
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Protein Kinases / metabolism*
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RNA Interference
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae / chemistry
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
Substances
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CAM1 protein, S cerevisiae
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Peptide Elongation Factor 1
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Peptide Elongation Factors
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RNA, Small Interfering
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Protein Kinases
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PTEN-induced putative kinase
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Dopamine