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Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5YBiochemical and Biophysical Research Communications, Vol. 337, No. 4. (02 December 2005), pp. 1133-1138.
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AbstractPTEN-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.
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