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Deng H, Jankovic J, Guo Y, Xie W, Le W: Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5Y. Biochem Biophys Res Commun. 2005 Dec 2;337(4):1133-8. Epub 2005 Oct 6.
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. |
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