Deng Hao, Jankovic Joseph, Guo Yi, Xie Wenjie, Le Weidong
Department of Neurology, Baylor College of Medicine, USA.
Biochem Biophys Res Commun. 2005 Dec 2;337(4):1133-8. doi: 10.1016/j.bbrc.2005.09.178. 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.
PTEN诱导激酶1（PINK1）是最近发现的一个基因，其突变会导致左旋多巴反应性帕金森综合征。野生型PINK1的过表达可保护神经元免受应激诱导的线粒体功能障碍和细胞凋亡。我们使用小干扰RNA（siRNA）研究了PINK1抑制的作用，siRNA可将人多巴胺能细胞系SH-SY5Y中的PINK1 mRNA表达抑制高达87%，并将PINK1蛋白降低高达80%。用PINK1 siRNA孵育会降低SH-SY5Y细胞活力，并显著增加MPP(+)或鱼藤酮诱导的细胞毒性。我们的结果表明，PINK1表达降低可触发凋亡过程，而MPP(+)或鱼藤酮的存在会加剧这一过程。这些发现支持了PINK1参与保护多巴胺能神经元的假说。
