Zhang Jianlei, Liu Wei, Wang Yabo, Zhao Shengnan, Chang Na
Department of Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, China.
Dis Markers. 2017;2017:5806146. doi: 10.1155/2017/5806146. Epub 2017 Apr 17.
miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson's disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3 (GSK3) was upregulated at mRNA and protein levels in MPP-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF- and IL-1 in SH-SY5Y cells in the presence of MPP. Luciferase reporter assay demonstrated that GSK3 was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3 activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3 in MPP-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.
据报道，miR-135a-5p通过靶向rho相关蛋白激酶2（ROCK2）在硫化氢对帕金森病（PD）的保护作用中发挥关键作用。然而，miR-135家族的另一个成员（miR-135b）在PD中的作用及其潜在机制仍不清楚。qRT-PCR和蛋白质印迹显示，在MPP诱导中毒的SH-SY5Y细胞中，miR-135在mRNA和蛋白质水平上呈剂量和时间依赖性下调，糖原合酶激酶3（GSK3）上调。MTT、TUNEL和ELISA分析显示，在存在MPP的情况下，miR-135b过表达显著促进SH-SY5Y细胞的增殖，抑制细胞凋亡以及TNF-和IL-1的产生。荧光素酶报告基因检测表明GSK3是miR-135b的直接靶点。此外，GSK3激活剂硝普钠（SNP）显著逆转了miR-135b上调对MPP诱导中毒的SH-SY5Y细胞的增殖、凋亡和炎性细胞因子产生的影响。综上所述，miR-135b通过靶向GSK3促进MPP诱导中毒的SH-SY5Y细胞增殖、抑制细胞凋亡和神经炎症，发挥保护作用，为PD的治疗提供了一个潜在的治疗靶点。
