Myeloid cell leukemia 1 (Mcl-1) protects against 1-methyl-4-phenylpyridinium ion (MPP plus ) induced apoptosis in Parkinson's disease
Myeloid cell leukemia 1 (Mcl-1) protects against 1-methyl-4-phenylpyridinium ion (MPP plus ) induced apoptosis in Parkinson's disease
复制标题
DOI：
10.1007/s11011-015-9703-z
复制
发表时间：
2015-10-01
影响因子：
3.6
通讯作者：
Du, Zhongde
中科院分区：
文献类型：
--
作者：
Fan, Lijing;Jiang, Li;Du, Zhongde
髓系细胞白血病1(Mcl(-1))是Bcl2家族中的抗凋亡成员，在保护细胞免受凋亡中起着重要作用。Mcl(-1)在帕金森病(PD)中的表达模式和可能的作用尚不清楚。在本研究中，我们的结果表明，1-甲基-4-苯基吡啶(MPP+)处理可剂量依赖地增强SH-SY5Y细胞Mcl(-1)在信使RNA和蛋白水平的表达。此外，我们还观察到在MPP+作用下，Elk-1在Ser383位的磷酸化水平以及Elk-1的核转位增加。重要的是，MPP+诱导的Mcl(-1)表达上调可被ELK-1基因敲除。小分子RNA对Mcl(-1)的抑制作用可加剧MPP+诱导的LDH释放。此外，Hoechst 33,258核染色结果显示，与对照组相比，沉默Mcl(-1)诱导的细胞凋亡率显著增加。在机械上，MPP+处理的细胞中裂解的Caspase3和PARP水平升高，而Mcl(-1)的敲除加剧了这一现象。这些发现提示Mcl(-1)可能是帕金森病治疗的潜在靶点。
The myeloid cell leukemia 1 (Mcl(-1)) is an anti-apoptotic member of the Bcl-2 family, which plays an essential role in protecting cells against apoptosis. The expression pattern and potential roles of Mcl(-1) in Parkinson's diseases (PD) are still unknown. In this study, our results indicated that 1-methyl-4-phenylpyridinium (MPP+) treatment augmented the expression of Mcl(-1) at both messenger RNA (mRNA) and protein levels in a dose-dependent manner in SH-SY5Y cells. Moreover, we observed increased phosphorylation of Elk-1at Ser383 as well as nuclear translocation of Elk-1 in exposure to MPP+ treatment. Importantly, the elevated expression of Mcl(-1) induced by MPP+ was abolished by knockdown of Elk-1. It was also found that inhibition of Mcl(-1) by small RNA transfection exacerbates MPP + -induced LDH release after 48 h incubation. In addition, Hoechst 33,258 nuclear staining results demonstrated that silence of Mcl(-1) induced a significant increase in apoptosis in cells when compared with the control condition. Mechanistically, the levels of cleaved Caspase3 and PARP were elevated in MPP+ treated cells, which was exacerbated by knockdown of Mcl(-1). These findings suggest that Mcl(-1) might be a potential therapeutic target for PD treatment.