Department of Biochemical and Molecular Biology, China Medical University, Shenyang City 110001, Liaoning Province, China.
Brain Res Bull. 2010 Mar 16;81(4-5):428-33. doi: 10.1016/j.brainresbull.2009.11.007. Epub 2009 Nov 20.
Chronic inorganic manganese (Mn) exposure has been known to induce neurological disorders similar to Parkinson's disease (PD). Apoptosis has been shown to be involved in manganese-induced neurotoxicity. However, the up-stream molecular mechanisms for cell apoptosis are not established. alpha-Synuclein (alpha-syn) is a major component of intracellular inclusions in PD, Alzheimer's disease (AD), and other neurodegenerative disorders. We investigated the role of alpha-syn in manganese chloride (MnCl(2))-induced apoptosis. Results show that MnCl(2) enhanced transcriptional and translational alpha-syn overexpression, and apoptosis as measured by caspase-3 activity and flow cytometry. Overexpressing alpha-syn exacerbated manganese-induced apoptosis, whereas antisense alpha-syn treatment significantly reversed MnCl(2)-induced apoptosis in human neuroblastoma SH-SY5Y cells. In conclusion, our results imply that intracellular alpha-syn overexpression may be responsible for MnCl(2)-induced apoptosis.
慢性无机锰（Mn）暴露已被证实可引起类似于帕金森病（PD）的神经紊乱。细胞凋亡已被证实与锰诱导的神经毒性有关。然而，细胞凋亡的上游分子机制尚未确定。α-突触核蛋白（α-syn）是帕金森病、阿尔茨海默病（AD）和其他神经退行性疾病中细胞内包涵体的主要成分。我们研究了α-syn 在氯化锰（MnCl2）诱导的细胞凋亡中的作用。结果表明，MnCl2 增强了 α-syn 的转录和翻译过表达，以及通过 caspase-3 活性和流式细胞术测量的细胞凋亡。过表达 α-syn 加剧了锰诱导的细胞凋亡，而反义 α-syn 处理则显著逆转了 MnCl2 在人神经母细胞瘤 SH-SY5Y 细胞中的诱导凋亡。总之，我们的结果表明，细胞内 α-syn 的过表达可能是 MnCl2 诱导细胞凋亡的原因。
