Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Neurochem. 2011 Feb;116(3):334-41. doi: 10.1111/j.1471-4159.2010.07112.x. Epub 2010 Dec 22.
We previously observed marked down-regulation of the mRNA for angiogenin, a potent inducer of neovascularization, in a mouse model of Parkinson's disease (PD) based on over-expression of alpha-synuclein. Angiogenin has also been recently implicated in the pathogenesis of amyotrophic lateral sclerosis. In this study, we confirmed that mouse angiogenin-1 protein is dramatically reduced in this transgenic alpha-synuclein mouse model of PD, and examined the effect of angiogenin in cellular models of PD. We found that endogenous angiogenin is present in two dopamine-producing neuroblastoma cell lines, SH-SY5Y and M17, and that exogenous angiogenin is taken up by these cells and leads to phosphorylation of Akt. Applied angiogenin protects against the cell death induced by the neurotoxins 1-methyl-4-phenylpyridinium and rotenone and reduces the activation of caspase 3. Together our data supports the importance of angiogenin in protecting against dopaminergic neuronal cell death and suggests its potential as a therapy for PD.
我们之前观察到，在基于α-突触核蛋白过表达的帕金森病（PD）小鼠模型中，血管生成素的 mRNA 表达明显下调，血管生成素是一种强烈的促血管新生诱导剂。血管生成素最近也被牵连到肌萎缩性侧索硬化症的发病机制中。在这项研究中，我们证实了在这种转基因α-突触核蛋白 PD 小鼠模型中，鼠血管生成素-1 蛋白显著减少，并研究了血管生成素在 PD 细胞模型中的作用。我们发现，内源性血管生成素存在于两种多巴胺产生的神经母细胞瘤细胞系 SH-SY5Y 和 M17 中，并且外源性血管生成素被这些细胞摄取，并导致 Akt 的磷酸化。应用血管生成素可防止神经毒素 1-甲基-4-苯基吡啶和鱼藤酮诱导的细胞死亡，并减少 caspase 3 的激活。我们的数据共同支持了血管生成素在保护多巴胺能神经元细胞死亡中的重要性，并表明其作为 PD 治疗的潜力。
