Changes in selenoprotein P in substantia nigra and putamen in Parkinson's disease.
Changes in selenoprotein P in substantia nigra and putamen in Parkinson's disease.
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DOI：
10.3233/jpd-2012-11052
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Berry MJ
中科院分区：
文献类型：
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作者：
Bellinger FP;Raman AV;Rueli RH;Bellinger MT;Dewing AS;Seale LA;Andres MA;Uyehara-Lock JH;White LR;Ross GW;Berry MJ
氧化应激和氧化多巴胺参与了帕金森病（PD）黑质纹状体通路的变性。硒蛋白是以硒代半胱氨酸的形式含有硒元素的蛋白质家族，其中许多蛋白质具有抗氧化功能。我们最近报道了硒蛋白、磷脂氢过氧化物谷胱甘肽过氧化物酶GPX 4及其与神经黑色素在PD脑中的共定位表达的变化。为了进一步了解GPX 4在帕金森病中的变化，我们在这里研究了硒转运蛋白硒蛋白P（Sepp 1）在死后帕金森病脑组织中的表达。中脑Sepp 1在黑质（SN）的神经元中表达，并且表达集中在路易体中心，这是PD的病理标志。与GPX 4一样，与对照组相比，PD受试者的SN中Sepp 1表达显著降低，但相对于细胞密度增加。在壳核，Sepp 1被发现在细胞体和多巴胺能轴突和终端，虽然Sepp 1的水平没有改变PD受试者相比，对照组。Sepp 1和GPX 4的表达水平在对照受试者的壳核中强烈相关，但在PD受试者的壳核中不相关。这些发现表明Sepp 1在黑质纹状体通路中的作用，并表明Sepp 1在纹状体中的局部释放可能对于其他硒蛋白（例如GPX 4）的信号传导和/或合成很重要。
Oxidative stress and oxidized dopamine contribute to the degeneration of the nigrostriatal pathway in Parkinson’s disease (PD). Selenoproteins are a family of proteins containing the element selenium in the form of the amino acid selenocysteine, and many of these proteins have antioxidant functions. We recently reported changes in expression of the selenoprotein, phospholipid hydroperoxide glutathione peroxidase GPX4 and its co-localization with neuromelanin in PD brain. To further understand the changes in GPX4 in PD, we examine here the expression of the selenium transport protein selenoprotein P (Sepp1) in postmortem Parkinson’s brain tissue. Sepp1 in midbrain was expressed in neurons of the substantia nigra (SN), and expression was concentrated within the centers of Lewy bodies, the pathological hallmark of PD. As with GPX4, Sepp1 expression was significantly reduced in SN from PD subjects compared with controls, but increased relative to cell density. In putamen, Sepp1 was found in cell bodies and in dopaminergic axons and terminals, although levels of Sepp1 were not altered in PD subjects compared to controls. Expression levels of Sepp1 and GPX4 correlated strongly in the putamen of control subjects but not in the putamen of PD subjects. These findings indicate a role for Sepp1 in the nigrostriatal pathway, and suggest that local release of Sepp1 in striatum may be important for signaling and/or synthesis of other selenoproteins such as GPX4.