Health Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Kansai Center, Ikeda, Osaka, Japan.
Free Radic Res. 2010 Apr;44(4):410-21. doi: 10.3109/10715760903536349.
The present study performed proteomic analysis of the midbrain and striatum of 6-hydroxydopamine (6-OHDA)-treated neonatal rats--a model of attention-deficit hyperactivity disorder (ADHD). Proteomic analysis revealed that a 58-kDa glucose-regulated protein (Grp58) was temporarily phosphorylated and its level was elevated by 6-OHDA. Furthermore, 6-OHDA increased the expression level of C/EBP homologous protein (CHOP), a mediator of endoplasmic reticulum (ER) stress response, in the midbrain and striatum. In vitro experiments using PC12 cells revealed that 6-OHDA or hydrogen peroxide could induce the elevation of Grp58 and CHOP. 6-OHDA could induce the elevation of Grp58 and CHOP in the presence of catalase, a hydrogen peroxide-removing enzyme, suggesting that the elevation of Grp58 and CHOP are induced by both hydrogen peroxide and p-quinone generated by 6-OHDA. Collectively, these findings suggest that ER stress involving the alteration of Grp58 and CHOP play a significant role in the induction of insults by 6-OHDA in vivo.
本研究对 6-羟多巴胺（6-OHDA）处理的新生大鼠的中脑和纹状体进行了蛋白质组学分析——这是一种注意力缺陷多动障碍（ADHD）的模型。蛋白质组学分析显示，一种 58kDa 的葡萄糖调节蛋白（Grp58）被暂时磷酸化，其水平因 6-OHDA 而升高。此外，6-OHDA 增加了中脑和纹状体中内质网（ER）应激反应介质 C/EBP 同源蛋白（CHOP）的表达水平。体外实验使用 PC12 细胞表明，6-OHDA 或过氧化氢可以诱导 Grp58 和 CHOP 的升高。在过氧化氢清除酶（catalase）存在的情况下，6-OHDA 可以诱导 Grp58 和 CHOP 的升高，这表明 Grp58 和 CHOP 的升高是由 6-OHDA 产生的过氧化氢和 p-醌引起的。总之，这些发现表明，涉及 Grp58 和 CHOP 改变的内质网应激在体内 6-OHDA 引起的损伤诱导中起重要作用。
