Otsuki Noriyuki, Homma Takujiro, Fujiwara Hiroki, Kaneko Kenya, Hozumi Yasukazu, Shichiri Mototada, Takashima Mizuki, Ito Junitsu, Konno Tasuku, Kurahashi Toshihiro, Yoshida Yasukazu, Goto Kaoru, Fujii Satoshi, Fujii Junichi
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
Department of Physiology, Yamagata University School of Medicine, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
Regul Toxicol Pharmacol. 2016 Aug;79:83-90. doi: 10.1016/j.yrtph.2016.05.007. Epub 2016 May 7.
Trichloroethylene (TCE) has been implicated as a causative agent for Parkinson's disease (PD). The administration of TCE to rodents induces neurotoxicity associated with dopaminergic neuron death, and evidence suggests that oxidative stress as a major player in the progression of PD. Here we report on TCE-induced behavioral abnormality in mice that are deficient in superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-deficient (Sod1(-/-)) mice were intraperitoneally administered TCE (500 mg/kg) over a period of 4 weeks. Although the TCE-administrated Sod1(-/-) mice showed marked abnormal motor behavior, no significant differences were observed among the experimental groups by biochemical and histopathological analyses. However, treating mouse neuroblastoma-derived NB2a cells with TCE resulted in the down regulation of the SOD1 protein and elevated oxidative stress under conditions where SOD1 production was suppressed. Taken together, these data indicate that SOD1 plays a pivotal role in protecting motor neuron function against TCE toxicity.
三氯乙烯（TCE）被认为是帕金森病（PD）的致病因素。给啮齿动物施用TCE会诱发与多巴胺能神经元死亡相关的神经毒性，并且有证据表明氧化应激是PD进展中的主要因素。在此，我们报告了超氧化物歧化酶1（SOD1）缺陷小鼠中TCE诱导的行为异常。野生型（WT）和SOD1缺陷（Sod1(-/-)）小鼠在4周内腹腔注射TCE（500mg/kg）。尽管给予TCE的Sod1(-/-)小鼠表现出明显的异常运动行为，但通过生化和组织病理学分析在各实验组之间未观察到显著差异。然而，用TCE处理小鼠神经母细胞瘤来源的NB2a细胞导致在SOD1产生受到抑制的条件下SOD1蛋白下调和氧化应激升高。综上所述，这些数据表明SOD1在保护运动神经元功能免受TCE毒性方面起关键作用。
