Ooe Hiromasa, Taira Takahiro, Iguchi-Ariga Sanae M M, Ariga Hiroyoshi
Graduate School of Pharmaceutical Sciences, Graduate School of Agriculture, Hokkaido University, Sapporo 060-0812, Japan.
Toxicol Sci. 2005 Nov;88(1):114-26. doi: 10.1093/toxsci/kfi278. Epub 2005 Aug 10.
DJ-1 was first identified as an activated ras-dependent oncogene. DJ-1 is related to male fertility, and its expression in sperm decreases in response to exposure to a number of reproductive toxicants. DJ-1 has been associated with the onset of familial Parkinson's disease (PD) in humans, and has been found to have activity against oxidative damage by eliminating reactive oxygen species (ROS). In this study, we investigated the role of DJ-1 in oxidative stresses by administration of bisphenol A (BPA), which has been reported to induce oxidative stress in rodents, to male mice and cultured cells. In male mice, we found that BPA significantly increased the expression level of DJ-1 in the sperm and brain. In cultured Neuro2a and GC1 cells, we found that BPA induced ROS production and significantly compromised mitochondrial function concomitant with elevated expression and oxidization of DJ-1. DJ-1 was found to maintain the complex I activity against BPA-induced oxidative stress after the localization in mitochondria. The results showed that DJ-1 plays a role in the prevention of mitochondrial injury-induced cell death.
DJ-1最初被鉴定为一种活化的ras依赖性癌基因。DJ-1与男性生育能力有关，在暴露于多种生殖毒物后，其在精子中的表达会降低。DJ-1与人类家族性帕金森病（PD）的发病有关，并且已发现它通过消除活性氧（ROS）具有抗氧化损伤的活性。在本研究中，我们通过给雄性小鼠和培养细胞施用双酚A（BPA）来研究DJ-1在氧化应激中的作用，据报道BPA可在啮齿动物中诱导氧化应激。在雄性小鼠中，我们发现BPA显著增加了精子和大脑中DJ-1的表达水平。在培养的Neuro2a和GC1细胞中，我们发现BPA诱导ROS产生，并伴随着DJ-1表达升高和氧化，显著损害线粒体功能。在定位于线粒体后，发现DJ-1可维持针对BPA诱导的氧化应激的复合物I活性。结果表明，DJ-1在预防线粒体损伤诱导的细胞死亡中发挥作用。
