title: Involvement of reactive oxygen species derived from mitochondria in neuronal injury elicited by methylmercury.
abstract: Methylmercury induces oxidative stress and subsequent neuronal injury. However, the mechanism by which methylmercury elicits reactive oxygen species (ROS) production remains under debate. In this study, we investigated the involvement of mitochondrial ROS in methylmercury-induced neuronal cell injury using human neuroblastoma SH-SY5Y-derived ρ0cells, which have a deletion of mitochondrial DNA and thus decreased respiratory activity. SH-SY5Y cells were cultured for 60 days in the presence of ethidium bromide to produce ρ0cells. Our ρ0cells showed decreases in the cytochromecoxidase expression and activity as well as oxygen consumption compared with original SH-SY5Y cells. Methylmercury at a concentration of 1 µM induced cell death with oxidative stress in original SH-SY5Y cells, but not ρ0cells, indicating that ρ0cells are resistant to methylmercury-induced oxidative stress. ρ0cells also showed tolerance against hydrogen peroxide and superoxide anion, suggesting that ρ0cells are resistant to total ROS. These data indicate that mitochondrial ROS are clearly involved in oxidative stress and subsequent cell death induced by methylmercury. Considering that the dominant mechanism of ROS generation elicited by methylmercury is due to direct antioxidant enzyme inhibition, mitochondria might play a role in amplifying ROS in methylmercury-induced neurotoxicity.
authors.affiliation: Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima 739-8521, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ishihara
authors.affiliation: Department of Environmental Health, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Environmental Health, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima 739-8521, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
keywords: methylmercury; mitochondria; neurotoxicity; reactive oxygen species; ρ0 cells