title: Methylmercury inhibits electron transport chain activity and induces cytochrome c release in cerebellum mitochondria.
abstract: The involvement of oxidative stress has been suggested as a mechanism for toxicity caused by methylmercury (MeHg). One of the major critical sites for oxidative stress is the mitochondria. In this research, to clarify the target site in mitochondria affected by MeHg, the individual activities of the mitochondrial electron transport chain (ETC) (I∼IV) were examined in the liver, cerebrum and cerebellum of MeHg-intoxicated rats. In addition, to elucidate the mechanism underlying MeHg toxicity, cytochrome c release, caspase 3 activity and histological study were examined in the cerebrum and cerebellum. The cerebellum was found to be an exclusive tissue in which significant MeHg-induced alterations were observed. The complex II activity in the cerebellum mitochondria significantly decreased after MeHg exposure. Cytochrome c release from mitochondria increased only in the cerebellum by MeHg exposure. However, no significant alterations in caspase 3 activity or histological structure were found in brain tissues. These results suggest that MeHg acts on the constituents of complex II in the cerebellum, and induces mitochondrial dysfunction, leading to a release of cytochrome c from mitochondria. These events were considered to occur at the early stage of MeHg intoxication.
authors.affiliation: Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1, Kuhonji, Kumamoto 862-0976, Japan. nobuko@kumamoto-u.ac.jp
authors.forename: Nobuko
authors.initials: N
authors.lastname: Mori
authors.forename: Akira
authors.initials: A
authors.lastname: Yasutake
authors.forename: Masumi
authors.initials: M
authors.lastname: Marumoto
authors.forename: Kimiko
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D054022:Cerebrum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045304:Cytochromes c / Q000096:biosynthesis*; D045222:Electron Transport Chain Complex Proteins / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D045222:Electron Transport Chain Complex Proteins; D008767:Methylmercury Compounds; D045304:Cytochromes c; D053148:Caspase 3; C004925:methylmercuric chloride