title: Prevention of mitochondrial dysfunction in post-traumatic mouse brain by superoxide dismutase.
abstract: Reactive oxygen species (ROS) are known to be involved in the pathogenesis of traumatic brain injury (TBI). Previous studies have shown that the susceptibility of mice to TBI-induced formation of cortical lesion is determined by the expression levels of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD, respectively). However, the underlying biochemical mechanisms are not understood. In this study, we measured the efficiency of mitochondrial respiration in mouse brains with altered expression of these two enzymes. While controlled cortical impact injury (CCII) with a deformation depth of 2 mm caused a drastic decrease in NAD-linked bioenergetic capacity in brain mitochondria of wild-type mice, the functional decrease was not observed in brains of littermate transgenic mice overexpressing CuZnSOD or MnSOD. In addition, a 1 mm CCII greatly compromised brain mitochondrial function in mice deficient in CuZnSOD or MnSOD, but not wild-type mice. Inclusion of the calcium-chelating agent, EGTA, in the assay solution could completely prevent dysfunction of oxidative phosphorylation in all mitochondrial samples, suggesting that the observed impairment of mitochondrial function was a result of calcium overloading. In conclusion, our results imply that mitochondrial dysfunction induced by superoxide anion radical contributes to lesion formation in mouse brain following physical trauma.
authors.affiliation: Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
authors.forename: Feng-Shiun
authors.initials: FS
authors.lastname: Shie
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Chuan-Pu
authors.initials: CP
authors.lastname: Lee
authors.forename: Ye-Shih
authors.initials: YS
authors.lastname: Ho
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D001930:Brain Injuries / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D002118:Calcium; D002614:Chelating Agents; D004533:Egtazic Acid; D009243:NAD; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606291:Sod1 protein, mouse