title: The protective role of cellular glutathione peroxidase against trauma-induced mitochondrial dysfunction in the mouse brain.
abstract: Reactive oxygen species are believed to participate in the pathogenesis of traumatic brain injury (TBI). To evaluate the role of cellular glutathione peroxidase (Gpx1), a selenium-containing enzyme functioning in reduction of hydrogen peroxide and alkyl hyperoxides, in protecting animals against TBI, a line of Gpx1 transgenic mice was generated. Overexpression of Gpx1 was found in many organs including the brain of the transgenic mice. This line of transgenic mice and knockout mice deficient in Gpx1 were used in a model of controlled cortical impact injury and the efficiency of oxidative phosphorylation in brain mitochondria was determined. Although a 2-mm depth of mechanical impact caused a drastic decrease in NAD-linked electron transfer activities and energy-coupling capacities in brain mitochondria of nontransgenic mice, the decrease in mitochondrial function was completely prevented by overexpression of Gpx1 in Gpx1 transgenic mice. In addition, a 1-mm deformation depth hardly affected brain mitochondrial function in wild-type (Gpx1+/+) mice, yet resulted in a significant decrease in mitochondrial bioenergetic capacity in brains of homozygous Gpx1 knockout (Gpx1-/-) mice. Further experiments showed that inclusion of calcium chelator egtazic acid in measurement of mitochondrial respiration could completely restore the efficiency of mitochondrial respiration in injured brains of nontransgenic mice and Gpx1-/- mice, suggesting that the observed mitochondrial dysfunction is a direct result of increase in mitochondrion-associated calcium, which is secondary to the increased oxidative stress. These studies not only establish the role of Gpx1 in preventing mitochondrial dysfunction in mouse brain after TBI, but also suggest the species of reactive oxygen responsible for this event.
authors: Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan 48201, USA.
authors: Ye
authors: Y
authors: Xiong
authors: Feng-Shiun
authors: FS
authors: Shie
authors: Jing
authors: J
authors: Zhang
authors: Chuan-Pu
authors: CP
authors: Lee
authors: Ye-Shih
authors: YS
authors: Ho