Sims N R, Anderson M F, Hobbs L M, Powell J A, Zaidan E
Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, South Australia,
Dev Neurosci. 2000 Sep-Dec;22(5-6):366-75. doi: 10.1159/000017462.
During early recirculation following global brain ischemia, mitochondria are exposed to markedly elevated Ca(2+) concentrations and a short-lived production of reactive oxygen species, including hydrogen peroxide (H(2)O(2)). A brief increase in mitochondrial Ca(2+) and a subsequent increase in mitochondrial glutathione content have been observed. In the present study, we have confirmed the increase in mitochondrial glutathione in a rat model of global forebrain ischemia. This change was not inhibited by treatment of the rats with FK506, contrasting with our previous finding that cyclosporin A partially blocked the increase. These results suggest that induction of the mitochondrial permeability transition may be necessary for the increase in glutathione content in these organelles. To further investigate possible mitochondrial responses during early postischemic reperfusion, mitochondria isolated from normal brain were exposed to Ca(2+) and H(2)O(2), under conditions similar to those in intact cells. Respiratory activity was substantially modified when the mitochondria were exposed to Ca(2+) and H(2)O(2) together. Two distinct and largely noninteracting mechanisms apparently accounted for the responses to these agents. The effects of Ca(2+), but not H(2)O(2), were inhibited by cyclosporin A, again implicating the permeability transition in some of the mitochondrial changes.
