The effects of focal ischemia and reperfusion on the glutathione content of mitochondria from rat brain subregions
Version of Record online: 29 APR 2002
Journal of Neurochemistry
Volume 81, Issue 3, pages 541–549, May 2002
How to Cite
Anderson, M. F. and Sims, N. R. (2002), The effects of focal ischemia and reperfusion on the glutathione content of mitochondria from rat brain subregions. Journal of Neurochemistry, 81: 541–549. doi: 10.1046/j.1471-4159.2002.00836.x
- Issue online: 29 APR 2002
- Version of Record online: 29 APR 2002
- Received September 24, 2001; revised manuscript received December 19, 2001; accepted January 21, 2002.
- focal ischemia;
Glutathione is a key cellular antioxidant that is contained in both cytoplasmic and mitochondrial compartments. Previous investigations indicate that depletion of the mitochondrial pool of glutathione can greatly reduce cell viability. In the present investigation, the effect of focal cerebral ischemia on total (reduced plus oxidized) glutathione in mitochondria was assessed using a rat model of middle cerebral artery occlusion. Total glutathione was substantially decreased in mitochondria prepared from severely ischemic focal tissue in both the cerebral cortex and striatum at 2 h of vessel occlusion and persisted for at least the first 3 h of reperfusion. The loss of mitochondrial glutathione was not associated with decreases of the total tissue glutathione content and was not due to the formation of mixed disulfides with mitochondrial proteins. Thus, an imbalance between uptake and release from the mitochondria in the ischemic tissue provides the most likely explanation for the loss. Decreases in glutathione also developed in mitochondria from the moderately ischemic perifocal tissue when the period of arterial occlusion was extended to 3 h. The presence of mitochondrial glutathione depletion during ischemia showed an apparent close association with the subsequent development of tissue infarction. These findings are consistent with a role for the glutathione depletion in determining the susceptibility of brain tissue to focal ischemia.