Depletion of glutathione does not affect electron transport chain complex activities in brain mitochondria: Implications for Parkinsons's disease and postmortem studies

Abstract

Glutathione is an important antioxidant in the brain that appears to be decreased, in conjunction with mitochondrial complex I activity, in Parkinson?s disease patients. In postmortem analysis, measurement of glutathione levels and complex I activity can be delayed up to 20 h. We investigated if depletion of glutathione in the pre-weanling rat induces a reduction in complex I activity in brain mitochondria and the effect that postmortem delay has on glutathione levels and electron transport chain activities. Following injection with the gamma-glutamyl cysteine ligase inhibitor, buthionine sulfoximine (L-BSO), glutathione levels were decreased by 53% compared to the control values in whole brain homogenates. During postmortem delay of 24 hours, in which animals were kept at 4?C, levels of glutathione decreased in the control group by 58% and in the L-BSO treated group by 79%. However, during this period, there were no changes in mitochondrial electron transport chain complex I, II-III and IV activities in either group. These results suggest that a pre-existing deficiency of glutathione or a loss of glutathione during postmortem delay does not influence mitochondrial respiratory chain activities in the brain.