title: Depletion of glutathione does not affect electron transport chain complex activity in brain mitochondria: Implications for Parkinson 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 disease patients. In postmortem analysis, measurement of glutathione levels and complex I activity can be delayed up to 20h. We investigated whether depletion of glutathione in the preweanling rat induces a reduction in complex I activity in brain mitochondria and the effects that postmortem delay has on glutathione levels and electron transport chain activity. After injection with the glutamate-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 24h, in which animals were kept at 4°C, the 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, or IV activity in either group. These results suggest that a preexisting deficiency of glutathione or a loss of glutathione during postmortem delay does not influence mitochondrial respiratory chain activity in the brain.
authors.affiliation: Clinical and Molecular Genetics Unit, University College London Institute of Child Health, London WC1N 1EH, UK.
authors.forename: Simon J R
authors.initials: SJ
authors.lastname: Heales
authors.forename: Adrian
authors.initials: A
authors.lastname: Menzes
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Davey
mesh_terms: D000818:Animals; D000833:Animals, Suckling / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000008:administration & dosage; D002478:Cells, Cultured; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005978:Glutathione / Q000172:deficiency; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000378:metabolism; D011180:Postmortem Changes; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D042967:Electron Transport Complex I; D005978:Glutathione