Depletion of glutathione up-regulates mitochondrial complex I expression in glial cells.
Glutathione deficiency is commonly associated with mitochondrial complex I dysfunction and loss of viability in neurones, but not in glia. In order to address the possible mechanism responsible for this cellular difference, the regulation of mitochondrial complex I expression by glutathione depletion was investigated in glial cells. Incubation of rat-cultured astrocytes and C6 glioma cells with the specific gamma-glutamylcysteine synthetase inhibitor L-buthionine-(S:,R:)-sulfoximine (L-BSO; 0.1-1 mM) decreased the total specific content of glutathione in a dose- and time-dependent fashion. Northern blot analyses revealed that glutathione deficiency caused by L-BSO (0.1 mM) was associated with a twofold enhancement in complex I regulatory subunit ND6 (mitochondrially encoded) mRNA expression after 24-72 h. This effect was accompanied by a twofold increase in complex-I activity at 72 h in L-BSO-treated cells, as compared with control cells, but complex II-III, complex IV and citrate synthase activities were unaltered. It is suggested that the oxidative stress caused by glutathione depletion in glial cells would up-regulate complex-I activity by enhancing the expression of the mitochondrially encoded regulatory subunit. These results could offer further insight into the different degree of cellular susceptibility observed in glial vs. neuronal cells against oxidative stress.
Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Spain.
O L
OL
Vásquez
A
A
Almeida
J P
JP
Bolaños
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000201:enzymology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002478:Cells, Cultured; D002950:Citrate (si)-Synthase / Q000235:genetics; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005910:Glioma; D005978:Glutathione / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D009457:Neuroglia / Q000201:enzymology*; D010088:Oxidoreductases / Q000235:genetics; D016548:Prosencephalon / Q000166:cytology / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013385:Succinate Dehydrogenase / Q000235:genetics; D014407:Tumor Cells, Cultured
D009097:Multienzyme Complexes; D019328:Buthionine Sulfoximine; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I; D005978:Glutathione