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Depletion of glutathione up‐regulates mitochondrial complex I expression in glial cells
Author(s) -
Vásquez Osmán L.,
Almeida Ángeles,
Bolaños Juan P.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00223.x
Subject(s) - glutathione , buthionine sulfoximine , neuroglia , biology , mitochondrion , oxidative stress , microbiology and biotechnology , protein subunit , astrocyte , glutathione synthetase , northern blot , biochemistry , gene expression , gene , endocrinology , central nervous system , enzyme
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 γ‐glutamylcysteine synthetase inhibitor l ‐buthionine‐( S , R )‐sulfoximine ( l ‐BSO; 0.1–1 m m ) 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 m m ) 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.