title: Glutathione depletion in antioxidant defense of differentiated NT2-LHON cybrids.
abstract: The mechanism of retinal ganglion cell loss in Leber's hereditary optic neuropathy (LHON) is still uncertain, and a role of enhanced superoxide production by the mutant mitochondrial complex I has been hypothesized. In the present study, it was shown that LHON cybrids, carrying the np11778 mutation, became selectively more H(2)O(2) sensitive compared with the parental cell line only following short-term retinoic acid differentiation. They contained a decreased cellular glutathione pool (49%, p< or =0.05), despite 1.5-fold enhanced expression of the regulatory subunit of gamma-glutamylcysteine synthetase (p< or =0.05). This points to a reduction of the capacity to detoxify H(2)O(2) and to changes in thiol redox potential. The activity of the H(2)O(2) degrading enzyme glutathione peroxidase (GPx) and the activities of glutathione reductase (GR) and superoxide dismutase (SOD) were unaffected.
authors.affiliation: Department of Neuropathology, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schoeler
authors.forename: K
authors.initials: K
authors.lastname: Winkler-Stuck
authors.forename: R
authors.initials: R
authors.lastname: Szibor
authors.forename: M F
authors.initials: MF
authors.lastname: Haroon
authors.forename: F N
authors.initials: FN
authors.lastname: Gellerich
authors.forename: K
authors.initials: K
authors.lastname: Chamaon
authors.forename: C
authors.initials: C
authors.lastname: Mawrin
authors.forename: E
authors.initials: E
authors.lastname: Kirches
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D042967:Electron Transport Complex I / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D017354:Point Mutation; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013724:Teratoma; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D016877:Oxidants; D014212:Tretinoin; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D042967:Electron Transport Complex I; D005978:Glutathione