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Nitric oxide protects against mitochondrial permeabilizastion induced by gluthathione depletion: role of S-nitrosylation?
journal contribution
posted on 2006-01-06, 00:00 authored by M Whiteman, Y Chua, D Zhang, Wei DuanWei Duan, Y C Liou, J ArmstrongNitric oxide (NO) is known to mediate a multitude of biological effects including inhibition of respiration at cytochrome c oxidase (COX), formation of peroxynitrite (ONOO−) by reaction with mitochondrial superoxide (O2• −), and S-nitrosylation of proteins. In this study, we investigated pathways of NO metabolism in lymphoblastic leukemic CEM cells in response to glutathione (GSH) depletion. We found that NO blocked mitochondrial protein thiol oxidation, membrane permeabilization, and cell death. The effects of NO were: (1) independent of respiratory chain inhibition since protection was also observed in CEM cells lacking mitochondrial DNA (ρ0) which do not possess a functional respiratory chain and (2) independent of ONOO− formation since nitrotyrosine (a marker for ONOO− formation) was not detected in extracts from cells treated with NO after GSH depletion. However, NO increased the level of mitochondrial protein S-nitrosylation (SNO) determined by the Biotin Switch assay and by the release of NO from mitochondrial fractions treated with mercuric chloride (which cleaves SNO bonds to release NO). In conclusion, these results indicate that NO blocks cell death after GSH depletion by preserving the redox status of mitochondrial protein thiols probably by a mechanism that involves S-nitrosylation of mitochondrial protein thiols.
History
Journal
Biochemical and biophysical research comminicationsVolume
339Issue
1Pagination
255 - 262Publisher
Academic PressLocation
San Diego Calif.Publisher DOI
ISSN
0006-291XeISSN
1090-2104Language
engPublication classification
C1.1 Refereed article in a scholarly journal; C Journal articleCopyright notice
2005, Elsevier Inc.Usage metrics
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No categories selectedKeywords
nitric oxideglutathioneS-nitrosylationmitochondrial membrane permeabilizationperoxynitritesuperoxidenitrotyrosinereactive oxygen speciesScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyBiophysicsCYTOCHROME-C-OXIDASEINHIBITIONNOBIOCHEMISTRYACTIVATIONMECHANISMOXIDATIONENZYME
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