N-t-Butyl Hydroxylamine, a Hydrolysis Product of α-Phenyl-N-t-butyl Nitrone, Is More Potent in Delaying Senescence in Human Lung Fibroblasts
| Autor: | Andres Paler-Martinez, Hani Atamna, Bruce N. Ames |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Senescence
Radical Cytochrome c Group Endogeny Hydroxylamines Biochemistry Antioxidants Nitrone Cyclic N-Oxides chemistry.chemical_compound Hydroxylamine Humans Rhodamine 123 Hydrogen peroxide Lung Molecular Biology Cellular Senescence chemistry.chemical_classification biology Hydrolysis Cytochrome c Hydrogen Peroxide Cell Biology Glutathione Fibroblasts Mitochondria chemistry biology.protein Nitrogen Oxides |
| Zdroj: | Journal of Biological Chemistry. 275:6741-6748 |
| ISSN: | 0021-9258 |
| Popis: | Alpha-phenyl-N-t-butyl nitrone (PBN), a spin trap, scavenges hydroxyl radicals, protects tissues from oxidative injury, and delays senescence of both normal human lung fibroblasts (IMR90) and senescence-accelerated mice. N-t-butyl hydroxylamine and benzaldehyde are the breakdown products of PBN. N-t-Butyl hydroxylamine delays senescence of IMR90 cells at concentrations as low as 10 microM compared with 200 microM PBN to produce a similar effect, suggesting that N-t-butyl hydroxylamine is the active form of PBN. N-Benzyl hydroxylamine and N-methyl hydroxylamine compounds unrelated to PBN were also effective in delaying senescence, suggesting the active functional group is the N-hydroxylamine. All the N-hydroxylamines tested significantly decreased the endogenous production of oxidants, as measured by the oxidation of 2', 7'-dichlorodihydrofluorescin and the increase in the GSH/GSSG ratio. The acceleration of senescence induced by hydrogen peroxide is reversed by the N-hydroxylamines. DNA damage, as determined by the level of apurinic/apyrimidinic sites, also decreased significantly following treatment with N-hydroxylamines. The N-hydroxylamines appear to be effective through mitochondria; they delay age-dependent changes in mitochondria as measured by accumulation of rhodamine-123, they prevent reduction of cytochrome C(FeIII) by superoxide radical, and they reverse an age-dependent decay of mitochondrial aconitase, suggesting they react with the superoxide radical. |
| Databáze: | OpenAIRE |
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