Paper
N-t-Butyl Hydroxylamine, a Hydrolysis Product of α-Phenyl-N-t-butyl Nitrone, Is More Potent in Delaying Senescence in Human Lung Fibroblasts*
Published Mar 10, 2000 · H. Atamna, A. Paler-Martinez, B. Ames
The Journal of Biological Chemistry
139
Citations
8
Influential Citations
Abstract
α-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 μm compared with 200 μm PBN to produce a similar effect, suggesting thatN-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 theN-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 withN-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 CFeIII by superoxide radical, and they reverse an age-dependent decay of mitochondrial aconitase, suggesting they react with the superoxide radical.
In Vitro Study
Highly CitedN-t-Butyl hydroxylamine, a breakdown product of -Phenyl-N-t-butyl nitrone, is more potent in delaying senescence in human lung fibroblasts than PBN itself, suggesting it is the active form of PBN.
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