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N‐ t ‐Butyl hydroxylamine is an antioxidant that reverses age‐related changes in mitochondria in vivo and in vitro
Author(s) -
Atamna Hani,
Robinson Charles,
Ingersoll Russell,
Elliott Heather,
Ames Bruce N.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0134com
Subject(s) - mitochondrion , senescence , in vivo , in vitro , antioxidant , hydroxylamine , chemistry , extracellular , oxidative phosphorylation , microbiology and biotechnology , biochemistry , biology
N‐ t ‐butyl hydroxylamine (NtBHA) delays senescence‐dependent changes in human lung fibroblasts (IMR90) (Atamna et al., J. Biol Chem. 275, 6741–6748). The current study examines the effect of NtBHA on mitochondria in old and young rats and human primary fibroblasts (IMR90). In NtBHA‐treated rats, the age‐dependent decline in food consumption and ambulatory activity was reversed without affecting body weight. The respiratory control ratio of mitochondria from liver of old rats improved after feeding NtBHA. These findings suggest that NtBHA improved mitochondrial function in vivo. The age‐dependent increase in proteins with thiol‐mixed disulfides was significantly lower in old rats treated with NtBHA. NtBHA was effective only in old rats;no significant effect was observed in young rats. In IMR90 cells, NtBHA delayed senescence‐associated changes in mitochondria and cellular senescence induced by maintaining the cells under suboptimal levels of growth factors. Proteasomal activity was also higher in cells treated with NtBHA than in untreated cells. NtBHA accumulates in cells 10‐ to15‐fold the extracellular concentration and is maintained by mitochondrial NADH. NtBHA is an antioxidant that is recycled by mitochondrial electron transport chain and prevents radical‐induced toxicity to mitochondria.—Atamna, H., Robinson, C., Ingersoll, R., Elliott, H., Ames, B. N. N‐ t ‐Butyl hydroxylamine is an antioxidant that reverses age‐related changes in mitochondria in vivo and in vitro. FASEB J. 15, 2196–2204 (2001)