Tumor necrosis factor-alpha plus actinomycin D-induced apoptosis of L929 cells is prevented by nitric oxide.
Treatment with the nitric oxide-(NO)-generating compound S-nitroso-N-acetylpenicillamine protected cul-tured L929 cells from apoptosis induced by tumor necrosis factor-alpha (TNF-alpha) plus actinomycin D, as determined by the detection of DNA fragmentation and morphological changes. NO also prevented an enhancement of the production of reactive oxygen intermediates by TNF-alpha plus actinomycin D, as assessed by the oxidation of dihydrorhodamine 123 and hydroethidine. Because the inhibition of mitochondrial respiration by rotenone or antimycin A suppressed the increased oxidation of both dihydrorhodamine 123 and hydroethidine, it was suggested that TNF-alpha accelerated the leakage of reactive oxygen intermediates from the mitochondrial electron transport system. Polarography showed that NO reversibly inhibited mitochondrial respiration at either complexes I-III, II-III, or IV, thus suggesting the inhibition of cytochrome oxidase. Taken together, these findings indicate that the decreased mitochondrial formation of reactive oxygen intermediates in the presence of NO might have a protective effect against TNF-alpha plus actinomycin D-induced apoptosis.
Hakoda
S
S
Department of Emergency, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8507, Japan.
Ishikura
H
H
Takeyama
N
N
Tanaka
T
T
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D019610:Cytoprotection; D003609:Dactinomycin / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D017382:Reactive Oxygen Species; C110881:S-nitro-N-acetylpenicillamine; D014409:Tumor Necrosis Factor-alpha; D012402:Rotenone; D003609:Dactinomycin; D009569:Nitric Oxide; D000968:Antimycin A; D010396:Penicillamine