Heme oxygenase-1 induction by endogenous nitric oxide: influence of intracellular glutathione.
To investigate the influence of glutathione (GSH) on cellular effects of nitric oxide (NO) formation, human colon adenocarcinoma cells were transfected with a vector allowing controlled expression of inducible nitric oxide synthase (iNOS). Protein levels of oxidative stress-sensitive heme oxygenase-1 (HO-1) were analyzed in the presence or absence of GSH depletion using L-buthionine-[S,R]-sulfoximine and iNOS induction. While no effect was observed in the presence of iNOS activity alone, a synergistic effect on HO-1 expression was observed in the presence of iNOS expression and GSH depletion. This effect was prevented by addition of N-methyl-L-arginine. Therefore, targeting of endogenous NO may be modulated by intracellular GSH.
André
Muriel
M
Institute of Pharmacology and Toxicology, Rue du Bugnon 27, 1005 Lausanne, Switzerland.
Felley-Bosco
Emanuela
E
D001483:Base Sequence; D017931:DNA Primers; D004790:Enzyme Induction; D005978:Glutathione / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D006419:Heme Oxygenase (Decyclizing); D005978:Glutathione