Induction of the heme oxygenase gene in human skin fibroblasts by hydrogen peroxide and UVA (365 nm) radiation: evidence for the involvement of the hydroxyl radical.
The induction of heme oxygenase by both hydrogen peroxide and UVA (365 nm) radiation in normal human skin fibroblasts is prevented by prior treatment of cells with the specific iron chelators, o-phenanthroline or desferrioxamine. In addition, both iron chelators protected cells against the lethal effects of H2O2 treatment or UVA irradiation. We propose that the generation of the highly reactive hydroxyl radical by an iron catalyzed Fenton reaction is involved both in the induction of this stress response and, at least in part, in cell killing by the two treatments. These results are also consistent with the idea that the heme oxygenase gene is induced in response to oxidative stress and that its induction may constitute an inducible protective mechanism against oxidative damage induced by both hydrogen peroxide and UVA radiation.
Keyse
S M
SM
Swiss Institute for Experimental Cancer Research, Epalinges.
Tyrrell
R M
RM
D002470:Cell Survival / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006878:Hydroxides; D017665:Hydroxyl Radical; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010618:Phenanthrolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000166:cytology*; D014466:Ultraviolet Rays
D006878:Hydroxides; D010618:Phenanthrolines; D012333:RNA, Messenger; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D003676:Deferoxamine; C025205:1,10-phenanthroline