Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin fibroblasts.
Oxidative stress of human skin fibroblasts by treatment with ultraviolet A (UVA) radiation has been shown to lead to an increase in levels of the heme catabolizing enzyme heme oxygenase 1 [heme, hydrogen-donor:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating), EC 1.14.99.3] and the iron storage protein ferritin. Here we show that human skin fibroblasts, preirradiated with UVA, sustain less membrane damage during a subsequent exposure to UVA radiation than cells that had not been preirradiated. Pretreating cells with heme oxygenase 1 antisense oligonucleotide inhibited the irradiation-dependent induction of both the heme oxygenase I enzyme and ferritin and abolished the protective effect of preirradiation. Inhibition of the UVA preirradiation-dependent increase in ferritin, but not heme oxygenase, with desferrioxamine also abolished the protection. This identifies heme oxygenase 1 as a crucial enzymatic intermediate in an oxidant stress-inducible antioxidant defense mechanism, involving ferritin, in human skin fibroblasts.
Vile
G F
GF
Swiss Institute for Experimental Cancer Research, ISREC, Lausanne.
Basu-Modak
S
S
Waltner
C
C
Tyrrell
R M
RM
D000222:Adaptation, Physiological; D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects / Q000528:radiation effects; D005293:Ferritins / Q000096:biosynthesis*; D005347:Fibroblasts / Q000201:enzymology / Q000528:radiation effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010084:Oxidation-Reduction; D012867:Skin / Q000201:enzymology / Q000528:radiation effects*; D014466:Ultraviolet Rays
D000975:Antioxidants; D016376:Oligonucleotides, Antisense; D005293:Ferritins; D006419:Heme Oxygenase (Decyclizing); D003676:Deferoxamine