Abstract
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.
MeSH Terms
Adaptation, Physiological
Antioxidants/metabolism
Cells, Cultured
Deferoxamine/pharmacology
Enzyme Induction/drug effects,radiation effects
Ferritins/biosynthesis
Fibroblasts/enzymology,radiation effects
Heme Oxygenase (Decyclizing)/metabolism
Humans
Lipid Peroxidation/drug effects,radiation effects
Oligonucleotides, Antisense/pharmacology
Oxidation-Reduction
Skin/enzymology,radiation effects
Ultraviolet Rays
Chemicals
Antioxidants
Oligonucleotides, Antisense
Ferritins
Heme Oxygenase (Decyclizing)
Deferoxamine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Vile G F
Swiss Institute for Experimental Cancer Research, ISREC, Lausanne.
Basu-Modak S
Waltner C
Tyrrell R M
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