HEME OXYGENASE-1 MEDIATES AN ADAPTIVE RESPONSE TO OXIDATIVE STRESS INHUMAN SKIN FIBROBLASTS

Oxidative stress of human skin fibroblasts by treatment with ultraviol et A (UVA) radiation has been shown to lead to an increase in levels o f the heme catabolizing enzyme heme oxygenase 1 [heme, hydrogen-donor: oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating), EC 1.1 4.99.3] and the iron storage protein ferritin. Here we show that human skin fibroblasts, preirradiated with UVA, sustain less membrane damag e during a subsequent exposure to UVA radiation than cells that had no t been preirradiated. Pretreating cells with heme oxygenase 1 antisens e oligonucleotide inhibited the irradiation-dependent induction of bot h the heme oxygenase 1 enzyme and ferritin and abolished the protectiv e effect of preirradiation. Inhibition of the UVA preirradiation-depen dent increase in ferritin, but not heme oxygenase, with desferrioxamin e also abolished the protection. This identifies heme oxygenase 1 as a crucial enzymatic intermediate in an oxidant stress-inducible antioxi dant defense mechanism, involving ferritin, in human skin fibroblasts.