Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin

GF Vile, RM Tyrrell - Journal of Biological Chemistry, 1993 - Elsevier
Journal of Biological Chemistry, 1993Elsevier
Heme oxygenase-1 mRNA levels increase following exposure of many mammalian cell
lines to oxidative stress such as ultraviolet A (UVA) irradiation. Here we demonstrate a 4-fold
increase in microsomal heme oxygenase activity and a 40% decrease in microsomal heme
content 14 h after treatment of human skin fibroblasts (FEK4) with 250 kJ m-2 of UVA
radiation. Paralleling this was a 2-fold increase in ferritin levels that was sustained for at
least 46 h after UVA irradiation. Treatment of fibroblasts with the iron chelating agent …
Heme oxygenase-1 mRNA levels increase following exposure of many mammalian cell lines to oxidative stress such as ultraviolet A (UVA) irradiation. Here we demonstrate a 4-fold increase in microsomal heme oxygenase activity and a 40% decrease in microsomal heme content 14 h after treatment of human skin fibroblasts (FEK4) with 250 kJ m-2 of UVA radiation. Paralleling this was a 2-fold increase in ferritin levels that was sustained for at least 46 h after UVA irradiation. Treatment of fibroblasts with the iron chelating agent desferrioxamine, after the UVA-dependent induction of heme oxygenase, prevented the increase in ferritin levels. Treatment of fibroblasts with Sn-protoporphyrin IX (an inhibitor of heme oxygenase) also prevented the effect of UVA radiation on ferritin levels. Thus we conclude that the effect of UVA radiation on ferritin levels is via the heme oxygenase-dependent release of iron from endogenous heme sources. We propose that the increase in ferritin that follows UVA irradiation would decrease intracellular free iron such that iron-catalyzed free radical reactions would be restricted during periods of subsequent oxidative stress.
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