Ultraviolet A radiation induces immediate release of iron in human primaryskin fibroblasts: The role of ferritin

In mammalian cells, the level of the iron-storage protein ferritin (Ft) is tightly controlled by the iron-regulator)? protein-1 (IRP-1) at the posttra nscriptional level. This regulation prevents iron acting as a catalyst in r eactions between reactive oxygen species and biomolecules. The ultraviolet A (UVA) radiation component of sunlight (320-400 nm has been shown to be a source of oxidative stress to skin via generation of reactive oxygen specie s. We report here that the exposure of human primary skin fibroblasts, FEK4 , to UVA radiation causes an immediate release of "free" iron in the cells via proteolysis of Ft. Within minutes of exposure to a range of doses of UV A at natural exposure levels, the binding activity of IRP-1, as well as Ft levels, decreases in a dose-dependent manner. This decrease coincides with a significant leakage of the lysosomal components into the cytosol. Stabili zation of Ft molecules occurs only when cells are pretreated with lysosomal protease inhibitors after UVA treatment. We propose that the oxidative dam age to lysosomes that leads to Ft degradation and the consequent rapid rele ase of potentially harmful "free" iron to the cytosol might be a major fact or in UVA-induced damage to the skin.