Ultraviolet A radiation induces immediate release of iron in human primary skin fibroblasts: the role of ferritin.
In mammalian cells, the level of the iron-storage protein ferritin (Ft) is tightly controlled by the iron-regulatory protein-1 (IRP-1) at the posttranscriptional level. This regulation prevents iron acting as a catalyst in reactions 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 species. 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 UVA 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. Stabilization of Ft molecules occurs only when cells are pretreated with lysosomal protease inhibitors after UVA treatment. We propose that the oxidative damage to lysosomes that leads to Ft degradation and the consequent rapid release of potentially harmful "free" iron to the cytosol might be a major factor in UVA-induced damage to the skin.
Pourzand
C
C
Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom.
Watkin
R D
RD
Brown
J E
JE
Tyrrell
R M
RM
D002478:Cells, Cultured; D005293:Ferritins / Q000378:metabolism*; D005347:Fibroblasts / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011877:Radionuclide Imaging; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays
D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D016601:RNA-Binding Proteins; D005293:Ferritins; D007501:Iron; D035941:Iron Regulatory Protein 1