title: Contrasting effects of excess ferritin expression on the iron-mediated oxidative stress induced by tert-butyl hydroperoxide or ultraviolet-A in human fibroblasts and keratinocytes.
abstract: Iron and/or ferritin accumulation are known to occur under pathological conditions in many inflammatory skin diseases or in human skin chronically exposed to UV light. Under such conditions, ferritin is believed to play an effective protective role in accommodating and 'deactivating' excess 'free' iron produced by the inflammatory process or the UV illumination. The present study compares the relationship between ferritin over-expression and effects of an oxidative stress induced chemically by tert-butyl hydroperoxide or photochemically by UV-A radiation. As shown by immunoassay, cultured MRC 5 and HS 68 fibroblasts treated for at least one day with transferrin or overnight with non-toxic concentrations of the ferric nitrilotriacetate complex express up to 10 times more ferritin than untreated cells, whereas a five-fold increase is obtained with NCTC 2544 keratinocytes. In all cases a parallel increase in soluble cellular iron is measured by inductive plasma emission spectroscopy. The superoxide dismutase and catalase activities and total glutathione levels are not modified by the iron treatment, whereas a transient increase in the Se-dependent glutathione peroxidase activity of keratinocytes is observed after a short incubation with the iron complex. In keratinocytes and fibroblasts, ferritin over-expression after iron treatment markedly inhibits lipid peroxidation but, paradoxically, not the mortality induced by tert-butyl hydroperoxide. In contrast, this excess ferritin does not protect cells from both the peroxidation and mortality induced by moderate doses (30 J/cm2) of UV-A radiation. As a consequence, protection against oxidative damage by excess ferritin synthesis clearly depends on the nature of the oxidative stress on cell targets and it seems to be of lesser importance in the case of photochemically induced oxidation.
authors.affiliation: Laboratoire de Photobiologie, INSERM U.312, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Giordani
authors.forename: J
authors.initials: J
authors.lastname: Haigle
authors.forename: P
authors.initials: P
authors.lastname: Leflon
authors.forename: A
authors.initials: A
authors.lastname: Risler
authors.forename: S
authors.initials: S
authors.lastname: Salmon
authors.forename: M
authors.initials: M
authors.lastname: Aubailly
authors.forename: J C
authors.initials: JC
authors.lastname: Mazière
authors.forename: R
authors.initials: R
authors.lastname: Santus
authors.forename: P
authors.initials: P
authors.lastname: Morlière
mesh_terms: D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005290:Ferric Compounds / Q000494:pharmacology*; D005293:Ferritins / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D008168:Lung; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014466:Ultraviolet Rays; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
chemical_list: D005290:Ferric Compounds; D017392:Thiobarbituric Acid Reactive Substances; D005293:Ferritins; D020122:tert-Butylhydroperoxide; D007501:Iron; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate