title: Heme oxygenase activity causes transient hypersensitivity to oxidative ultraviolet A radiation that depends on release of iron from heme.
abstract: Heme oxygenase (HO) breaks down heme to iron, biliverdin, and carbon monoxide, and activity of this enzyme increases in many tissues and cell types after exposure to oxidative stress. There is evidence that increased HO activity is involved in long-term protective mechanisms against oxidative stress. We studied the effect of artificially overexpressed HO activity on the cytotoxicity of oxidative ultraviolet A (UVA) radiation after loading human cells with the HO substrate ferric heme (hemin). In contrast to the reported long-term protection attributed to HO activity, cells overexpressing HO activity were hypersensitive to UVA radiation shortly after heme treatment when compared with control cells. Cells overexpressing HO activity showed an increased rate of heme consumption and a higher level of accumulated free chelatable iron when compared with control cells. The hypersensitivity of cells overexpressing HO to UVA radiation after heme treatment was apparently caused by the increased accumulation of chelatable iron, because the iron chelator desferrioxamine strongly reduced the hypersensitivity. One day after the heme treatment, cells overexpressing HO activity were no longer hypersensitive to UVA radiation. We conclude that increased HO activity can temporarily increase the sensitivity of cells to oxidative stress by releasing iron from heme.
authors.affiliation: The Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Kvam
authors.forename: V
authors.initials: V
authors.lastname: Hejmadi
authors.forename: S
authors.initials: S
authors.lastname: Ryter
authors.forename: C
authors.initials: C
authors.lastname: Pourzand
authors.forename: R M
authors.initials: RM
authors.lastname: Tyrrell
mesh_terms: D002470:Cell Survival; D003676:Deferoxamine / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006418:Heme / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006427:Hemin / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000502:physiology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010777:Photochemistry; D011836:Radiation Tolerance / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014466:Ultraviolet Rays
chemical_list: D007502:Iron Chelating Agents; D011993:Recombinant Fusion Proteins; D006418:Heme; D006427:Hemin; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D003676:Deferoxamine