title: Susceptibility of skin cells to UVA-induced necrotic cell death reflects the intracellular level of labile iron.
abstract: The mechanism of resistance of keratinocytes to ultraviolet A (UVA) (320-400 nm)-induced oxidative damage has not yet been elucidated. Here, we examined the possible link between the intracellular level of the labile iron pool (LIP) and the susceptibility to UVA-induced cell death using a series of human skin fibroblast and keratinocyte cell lines as a model. Resistance of keratinocytes to UVA-induced cell death was confirmed by flow cytometry and in fibroblasts necrosis was found to be the primary mode of cell death induced by UVA. The percentage of necrosis in fibroblasts also correlated with the extent of intracellular ATP depletion, a hallmark of necrotic cell death. The evaluation of the intracellular level of LIP by calcein assay revealed that both "basal" and "UVA-induced" levels of LIP in keratinocytes were several fold lower than in fibroblasts. Accordingly the dose to give an equivalent level of necrosis was several fold lower in fibroblasts than in keratinocytes. Furthermore, the modulation of "basal" or "UVA-induced" level of LIP by either Desferal and/or hemin treatment significantly affected the extent of UVA-induced necrotic cell death and ATP depletion in all the cell lines. Cellular susceptibility to UVA-induced necrotic cell death appears to reflect the intracellular level of LIP.
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
authors.forename: Julia Li
authors.initials: JL
authors.lastname: Zhong
authors.forename: Anthie
authors.initials: A
authors.lastname: Yiakouvaki
authors.forename: Patricia
authors.initials: P
authors.lastname: Holley
authors.forename: Rex M
authors.initials: RM
authors.lastname: Tyrrell
authors.forename: Charareh
authors.initials: C
authors.lastname: Pourzand
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016923:Cell Death / Q000528:radiation effects*; D002460:Cell Line; D003676:Deferoxamine / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism* / Q000528:radiation effects; D009336:Necrosis; D014466:Ultraviolet Rays
chemical_list: D007502:Iron Chelating Agents; D006427:Hemin; D000255:Adenosine Triphosphate; D007501:Iron; D003676:Deferoxamine