title: Photooxidation generates biologically active phospholipids that induce heme oxygenase-1 in skin cells.
abstract: Heme oxygenase-1 (HO-1) is a key enzyme in the cellular response to tissue injury and oxidative stress. HO-1 enzymatic activity results in the formation of the cytoprotective metabolites CO and biliverdin. In the skin, HO-1 is strongly induced after long wave ultraviolet radiation (UVA-1). Here we show that UVA-1 irradiation generates oxidized phospholipids derived from 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC) that mediate the expression of HO-1 in skin cells. Using EO6 antibodies that recognize oxidized phospholipids, we show that UVA-1 irradiation of dermal fibroblasts generates oxidation-specific epitopes. Irradiation of arachidonate-containing phospholipids with UVA-1 led to formation of defined lipid oxidation products including epoxyisoprostane-phosphatidylcholine that induced HO-1 expression in dermal fibroblasts, in keratinocytes, and in a three-dimensional epidermal equivalent model. In addition, we demonstrate that the oxidation of PAPC by UVA-1 is a singlet oxygen-dependent mechanism. Together, we present a novel mechanism of UVA-1-induced HO-1 expression that is mediated by the generation of biologically active phospholipid oxidation products. Because UVA-1 irradiation is a mainstay treatment of several inflammatory skin diseases, structural identification of UVA-1-generated biomolecules with HO-1-inducing capacity should lead to the development of drugs that could substitute for irradiation.
authors: Deparment of Dermatology, Medical University of Vienna, Vienna 1090, Austria.
authors: Florian
authors: F
authors: Gruber
authors: Olga
authors: O
authors: Oskolkova
authors: Alexander
authors: A
authors: Leitner
authors: Michael
authors: M
authors: Mildner
authors: Veronika
authors: V
authors: Mlitz
authors: Barbara
authors: B
authors: Lengauer
authors: Alexandra
authors: A
authors: Kadl
authors: Paul
authors: P
authors: Mrass
authors: Gerhard
authors: G
authors: Krönke
authors: Bernd R
authors: BR
authors: Binder
authors: Valery N
authors: VN
authors: Bochkov
authors: Norbert
authors: N
authors: Leitinger
authors: Erwin
authors: E
authors: Tschachler
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D017931:DNA Primers; D004790:Enzyme Induction; D000939:Epitopes / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000528:radiation effects*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000276:immunology / Q000378:metabolism*; D026082:Singlet Oxygen; D014466:Ultraviolet Rays
chemical_list: D017931:DNA Primers; D000939:Epitopes; D010743:Phospholipids; D026082:Singlet Oxygen; D006419:Heme Oxygenase (Decyclizing)