Photooxidation Generates Biologically Active Phospholipids That Induce Heme Oxygenase-1 in Skin Cells
| Autor: | Alexandra Kadl, Erwin Tschachler, Florian Gruber, Michael Mildner, Bernd R. Binder, Barbara Lengauer, Paul Mrass, Gerhard Krönke, Alexander Leitner, Veronika Mlitz, Valery N. Bochkov, Norbert Leitinger, Olga Oskolkova |
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| Rok vydání: | 2007 |
| Předmět: |
Keratinocytes
Ultraviolet Rays Phospholipid Biochemistry Epitopes chemistry.chemical_compound Lipid oxidation Humans Enzyme inducer Molecular Biology Heme Cells Cultured Phospholipids DNA Primers chemistry.chemical_classification Biliverdin Base Sequence Singlet Oxygen biology Chemistry Biological activity Cell Biology Heme oxygenase Enzyme Enzyme Induction Heme Oxygenase (Decyclizing) biology.protein Chromatography Thin Layer sense organs Oxidation-Reduction |
| Zdroj: | Journal of Biological Chemistry. 282:16934-16941 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m702523200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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