Photooxidation generates biologically active phospholipids that induce heme oxygenase-1 in skin cells
Photooxidation generates biologically active phospholipids that induce heme oxygenase-1 in skin cells
复制标题
DOI：
10.1074/jbc.m702523200
复制
发表时间：
2007-06-08
影响因子：
4.8
通讯作者：
Tschachler, Erwin
中科院分区：
文献类型：
--
作者：
Gruber, Florian;Oskolkova, Olga;Tschachler, Erwin
血红素氧合酶-1（HO-1）是细胞对组织损伤和氧化应激反应的关键酶。HO-1酶活性导致细胞保护代谢物CO和胆绿素的形成。在皮肤中，长波紫外线辐射（UVA-1）后强烈诱导HO-1。在这里，我们表明，UVA-1照射产生氧化磷脂衍生自1-棕榈酰-2-花生四烯酸-sn-甘油-3-磷酸胆碱（PAPC）介导的HO-1在皮肤细胞中的表达。使用识别氧化磷脂的EO 6抗体，我们发现UVA-1照射皮肤成纤维细胞产生氧化特异性表位。辐射的花生四烯酸磷脂与UVA-1导致形成定义的脂质氧化产物，包括环氧异前列腺素-磷脂酰胆碱诱导HO-1表达在真皮成纤维细胞，角质形成细胞，并在三维表皮等效模型。此外，我们还证明了UVA-1对PAPC的氧化是一种单重态氧依赖性机制。总之，我们提出了一种新的机制，UVA-1诱导HO-1的表达，介导的生物活性磷脂氧化产物的产生。由于UVA-1照射是几种炎症性皮肤病的主要治疗方法，因此UVA-1产生的具有HO-1诱导能力的生物分子的结构鉴定应该导致可以替代照射的药物的开发。
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 arachidonatecontaining 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.