Mechanisms Of Chemically Induced Photosensitivity

本研究项目的目的是阐明光（UVA和可见光辐射）单独或在内源性或外源性光敏剂存在下产生毒性或治疗作用的光化学和光生物学机制。UVA诱导的角质形成细胞凋亡与EGF受体内化和下调有关，而不伴有受体磷酸化和泛素化; UVA暴露也会导致ERK MAP激酶的延迟和持续激活。我们已经确定皮肤脂质胆甾-5，7，9（11）-三烯-3 β-醇（9-DDHC）是Smith-Lemli-Opitz综合征患者UVA诱导皮肤光敏性的假定因子。9-DDHC在UVA照射后产生单线态氧和超氧化物，并且对角质形成细胞具有光毒性。A2 E是沉积在视网膜中的脂褐质颗粒中发现的脂质降解产物，在年轻的眼睛中具有光保护作用，但在老年眼睛中可能具有光毒性。荧光桃红B是一种用于化妆品的红色染料，也是控制果蝇的光毒素，在可见光照射下产生单线态氧和超氧化物，对角质形成细胞具有光毒性

The objective of this research project is to elucidate the photochemical and photobiological mechanisms whereby light (UVA and visible radiation) alone or in the presence of endogenous or exogenous photosensitizers exerts either toxic or therapeutic effects. UVA-induced apoptosis in keratinocytes is associated with EGF receptor internalization and down-regulation without receptor phosphorylation and ubiquitination; also UVA exposure causes delayed and sustained activation of ERK MAP kinase. We have identified the skin lipid cholesta-5,7,9(11)-trien-3 beta-ol (9-DDHC) as the putative agent responsible for UVA-induced skin photosensitivity in Smith-Lemli-Opitz syndrome patients. 9-DDHC generates singlet oxygen and superoxide upon UVA irradiation and is phototoxic to keratinocytes. A2E, a lipid degradation product found in lipofuscin granules deposited in the retina, is photoprotective in the young eye but may be phototoxic in older eyes. Phloxine B, a red dye used in cosmetics and as a phototoxin for the control of fruit flies, generates singlet oxygen and superoxide upon visible irradiation and is phototoxic to keratinocytes