Mechanisms of Chemically Induced Photosensitivity

本研究项目的目的是阐明光（UVA和可见光）单独或在内源性或外源性光敏剂的存在下产生毒性或治疗作用的光化学和光生物学机制。我们已经证明UVA在人角质形成细胞中具有致癌潜力，PTEN表达的降低导致PI3K/AKT信号的增加，并可能促进凋亡抵抗和恶性转化。我们已经确定皮肤脂质胆固醇-5,7,9(11)-三烯-3 - β -醇（9- ddhc）可能是uva诱导的Smith-Lemli-Opitz综合征患者皮肤光敏的原因。9-DDHC在UVA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，在UVA敏感患者的血浆中发现浓度较高。富勒醇[C60(OH)24]是一种水溶性富勒烯，对人视网膜色素上皮（hRPE）细胞具有细胞毒性和光毒性

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. We have shown that UVA has carcinogenic potential in human keratinocytes and that the decreased PTEN expression resulted in increased PI3K/AKT signaling and may contribute to apoptotic resistance and malignant transformation. 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, is phototoxic to keratinocytes and is found in higher concentrations in plasma from UVA sensitive patients. Fullerol [C60(OH)24], a water soluble fullerene, is cytotoxic and phototoxic to human retinal pigment epithelial (hRPE) cells