Mechanisms of Chemically Induced Photosensitivity

化学诱导光敏性的机制

• 批准号: 7327795
• 负责人: COLIN CHIGNELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7327795
• 关键词: Mechanisms; Chemically; Induced; Photosensitivity

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

该研究项目的目的是阐明光化学和光生物学机制，即单独或在存在内源或外源光敏剂存在的情况下光（UVA和可见辐射）具有有毒或治疗作用。我们已经表明，UVA在人角质形成细胞中具有致癌潜力，并且PTEN表达降低会导致PI3K/AKT信号的增加，并可能导致凋亡耐药性和恶性转化。我们已经确定皮肤脂质霍利斯塔-5,7,9（11）-trien-3β-OL（9-DDHC）是负责UVA诱导的史密斯 - 莱姆利 - 奥普茨综合征患者皮肤光敏性的推定剂。 9-DDHC在UVA辐照时会产生单线氧和超氧化物，对角质形成细胞具有光毒性，并且在UVA敏感患者的血浆中发现了较高浓度。富勒罗[C60（OH）24]，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