Mechanisms Of Chemically Induced Photosensitivity

化学诱导光敏性的机制

• 批准号: 7007400
• 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/7007400
• 关键词: DNA damage; Smith Lemli Opitz syndrome; antibacterial agents; apoptosis; carcinogen testing; cytotoxicity; electron spin resonance spectroscopy; environmental exposure; hairless mouse; keratinocyte; mutagen testing; photoactivation; photochemistry; photosensitizing agents; radiation carcinogen; radiation carcinogenesis; radiation hazard; radiobiology; singlet oxygen; tirapazamine; ultraviolet radiation

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

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。 UVA诱导的角质形成细胞中的凋亡与EGF受体内在化和下调有关，而没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照射下产生单线氧和超氧化物，并对角质形成细胞具有光毒性。 A2E是沉积在视网膜中的脂肪霉素颗粒中的脂质降解产物，在年轻的眼睛中具有光保护，但在较老的眼睛中可能具有光毒性。荧光星B，一种用于化妆品的红色染料，作为用于控制果蝇的光毒素，在可见辐射后会产生单线氧和超氧化物，并且对角质形成细胞具有光毒性