Ultraviolet Light Induced Phenomena in Biomembranes

EXCEEDTHE空格键。 紫外线辐射(UVR)对人体皮肤有多种有害和有益的影响。单次曝光 正常皮肤对紫外线照射会引发炎症、黑色素生成、维生素D生成，并可能 造成免疫抑制。长期暴露在太阳紫外线照射下会导致非黑色素瘤皮肤癌，影响 黑色素瘤的发展，并导致皮肤光老化。UVR还被用于治疗皮肤病，最引人注目的是 银屑病。最近的研究表明，细胞对UVR的反应，如生存反应和凋亡 包括质膜内及其附近的早期信号事件。这些反应在长时间后被观察到 波长UVA辐射以及较短波长的UVB辐射，以前被认为是 只以核DNA为目标。这项研究的长期目标是了解分子 太阳紫外线照射引起皮肤变化的机制，以防止不良影响和发展紫外线照射。 皮肤病的基础疗法。这项拟议的研究旨在提供对 主要的光化学，重点是发生在质膜上的事件，关于紫外线诱导的 皮肤细胞的新基因表达、细胞凋亡和炎性介质的产生。 将在人类角质形成细胞和成纤维细胞中进行研究，以完成这些特定的臂：1) 验证质膜上的UVR光化学可以启动早期信号事件的假设 可能介导基因表达和细胞凋亡的质膜。体内和附近的内源生色团 质膜将使用逝去波辐射选择性地激发；反应氧化物种(ROS)， 将评估膜受体的聚集、基因表达的诱导和细胞凋亡。2)评估 特定的ROS在以下情况下启动信号事件从而诱导基因表达和细胞凋亡的能力 在质膜或特定的亚细胞位置产生。3)来检验这样的假设 7-脱氢胆固醇(7-DHC)的膜含量改变了UVA诱导的炎症介质的产生。 人角质形成细胞和成纤维细胞将补充7-DHC和UVA诱导的PGE2的产生 并测定IL-LCC。

EXCEEDTHE SPACEPROVIDED. Ultraviolet radiation (UVR) has multiple deleterious and beneficial effects on human skin. Single exposures of normal skin to solar UVR elicit inflammation,melanogenesis, vitamin D production, and may cause immune suppression. Chronic exposure to solar UVR produces non-melanoma skin cancer, influences development of melanoma and leads to skin photoaging. UVR is also used to treat skin diseases, most notably psoriasis. Recent work has demonstrated that cell responses to UVR such as survival responses and apoptosis involve early signaling events in and near the plasma membrane. These responses are observed after long wavelength UVA radiation as well as shorter wavelength UVB radiation, which had previously been thought to target nuclear DNA exclusively. The long-range objectives of this research are to understand the molecular mechanisms for solar UVR-induced alterations in skin in order to prevent adverse effects and to develop UVR- based therapies for skin diseases. The proposed research is designed to provide fundamental understanding of the the primary photochemistry, with emphasis on the events occurring at the plasma membrane, on UVR induced new gene expression, apoptosis and generation of inflammatory mediators in skin cells. Studies in human keratinocytes and fibroblasts will be carried out to accomplish these specific arms: 1)To test the hypothesis that UVR photochemistry at the plasma membrane can initiate early signaling events in the plasma membrane that may mediate gene expression and apoptosis. Endogenous chromophores in and near the plasma membrane will be selectively excited using evanescent wave radiation; reactive oxidizing species (ROS), clustering of membrane receptors, induction of gene expression and apoptosis will be assessed. 2) To evaluate the ability of specific ROS to initiate signaling events leading to induction of gene expression and apoptosis when created either at the plasma membrane or specific subcellular locations. 3) To test the hypothesis that the plasma membrane content of 7-dehydrocholesterol (7-DHC) alters UVA-induced production of inflammatory mediators. Human keratinocytes and fibroblasts will be supplemented with 7-DHC, and UVA-induced production of PGE2 and IL-lcc will measured.