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Ultraviolet Light Induced Phenomena in Biomembranes

生物膜中的紫外线诱导现象

基本信息

批准号：
7176379
负责人：
IRENE KOCHEVAR
金额：
$ 10.79万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1981
资助国家：
美国
起止时间：
1981-09-01 至 2007-02-28
项目状态：
已结题

项目摘要

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.

超出提供的空间。紫外线辐射（UVR）对人体皮肤有多种有害和有益的影响。单次曝光正常皮肤接触太阳紫外线会引发炎症、黑色素生成、维生素 D 生成，并可能造成免疫抑制。长期暴露于太阳紫外线会产生非黑色素瘤皮肤癌，影响黑色素瘤的发展并导致皮肤光老化。紫外线还用于治疗皮肤病，尤其是银屑病。最近的研究表明，细胞对 UVR 的反应，例如生存反应和细胞凋亡涉及质膜内和附近的早期信号事件。这些反应是在长时间后观察到的波长 UVA 辐射以及较短波长的 UVB 辐射，此前人们认为这些辐射专门针对核DNA。这项研究的长期目标是了解分子太阳紫外线引起的皮肤改变的机制，以防止不良影响并发展紫外线- 皮肤病的基础疗法。拟议的研究旨在提供对主要光化学，重点是质膜上发生的事件，UVR 诱导的皮肤细胞中新基因的表达、细胞凋亡和炎症介质的产生。将进行人类角质形成细胞和成纤维细胞的研究来完成这些特定的任务：1) 检验质膜上的 UVR 光化学可以启动细胞中早期信号事件的假设质膜可能介导基因表达和细胞凋亡。内源性发色团及其附近使用倏逝波辐射选择性地激发质膜；活性氧化物质（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 ROS 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）检验等离子体的假设 7-脱氢胆固醇 (7-DHC) 的膜含量会改变 UVA 诱导的炎症介质的产生。人类角质形成细胞和成纤维细胞将补充 7-DHC 和 UVA 诱导的 PGE2 产生并测量 IL-lcc。