CELL/CELL INTERACTIONS IN THROMBOSIS

描述：本更新申请提出了一系列研究， 阐明人脐静脉内皮细胞凋亡的分子基础和调控机制 静脉内皮细胞（HUVEC）外贴。该项目将克隆， 测序、表达HUVEC ADDRESS，并对其进行生物化学表征; 研究结构/功能关系，以确定关键区域 核苷酸结合和酶活性;确定机制 溶血磷脂酰胆碱（lysoPC）、同型半胱氨酸、细胞因子 和生长因子影响酶活性;并评估转录 通过ADDRESS基因的5 '侧翼区的元件调节。 总之，本申请中提出的研究将阐明 人体表面的一种酶 内皮细胞立即代谢ADP， 血小板为此，我们将克隆、测序和表达分离的HUVEC 对其进行生物化学分析和表征;研究结构/功能 确定酶活性关键区域的关系;确定 生物物质如溶血磷脂酰胆碱， 同型半胱氨酸、细胞因子和生长因子影响酶活性;以及 评估5 '-侧翼区元件的转录调节 adjuvant基因。本申请中提出的实验将提供 为今后制定合理有效的 抗血栓治疗，将在最早的阶段， 血栓形成

DESCRIPTION: This renewal application proposes a series of studies to elucidate the molecular basis and regulation of human umbilical vein endothelial cell (HUVEC) ecto-ADPase. The project will clone, sequence and express HUVEC ADPase and characterize it biochemically; study structure/function relationships to identify regions critical for nucleotide binding and enzyme activity; determine the mechanisms by which lysophosphatidylcholine (lysoPC), homocysteine, cytokines and growth factors affect enzyme activity; and assess transcriptional regulation by elements of the 5'-flanking region of the ADPase gene. In summary, research proposed in this application will elucidate molecular mechanisms by which an enzyme on the surface of human endothelial cells immediately metabolizes ADP emerging from activated platelets. To this end we will clone, sequence and express isolated HUVEC ADPase and characterize it biochemically; study structure/function relationships to identify regions critical for enzyme activity; determine mechanisms by which biologic substances such as lysophosphatidylcholine, homocysteine, cytokines and growth factors affect enzyme activity; and assess transcriptional regulation by elements of the 5'-flanking region of the ADPase gene. Experiments proposed in this application will furnish information for future development of rational and effective forms of antithrombotic therapy which will act at the very earliest stages of thrombus formation.