POLY RIBOSE SYNTHETASE & ENDOTHELIAL DYSFUNCTION IN IDDM

描述（改编自申请人摘要）：在多种细胞类型中 （包括血管内皮细胞和血管平滑肌细胞）， 暴露于细胞毒性氧化剂，如过氧亚硝酸盐，导致细胞 能量衰竭当DNA链断裂时，核酶poly（ADP） 核糖合成酶（PARS）启动一种能量消耗，效率低下的修复 循环，其中NAD的ADP核糖基部分转移到蛋白质受体。的 二核苷酸池的最终耗尽涉及细胞的生长过程， 死亡在动物和细胞培养模型中，PARS的保护作用 抑制或缺乏PARS基因。因此，调查人员 建议定义PARS在内皮细胞发育过程中的作用， 糖尿病相关高血糖症体外模型中的损伤。两个具体 目的是：（1）确定是否抑制或遗传失活 PARS影响高血压诱导的内皮功能障碍的发展， 葡萄糖条件下;（2）研究高血糖的机制 葡萄糖诱导的内皮细胞死亡和PARS在此过程中的作用。

DESCRIPTION (adapted from the applicant's abstract): In a variety of cell types (including vascular endothelial cells and vascular smooth muscle cells), exposure to cytotoxic oxidants such as peroxynitrite, results in cellular energetic failure. Upon DNA strand breakage, the nuclear enzyme poly (ADP) ribose synthetase (PARS) initiates an energy consuming, inefficient repair cycle, with transfer of the ADP ribosyl moiety of NAD to protein acceptors. The resultant depletion of dinucleotide pools is implicated in the process of cell death. In animal and cell culture models, a protective effect of PARS inhibition or lack of PARS gene has been demonstrated. Thus, the investigators propose to define the role of PARS in the process of development of endothelial injury in an in vitro model of diabetes-associated hyperglycemia. Two specific aims are proposed: (1) to establish whether inhibition or genetic inactivation of PARS affects the development of endothelial dysfunction induced by high glucose conditions; and (2) to investigate the mechanism of high glucose-induced endothelial cell death and the role of PARS in the process.