权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

POLY (ADP-RIBOSE) SYNTHETASE AND REPERFUSION INJURY

聚（ADP-核糖）合成酶和再灌注损伤

基本信息

批准号：
2857941
负责人：
CSABA SZABO
金额：
$ 20.31万
依托单位：
INOTEK PHARMACEUTICALS CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-01-01 至 2000-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2857941
关键词：
DNA damage bioenergetics cellular pathology enzyme activity enzyme deficiency enzyme inhibitors gene targeting hydroxyl radical laboratory mouse laboratory rabbit laboratory rat myocardial infarct sizing myocardial ischemia /hypoxia pentosyltransferase peroxynitrites reperfusion vascular endothelium

项目摘要

DESCRIPTION (adapted from the applicant's abstract): The current proposal is aimed at investigating the role of the nuclear enzyme poly (ADP-ribose) synthetase (PARS) in the pathophysiology of myocardial ischemia-reperfusion injury. First, it will be established whether pharmacological inhibition of PARS ameliorates the cellular energetic derangement and the functional alterations during myocardial ischemia-reperfusion injury. This hypothesis will be tested in in vitro perfused heart preparations and in a mouse model of myocardial ischemia-reperfusion injury by correlating DNA strand-breakage, PARS activity, intracellular energetics, and myocardial contractility. PARS will be inhibited by pharmacological and molecular biological approaches. For the pharmacological approach, 3-aminobenzamide, a prototypical inhibitor of PARS will be used. Moreover, responses will be compared in hearts of wild-type mice and of knock-out mice lacking the functional PARS enzyme. The relative contribution of hydroxyl radical versus peroxynitrite in the activation of PARS in myocardial ischemia-reperfusion will also be addressed using pharmacological inhibitors. The principal investigator will also investigate the changes in endothelial function during myocardial reperfusion injury, and the role of PARS in these changes.

描述（改编自申请人摘要）：当前提案目的是研究核酶聚（ADP-核糖） PARS在心肌缺血再灌注病理生理中的作用损伤首先，将确定是否有药理学抑制 PARS改善细胞能量紊乱和功能性心肌缺血-再灌注损伤过程中的变化。这一假设将在体外灌注心脏制备物和小鼠模型中进行测试心肌缺血-再灌注损伤相关DNA 链断裂、PARS活性、细胞内能量学和心肌收缩性 PARS将被药理学和分子生物学抑制，生物学方法。对于药理学方法，3-氨基苯甲酰胺，将使用PARS的原型抑制剂。此外，应对措施将是在野生型小鼠和缺乏该基因的基因敲除小鼠的心脏中进行比较，功能性PARS酶羟基自由基的相对贡献与过氧亚硝酸盐在心肌PARS激活中的作用缺血-再灌注也将使用药理学方法来解决。抑制剂的主要研究者还将调查内皮功能在心肌再灌注损伤中的作用在这些变化中。