REGULATION OF CARDIAC FUNCTION BY PKC ISOZYME

PKC 同工酶对心脏功能的调节

基本信息

批准号：
6536520
负责人：
Nathan Maduka Jideama
金额：
$ 12.37万
依托单位：
CLARK ATLANTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-07-15 至 2004-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6536520
关键词：
adenosinetriphosphatase cardiac myocytes heart contraction heart function isozymes laboratory rat myofibrils phosphoprotein phosphatase phosphorylation protein kinase A protein kinase C protein structure function tissue /cell culture

项目摘要

Dr. Nathan Jideama, citizen of the US is a minority faculty employed as an assistant professor at Clark Atlanta University. Dr. Jideama earned a Ph.D degree from Atlanta University and completed post doctoral training under Dr. J.F. Kuo at Emory University School of Medicine in 1996. Dr. Jideama's career goal is to develop his research such that it can be used to train minority student. Dr. Jideama's research area is regulation of cardiac functions by protein kinases and phosphotases. His proposed research is described below. Cardiac muscle contraction is regulated by protein kinases (PKC and PKA) through phosphorylation of myofibrillar proteins and protein phosphotase 1 (PP1) through dephosphorylation of these proteins. The overall objective of this proposal is to determine the concerted roles of protein kinase C (PKC) isozymes (alpha,,delta,,epsilon, and zetu), protein kinase A (PKA) and protein phosphatase 1 (PP1) in the regulation of cardiac functions. Phosphorylation, dephosphorylation, activity assay and contractile measurements of myocytes will be used to determine the roles of PKC isozymes, PKA and PP1 in cardiac functions. The effects of phosphorylation and dephosphorylation on Ca2+--stimulated MgATPase activity will be determined. Site-specific phosphorylation patterns of myofibrillar proteins will be evaluated through two- dimensional phosphopeptide mapping. Functional significance of phosphorylation of myofibrils by PKC isozymes and PKA and the dephosphorylation by PP1 will also be determined. Cardiomyocytes contractility will be measured to determine the biochemical and physiological effects of phosphorylation and dephosphorylation of cardiac myofibrils. It is anticipated that data collected from this study will provide new insights in the regulation of heart function by PKC, PKA and PPI. It will also enhance our understanding of the functions of cardiac contractile apparatus.

美国公民Nathan Jideama博士是少数派教职员工克拉克亚特兰大大学的助理教授。 Jideama博士赢得了来自亚特兰大大学的博士学位并完成了博士后博士学位埃默里大学医学院的J.F. Kuo博士的培训 1996。Jideama博士的职业目标是发展他的研究它可用于培训少数族裔学生。 Jideama博士的研究领域是蛋白激酶和磷酸酶对心脏功能的调节。他提出的研究如下所述。心肌收缩受蛋白激酶（PKC和PKA）调节通过肌原纤维蛋白和蛋白质磷酸酶的磷酸化 1（PP1）通过这些蛋白质的去磷酸化。总体该提议的目的是确定蛋白激酶C（PKC）同工酶（alpha，delta，epsilon和Zetu），调节中的蛋白激酶A（PKA）和蛋白质磷酸酶1（PP1）心脏功能。磷酸化，去磷酸化，活性肌细胞的测定和收缩测量将用于确定 PKC同工酶，PKA和PP1在心脏功能中的作用。这磷酸化和去磷酸化对Ca2+刺激的影响将确定MGATPase活性。位点特异性磷酸化肌原纤维蛋白的模式将通过两种尺寸磷酸肽映射。功能意义 PKC同工酶和PKA和PKA磷酸化以及 PP1的去磷酸化也将得到确定。心肌细胞将测量收缩性以确定生化和磷酸化和去磷酸化的生理影响心脏肌原纤维。预计从这项研究收集的数据将提供新的 PKC，PKA和PPI对心脏功能调节的见解。它还将增强我们对心脏功能的理解收缩设备。