REGULATION OF CARDIAC FUNCTION BY PKC ISOZYME

PKC 同工酶对心脏功能的调节

• 批准号: 6388456
• 负责人: Nathan Maduka Jideama
• 金额: $ 12.27万
• 依托单位: CLARK ATLANTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-15 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6388456
• 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

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.

Nathan Jideama 博士，美国公民，是一名少数族裔教师，受聘为 克拉克亚特兰大大学助理教授。 Jideama 博士获得 获得亚特兰大大学博士学位并完成博士后 在埃默里大学医学院 J.F. Kuo 博士的指导下接受培训 1996. Jideama 博士的职业目标是发展他的研究，以便 可用于培养少数民族学生。 Jideama博士的研究领域 是通过蛋白激酶和磷酸酶调节心脏功能。 他提出的研究描述如下。 心肌收缩由蛋白激酶（PKC 和 PKA）调节 通过肌原纤维蛋白和蛋白磷酸酶的磷酸化 1 (PP1) 通过这些蛋白质的去磷酸化。 整体 本提案的目的是确定以下各方的协调一致的作用： 蛋白激酶 C (PKC) 同工酶（α、δ、ε 和 zetu）， 蛋白激酶A (PKA) 和蛋白磷酸酶1 (PP1) 的调节 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 将测定 MgATP 酶活性。 位点特异性磷酸化 肌原纤维蛋白的模式将通过两个评估 三维磷酸肽图谱。功能意义 PKC 同工酶和 PKA 磷酸化肌原纤维 PP1 的去磷酸化也将被测定。 心肌细胞 将测量收缩力以确定生化和 磷酸化和去磷酸化的生理效应 心肌原纤维。 预计本研究收集的数据将提供新的 PKC、PKA 和 PPI 调节心脏功能的见解。 它 也将加深我们对心脏功能的了解 收缩装置。