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

Cardiac Na+/K+-ATPase: Digitalis-Induced Signaling through P13K/Akt Pathway

心脏 Na /K -ATP 酶：洋地黄通过 P13K/Akt 途径诱导的信号传导

基本信息

批准号：
8250440
负责人：
AMIR ASKARI
金额：
$ 29.07万
依托单位：
UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8250440
关键词：
ATP phosphohydrolase Adult Animal Experimentation Animals Attenuated Benign Binding Biochemistry Biological Assay Blood Cardiac Cardiac Glycosides Cardiac Myocytes Cardiovascular Physiology Cavia Cell membrane Cellular biology Communication Complex Data Dependence Digitalis preparation Digoxin Endothelin Endothelin-1 Ensure Enzymes Epidermal Growth Factor Receptor Evaluation Event Funding Genes Goals Growth Heart Heart failure Human Hypertrophy In Vitro Ions Knock-out Knowledge Lead Membrane Mitochondria Modeling Molecular Molecular Genetics Mus Muscle Cells Myocardial Ischemia Na(+)-K(+)-Exchanging ATPase Neonatal Ouabain Pathway interactions Pharmaceutical Preparations Pharmacology Phosphotransferases Physiological Potassium Channel Prevention approach Principal Investigator Program Research Project Grants Proline-Rich Domain Protein Biosynthesis Protein Chemistry Protein Isoforms Proteins Rattus Recruitment Activity Regimen Regulation Reperfusion Injury Research Research Personnel Resource Sharing Role SH3 Domains Signal Pathway Signal Transduction Signal Transduction Pathway Testing Transcriptional Regulation Transducers Transgenic Mice Transgenic Organisms Wild Type Mouse Work base cell type constriction design man novel strategies pressure programs receptor research study synthetic peptide

项目摘要

This application is the resubmission for the competing continuation of a program project grant that was initiated in 1986. The proposed research is the outgrowth of the program's progress during the current funding period, and consists of three projects and two supporting cores, focused on the central theme of digitalis-induced signaling through the cardiac Na*7K+-ATPase. The participating investigators with expertise in membrane biochemistry, protein chemistry, molecular genetics, cell biology, and integrative cardiovascular physiology/ pharmacology will combine their efforts to conduct the following studies: Project I attempts to determine the molecular and cellular mechanisms by which the digitalis-induced activation of class 1A PI3K/Akt pathway leads to cardiac myocyte hypertrophy, and to assess if this seemingly benign hypertrophy is capable of antagonizing the deleterious effects of pathological hypertrophy and its consequences. Project 11 concentrates on the unraveling of the molecular interactions that constitute the formation of the Na+/K+- ATPase/Src complex, and on the evaluation of this complex as the receptor for the initiation of the multiple digitalis-induced signaling pathways and their functional consequences in the heart. Project III focuses on the established digitalis-induced communication between cardiac sarcolemmal Na+/K+-ATPase and ATPsensitive K+ channels of cardiac mitochondria, and proposes to determine the molecular and subcellular mechanisms of this communication, and the resulting digitalis-induced protection of the heart against ischemia-reperfusion injury. The core units are designed to provide administrative support and efficient management of the experimental animals and other shared resources of the program. These proposed studies are expected to expand knowledge on the newly appreciated physiological roles of cardiac NaVK4- ATPase, and to provide the bases for novel approaches to the prevention and treatment of ischemic heart disease and heart failure.

本申请是对计划项目拨款的竞争性延续的重新提交