Role of uncoupling protein-2 in alcoholic cardiomyopathy

解偶联蛋白2在酒精性心肌病中的作用

• 批准号: 7083567
• 负责人: Jay D Turner
• 金额: $ 4.03万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7083567
• 关键词: adenosine triphosphate; alcoholism /alcohol abuse; beta adrenergic receptor; calcium flux; cardiac myocytes; electron transport; free radical oxygen; gene expression; genetically modified animals; heart contraction; immunocytochemistry; laboratory mouse; laboratory rat; membrane transport proteins; mitochondrial membrane; myocardium disorder; oxidation reduction reaction; oxidative stress; predoctoral investigator; sarcoplasmic reticulum; tocopherols; western blottings

DESCRIPTION (provided by applicant): Alcohol is a major public health concern in the United States due to the various well-documented pathological conditions associated with its use and abuse. Alcohol-induced heart disease is responsible for significant amount of morbidity and mortality in alcoholics, however, the understanding of many of the underlying molecular mechanisms remains elusive. The goal of this study is to test the hypotheses that 1) uncoupling protein-2 (UCP2) expression and activity has direct consequences which contribute to decreased myocardial contractility and the development of heart failure in alcoholic cardiomyopathy (ACM), 2) oxidative damage due to generation of excess reactive oxygen species (ROS) contributes to disease onset and progression, and UCP2 expression is induced in an effort to dampen ROS generation and to prevent further oxidative damage, and 3) this adaptive change leading to UCP2 expression leads to decreased ATP production, thus hindering various ATP-dependent cellular processes and ultimately contributing to compromised myocardial function and heart failure.

描述（由申请人提供）：由于与使用和滥用相关的各种有据可查的病理状况，酒精是美国的主要公共卫生问题。酒精引起的心脏病是酗酒者的大量发病率和死亡率的原因，但是，对许多基本分子机制的理解仍然难以捉摸。这项研究的目的是测试假设，即1）解开蛋白-2（UCP2）表达和活性具有直接的后果，导致心肌收缩力降低以及酒精性心肌病（ACM）的心力衰竭的发展，2）氧化性损害，导致过量的反应性氧气（ROS）的发挥作用和势力的疾病构成势力和UC 2的疾病，UC2的努力和UC2的努力构成了2，UC2的努力是UC的2.防止进一步的氧化损伤，3）这种适应性变化导致UCP2表达导致ATP产生降低，从而阻碍了各种ATP依赖性细胞过程，并最终导致了损害心肌功能和心力衰竭。