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: 6913699
• 负责人: Jay D Turner
• 金额: $ 2.92万
• 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/6913699
• 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）：由于与酒精的使用和滥用相关的各种有据可查的病理状况，酒精是美国的一个主要公共卫生问题。酒精引起的心脏病是酗酒者大量发病和死亡的原因，然而，对许多潜在分子机制的理解仍然难以捉摸。本研究的目的是检验以下假设：1) 解偶联蛋白 2 (UCP2) 的表达和活性具有直接后果，导致酒精性心肌病 (ACM) 中心肌收缩力下降和心力衰竭的发展，2) 由于氧化损伤过量活性氧 (ROS) 的产生有助于疾病的发生和进展，UCP2 表达的诱导是为了抑制 ROS 的产生并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 产生减少，从而阻碍各种 ATP 依赖性细胞过程，最终导致心肌功能受损和心力衰竭。