CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY

缺铜时的心脏特征

• 批准号: 6183751
• 负责人: DENIS M MEDEIROS
• 金额: $ 10.07万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183751
• 关键词: adenosinetriphosphatase; cell component structure /function; copper; cytochrome oxidase; disease /disorder etiology; gel mobility shift assay; gene expression; heart enlargement; laboratory rat; malnutrition; metal metabolism disorder; mitochondria; muscle hypertrophy; northern blottings; nutrition related tag; pathologic process; transcription factor; western blottings

DESCRIPTION: This revised application proposes to study the hypothesis that the impact of copper (Cu) deficiency on the heart acts as if it is due to a mitochondrial genetic disease which influences mitochondrial biogenesis, and that this effect is mediated by up-regulation of transcriptional factors which are responsible for the pathology and biochemistry. These changes include decreases in cytochrome c oxidase (CCO) activity and absolute amounts of the nuclear--encoded peptide subunits. In addition, the delta subunit of ATP synthase is markedly decreased and the e subunit of ATPase is significantly increased. These changes would induce the mitochondrial biogenesis and subsequent increase in cardiac mass that is observed in the hearts from copper-deficient rats. This proposal thus will examine three specific aims: 1. To determine if the expression and DNA binding activity of several transcriptional factors, know to regulate nuclear and mitochondrial encoded genes, are increased in hearts from copper deficient rats. 2. To determine if the gene regulatory program involved in mitochondrial biogenesis in copper deficiency is similar to the pressure-overload induced model of myocyte hypertrophy and 3. To determine if the functional properties of ATP synthase and inhibitory ATP synthase protein are decreased in hearts from copper-deficient rats.

描述：此修订申请旨在研究假设

项目成果

Mitochondrial transcription factor A is increased but expression of ATP synthase beta subunit and medium-chain acyl-CoA dehydrogenase genes are decreased in hearts of copper-deficient rats.

在缺铜大鼠的心脏中，线粒体转录因子 A 增加，但 ATP 合成酶 β 亚基和中链酰基辅酶 A 脱氢酶基因的表达减少。

• DOI: 10.1093/jn/130.9.2143
• 发表时间: 2000
• 期刊: The Journal of nutrition
• 作者: Mao,S;Leone,TC;Kelly,DP;Medeiros,DM
• 通讯作者: Medeiros,DM