CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY

描述：此修订后的申请建议研究假设 铜（Cu）缺乏对心脏的影响就好像它是 由于线粒体遗传疾病， 生物发生，这种作用是通过上调 转录因子是负责病理和 生物化学这些变化包括细胞色素c氧化酶的减少 (CCO)核编码肽的活性和绝对量 亚单位。此外，ATP合酶的δ亚基显著地 ATP酶的E亚基显著增加。这些 这些变化将诱导线粒体的生物合成， 在缺铜大鼠的心脏中观察到的心脏质量。 因此，本提案将审查三个具体目标：1.以确定是否 几种转录因子的表达和DNA结合活性 已知调节核和线粒体编码基因的因子， 铜缺乏大鼠的心脏中增加。2.以确定是否 基因调控程序参与铜的线粒体生物合成 缺乏类似于压力超负荷诱导的心肌细胞模型 肥大和3.为了确定ATP的功能特性 合成酶和抑制性ATP合成酶蛋白在心脏中减少， 缺铜的老鼠

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.