CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY

描述：此修订后的应用程序建议研究假设 铜缺乏对心脏的影响就好像是 由于一种影响线粒体的线粒体遗传病 生物发生，并且这种效应是通过上调 转录因子，这些转录因子负责病理和 生物化学。这些变化包括细胞色素c氧化酶的减少。 核编码肽的(CCO)活性和绝对量 亚单位。此外，ATP合成酶的德尔塔亚基显著 ATPase的e亚基显著增加。这些 改变会导致线粒体的生物发生和随后的增加 在铜缺乏的大鼠的心脏中观察到的心脏质量。 因此，这项提案将审查三个具体目标：1.确定是否 几种转录因子的表达及DNA结合活性 已知的调节核和线粒体编码基因的因子有 铜缺乏的大鼠心脏中的含量增加。2.确定是否 铜线粒体生物发生中的基因调控程序 缺乏症类似于压力超负荷诱导的心肌细胞模型 肥大和3.确定ATP的功能特性 心脏合酶和抑制三磷酸腺苷合酶蛋白减少 缺铜大鼠。

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.