CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY

缺铜时的心脏特征

• 批准号: 3347043
• 负责人: DENIS M MEDEIROS
• 金额: $ 10.28万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3347043
• 关键词: cellular respiration; collagen; complementary DNA; connective tissue metabolism; copper; cytochrome oxidase; diet therapy; dietary trace element; gel electrophoresis; genetic library; genetic transcription; heart dimension /size; heart enlargement; heart function; heart metabolism; heart valves; hypocupremia; laboratory rat; messenger RNA; metal metabolism; mitochondria; molecular cloning; myocardium; nucleic acid probes; nutrition related tag; pathogenic diet; protein metabolism

DESCRIPTION (Principal Investigator's Abstract): Cardiac hypertrophy is observed in several animal species fed copper deficient diets. Some of the changes resemble human cardiac pathologies. Determining the mechanism(s) by which cardiac hypertrophy occurs in the copper deficient rat is the long-term objective of this study. A second objective is to determine the extent and processes by which copper repletion reverses hypertrophy. The approach is to study both the myocardium and valves from histological and biochemical aspects and to relate these changes in both depleted and repleted states to potential alterations in organ function and energy charge. A polypeptide of approximately 23 K molecular weight appears to be diminished in deficient rats and could be subunit III of cytochrome C oxidase. Decreased activity of this enzyme and alteration of mitochondria are present in some human heart diseases. Using microsequencing techniques, the polypeptide present in controls but absent in deficient rats will be identified and the regulation of this polypeptide as a function of both copper deficiency and repletion studies using radiotracers and molecular biology techniques. The rate of protein synthesis and degradation and whether copper regulates the 23 K at the transcriptional level will be studied. Any reversal with copper repletion of the cardiac damage observed in copper deficiency will be evaluated using transmission electron microscopy. In addition to muscle alterations, valve structure is altered in copper deficiency as evidenced by a less dense connective tissue network. While the histological structure of the collagen fibril is not altered, the rate of collagen synthesis may be changed. Decreased or defective connective tissue of floppy heart valves is a problem in some types of human disorders such as Ehlers-Danlos and Marfan syndromes. Deficiency and repletion studies may reveal some effect upon both rate of collagen synthesis and isoform expression and will be evaluated using techniques already described. These studies may also have clinical applications for those individuals who may possess some form of defective copper metabolism or deficiency.

描述(首席研究人员摘要)：心肌肥厚 在饲喂铜缺乏饲料的几种动物中观察到。其中一些 这些变化类似于人类的心脏病理。确定机制(S) 缺铜大鼠心肌肥厚的发生机制是 这项研究的长期目标。第二个目标是确定 铜补充逆转肥厚的程度和过程。这个 方法是从组织学和组织学角度研究心肌和瓣膜 生化方面的变化，并将这些变化与耗竭和 器官功能和能量的潜在变化的重复状态 充电。一种约23K分子量的多肽似乎是 在缺乏的大鼠中减少，可能是细胞色素C的亚基III 氧化物酶。该酶活性降低和线粒体改变 存在于某些人类心脏病中。使用微测序 技术，在对照中存在但在缺陷中缺失的多肽 将对大鼠进行鉴定，并将这种多肽作为一种 用放射性示踪剂研究铜缺乏和补充的作用 和分子生物学技术。蛋白质合成的速度和 降解以及铜是否在转录水平上调节23K 水平将被研究。任何心脏铜再充盈的逆转 在铜缺乏中观察到的损害将使用传输进行评估 电子显微镜。除了肌肉变化，瓣膜结构也是 铜缺乏改变，表现为密度较低的结缔组织 网络。而胶原原纤维的组织结构不是 改变，胶原蛋白的合成速度可能会改变。减少或 软性心脏瓣膜的结缔组织缺陷在某些情况下是一个问题 人类疾病的类型，如埃勒斯-丹洛斯综合征和马凡综合征。 缺乏和补充研究可能揭示对这两个比率的一些影响 胶原蛋白的合成和异构体的表达，将使用 技术已经描述过了。这些研究也可能具有临床意义 为那些可能拥有某种形式的缺陷的个人申请 铜代谢或缺乏。