CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY

描述（主要研究者摘要）：心脏肥大是 在几种动物中观察到铜缺乏饮食。 一些 变化类似于人类心脏病理学。 确定机制 缺铜大鼠心肌肥厚的机制是 本研究的长期目标。 第二个目标是确定 程度和过程，铜补充逆转肥大。 的 方法是研究心肌和瓣膜从组织学和 生物化学方面，并将这些变化与耗尽和 器官功能和能量的潜在变化 消费标准. 分子量约为23 K的多肽似乎是 可能是细胞色素C亚单位III 氧化酶。 这种酶的活性降低和线粒体的改变 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不存在的多肽 将对大鼠进行鉴定，并将这种多肽的调节作为 用放射性示踪剂研究铜缺乏和补充的功能 和分子生物学技术。 蛋白质合成的速率和 降解和铜是否调节23 K的转录 水平将被研究。 任何逆转与铜充盈的心脏 在铜缺乏中观察到的损伤将使用透射率进行评估。 电镜 除了肌肉改变，瓣膜结构也 在铜缺乏中改变，表现为结缔组织密度降低 网络 虽然胶原纤维的组织结构不是 改变后，胶原蛋白合成的速率可能会改变。 减少或 松软心脏瓣膜的有缺陷的结缔组织是一些人的问题， 人类疾病类型，如Ehlers-Danlos和Marfan综合征。 缺乏和充实的研究可能会揭示一些影响， 胶原合成和同种型表达，并将使用 已经描述的技术。 这些研究也可能具有临床意义。 对于那些可能拥有某种形式的缺陷的个人的申请 铜代谢或缺乏。

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.