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CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY

缺铜时的心脏特征

基本信息

批准号：
3347051
负责人：
DENIS M MEDEIROS
金额：
$ 7.69万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-04-01 至 1994-07-31
项目状态：
已结题

项目摘要

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（主要研究者的摘要）：心脏肥大是在喂食缺铜饮食的几种动物中观察到。一些变化类似于人类心脏病。确定机制缺铜大鼠出现心脏肥大的原因是本研究的长期目标。第二个目标是确定铜补充逆转肥大的程度和过程。这方法是从组织学和瓣膜研究心肌和瓣膜生化方面并将这些变化联系起来器官功能和能量潜在变化的充分状态收费。分子量约为 23 K 的多肽似乎是在缺陷大鼠中减少，可能是细胞色素 C 的亚基 III 氧化酶。这种酶的活性降低和线粒体的改变存在于一些人类心脏病中。使用微测序技术中，该多肽存在于对照中，但在缺陷中不存在大鼠将被鉴定，并且该多肽的调节作为使用放射性示踪剂进行铜缺乏和补充研究的功能和分子生物学技术。蛋白质合成速率和降解以及铜是否调节转录的 23 K 水平将被研究。心脏铜补充的任何逆转铜缺乏时观察到的损害将使用透射率进行评估电子显微镜。除了肌肉改变外，瓣膜结构也发生改变铜缺乏症发生改变，结缔组织密度降低所证明网络。虽然胶原纤维的组织学结构不是改变后，胶原蛋白合成的速率可能会改变。减少或心脏瓣膜松软的结缔组织有缺陷是一些人的问题人类疾病的类型，例如埃勒斯-当洛斯综合征和马凡综合征。缺乏和补充研究可能会揭示对这两种比率的一些影响胶原蛋白合成和异构体表达，将使用技术已经描述过。这些研究也可能具有临床意义适用于可能拥有某种形式缺陷的个人的申请铜代谢或缺乏。