CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY
CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY
批准号:
3347051
负责人:
DENIS M MEDEIROS
金额:
$7.69万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-04-01 至 1994-07-31
关键词:
cell transformation 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 microorganism genetics mitochondria molecular cloning myocardium nucleic acid probes nutrition related tag pathogenic diet protein metabolism proteins transmission electron microscopy
中文摘要
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。
英文摘要
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.
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DOI:
10.1152/ajpheart.1993.264.6.h2154
发表时间:
1993-06
期刊:
The American journal of physiology
影响因子:
--
作者:
[R. Vadlamudi;R. McCormick;D. Medeiros;J. Vossoughi;M. Failla]
通讯作者:
R. Vadlamudi;R. McCormick;D. Medeiros;J. Vossoughi;M. Failla
Copper deficiency in a genetically hypertensive cardiomyopathic rat: electrocardiogram, functional and ultrastructural aspects.
遗传性高血压心肌病大鼠的铜缺乏:心电图、功能和超微结构方面。
DOI:
10.1093/jn/121.7.1026
发表时间:
1991
期刊:
The Journal of nutrition
影响因子:
--
作者:
[Medeiros,DM, Liao,Z, Hamlin,RL]
通讯作者:
Hamlin,RL
Myofibrillar and nonmyofibrillar myocardial proteins of copper-deficient rats.
缺铜大鼠的肌原纤维和非肌原纤维心肌蛋白。
DOI:
10.1093/jn/119.11.1683
发表时间:
1989
期刊:
The Journal of nutrition
影响因子:
--
作者:
[McCormick,RJ, Ovecka,GD, Medeiros,DM]
通讯作者:
Medeiros,DM
Comparative aspects of cardiac ultrastructure, morphometry, and electrocardiography of hearts from rats fed restricted dietary copper and selenium.
限制膳食铜和硒喂养的大鼠心脏超微结构、形态测定和心电图的比较。
DOI:
10.1007/bf02790067
发表时间:
1994
期刊:
Biological trace element research
影响因子:
3.9
作者:
[Wildman,RE, Medeiros,DM, Jenkins,J]
通讯作者:
Jenkins,J
Diets containing corn oil, coconut oil and cholesterol alter ventricular hypertrophy, dilatation and function in hearts of rats fed copper-deficient diets.
含有玉米油、椰子油和胆固醇的饮食会改变喂食缺铜饮食的大鼠的心室肥厚、扩张和功能。
DOI:
10.1093/jn/123.6.1150
发表时间:
1993
期刊:
The Journal of nutrition
影响因子:
--
作者:
[Jenkins,JE, Medeiros,DM]
通讯作者:
Medeiros,DM
Kansas Bridges to the Future
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-
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-
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-
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海外基金