FISH MODEL FOR THE STUDY OF HEPATIC COPPER METABOLISM

用于研究肝铜代谢的鱼模型

• 批准号: 3251347
• 负责人: JOHN M FRAZIER
• 金额: $ 10.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3251347
• 关键词: aquatic organism; atomic absorption spectrometry; biological models; cell membrane; centrifugation; copper; density gradient ultracentrifugation; eukaryote; genetic regulation; hepatolenticular degeneration; liver metabolism; mathematical model; membrane permeability; metal metabolism; metalloproteins; model design /development; radiotracer; species difference

The overall objective of this research program is to develop a fish model for the investigation of hepatic copper metabolism in order to advance our understanding of the molecular kinetics of copper in eukaryotic cells. Copper is a highly toxic metal and alterations in its normal metabolism result in severe cellular dysfunction, such as expressed in Wilson's disease. The white perch (Morone americana) accumulates exceptionally high copper concentrations in the liver (greater than 1000 Mug/g wet weight) under conditions of natural exposure. These levels are greatly in excess of hepatic copper concentrations observed in Wilson's disease patients. A closely related fish species, the striped bass (Morone saxatilis), exhibits hepatic copper levels similar to mammals and will serve as controls. The specific aim of this project is to determine the mechanisms which account for the abnormal accumulation of copper in white perch. Experimental studies using isolated hepatocytes and purified membrane preparations from these two fish species will investigate the role of membrane transport and intracellular protein binding in copper accumulation. A unique feature of this study is that the two fish species can be crossbred to produce hybrids which will allow us to investigate the genetic control of the accumulation factors. It is expected that this fish model will contribute new knowledge concerning the mechanisms which control copper kinetics in eukaryotic cells.

这项研究计划的总体目标是开发一种鱼类模型， 为研究肝铜代谢，以推进我们的 了解铜在真核细胞中的分子动力学。 铜是一种剧毒金属，其正常代谢的改变 导致严重的细胞功能障碍，如在Wilson's 疾病 白色鲈鱼（Morone americana） 肝脏中的铜浓度（大于1000 μ g/g湿重） 在自然暴露的条件下。 这些水平大大超过 肝铜浓度在肝豆状核变性患者观察。 一 密切相关的鱼类，条纹鲈鱼（Morone saxatilis），显示 肝脏铜水平与哺乳动物相似，并将作为对照。 的 该项目的具体目标是确定机制， 白色鲈鱼体内铜的异常积累 实验 研究使用分离的肝细胞和纯化的膜制备物， 这两种鱼类将研究膜运输的作用， 细胞内蛋白结合在铜积累中的作用。 的独特特征 这项研究表明，这两种鱼可以杂交产生杂交种 这将使我们能够研究基因控制的积累 因素 预计这种鱼类模型将贡献新的知识 关于控制真核细胞中铜动力学的机制。