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ROLE OF THE GOLGI APPARATUS IN BILE ACID SECRETION

高尔基体在胆汁酸分泌中的作用

基本信息

批准号：
3152801
负责人：
BECCA C FLEISCHER
金额：
$ 7.14万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-12-01 至 1986-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152801
关键词：
Golgi apparatus affinity chromatography autoradiography cell membrane cytoplasm dialysis electron microscopy liver disorder liver function liver metabolism radiotracer secretion

项目摘要

The aim of this research is to determine what, if any, is the role of the Golgi apparatus in bile acid secretion in the liver. We have found that purified Golgi from rat liver, as well as plasma membranes and cytoplasm, contain high affinity binding sites for taurocholate. We will characterize further what proteins are involved in this binding and determine what relationship, if any, exists between binding proteins of Golgi, plasma membranes and the cytoplasm. The ability of the various subcellular organelles of liver to take up bile salts will be investigated using filtration techniques. We have developed such techniques for studying nucleotide transport in Golgi vesicles. If uptake is found in isolated Golgi and/or other subcellular organelles, we will characterize the uptake with respect to its kinetic parameters and determine how its properties relate to the high and low affinity binding sites observed in these fractions. Finally, using rat liver cell suspensions, we will perturb albumin secretion at the level of the Golgi apparatus and determine the effects on bile salt secretion. These studies will help define the subcellular pathway of bile acid secretion in liver and thus have a direct bearing on medical problems such as cholestasis, gallstones and their treatment, cirrhosis, and liver diseases in general. The metabolism and secretion of bile acids also affects cholesterol metabolism in the liver and thus this research is also relevant to atherosclerosis.

这项研究的目的是确定，如果有的话，高尔基体在肝脏中分泌胆汁酸。我们发现从大鼠肝脏纯化的高尔基体，以及质膜和细胞质，含有牛磺胆酸盐的高亲和力结合位点。我们将描述进一步了解哪些蛋白质参与了这种结合，并决定了高尔基体、血浆和线粒体的结合蛋白之间存在着联系，膜和细胞质。各种亚细胞的能力肝细胞器采取胆汁盐将研究使用过滤技术。我们已经开发了这样的技术来研究高尔基体囊泡中的核苷酸转运。如果在孤立的高尔基体和/或其他亚细胞器，我们将表征摄取关于它的动力学参数，并确定它的性质如何与在这些细胞中观察到的高和低亲和力结合位点有关分数最后，使用大鼠肝细胞悬液，我们将扰动在高尔基体水平分泌白蛋白，并确定对胆盐分泌的影响。这些研究将有助于确定胆汁酸在肝脏分泌的亚细胞途径，从而有一个直接与诸如胆汁淤积、胆结石及其治疗，肝硬化和一般肝病。代谢和胆汁酸的分泌也影响肝脏中的胆固醇代谢因此这项研究也与动脉粥样硬化有关。