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BIOSYNTHESIS OF LIVER ALKALINE PHOSPHATASE

肝脏碱性磷酸酶的生物合成

基本信息

批准号：
3463214
负责人：
NORMAN L SUSSMAN
金额：
$ 9.37万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-01-01 至 1993-12-31
项目状态：
已结题

项目摘要

Serum alkaline phosphatase (AP) is an important marker of cholestasis, a condition in which the normal flow of bile from the liver is interrupted. Cholestasis may result from physical obstruction of the biliary tree (extrahepatic cholestasis), or from poorly understood mechanisms in which bile flow is interrupted at the cellular or sub-cellular level (intrahepatic cholestasis). Irrespective of the type of cholestasis, AP activity in the liver and circulation are uniformly increased. As most of the AP in the liver is found on the canalicular membrane, it is not clear how the enzyme gets into the circulation. Two possible explanations exist: a secreted form of the enzyme might be synthesized de novo, or membrane-anchored AP may migrate along the intercellular space towards the sinusoidal membrane where it is cleaved by phospholipase C. These two theories are not mutually exclusive. This proposal aims at answering some of the questions related to AP synthesis and secretion by the liver. Specifically, the studies will focus on: 1. Whether a secreted form of AP is synthesized by the liver. 2. How the increased synthesis of AP is mediated. 3. The process of AP attachment to the microsomal membrane. The techniques that will be used include histochemical staining of liver sections affinity chromatography, in vitro transcription and translation, Northern blots, tissue culture and precursor labeling. The significance of the work lies in gaining an understanding into the process of AP synthesis as it relates to the liver in normal and diseased states.

血清碱性磷酸酶（AP）是一个重要的标志物，胆汁淤积，一种胆汁从肝内正常流出的情况，肝脏被打断了。胆汁淤积可能是由于身体胆道系统阻塞（肝外胆汁淤积），或胆汁流动中断的机制知之甚少，细胞或亚细胞水平（肝内胆汁淤积）。不管是什么类型的胆汁淤积，肝脏和循环中的AP活性均匀增加由于肝脏中的大多数AP都位于小管膜，目前尚不清楚酶如何进入小管膜。流通存在两种可能的解释：酶可以从头合成，或者膜锚定AP 可以沿着细胞间隙向正弦曲线迁移膜，在那里它被磷脂酶C切割。这两理论并不是相互排斥的。这项建议旨在回答与行动方案综合有关的一些问题，由肝脏分泌。具体而言，这些研究将侧重于： 1. AP的分泌形式是否由肝脏合成。 2. AP合成的增加是如何介导的。 3. AP附着于微粒体膜的过程。将使用的技术包括组织化学染色，肝切片亲和层析，体外转录和翻译、北方印迹、组织培养和前体标记。这项工作的意义在于了解 AP合成的过程，因为它与正常人的肝脏有关，和病态的国家