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INTESTINAL CA2 + TRANSPORT: VIT. D-DEPENDENT MECHANISMS

肠道 CA2 运输：VIT。

基本信息

批准号：
3152494
负责人：
MILTON M WEISER
金额：
$ 7.14万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
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：
1983-04-01 至 1986-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152494
关键词：
1,25 dihydroxycholecalciferol Golgi apparatus basolateral membrane calcium disorder calcium metabolism cell membrane dietary calcium gastrointestinal epithelium gastrointestinal nutrient absorption membrane permeability messenger RNA nephrolithiasis nutrition related tag osteoporosis vitamin D

项目摘要

In previous studies concerning the mechanism of vitamin D-dependent Ca2+ transport across the intestine, we prepared membrane vesicles from rat intestinal epithelial cells and observed that Golgi membrane vesicles demonstrated the highest Ca++ uptake when compared with lateral-basal and microvillus membrane vesicles. Golgi Ca++ uptake was specifically dependent on 1,25(OH)2D3, the active metabolite of vitamin D. We postulate that Golgi Ca++ uptake may represent either a Ca++ sequestration mechanism or a site where Ca++ transport related factors are prepared for plasma membrane remodeling. The specific aims of this research proposal are to determine: 1) the molecular nature of the 1,25(OH)2D3 dependent change in Ca++ uptake by Golgi, 2) the mechanism by which 1,25(OH)2D3 alters Ca++ uptake by Golgi, and 3) the relationship of Golgi Ca++ uptake to intestinal Ca++ transport. The kinetics of Ca++ binding by Golgi membrane vesicles will be analyzed. The molecules responsible for the 1,25(OH)2D3 dependent Ca++ binding by Golgi will be identified, isolated and characterized. Attempts will be made to determine if 1,25(OH)2D3 stimulates the synthesis and/or appearance of proteins in Golgi or affects Golgi lipids. The effect of 1,25(OH)2D3 on intestinal messenger RNA, particularly in relationship to Golgi Ca++ uptake, will be evaluated using in vitro cell free translation systems. Finally, the movement of factors associated with Golgi Ca++ binding, as part of a process of plasma membrane remodeling will be studied. These experiments will contribute to an understanding of the control of intestinal Ca++ transport. Regulation of intestinal calcium transport is fundamental to calcium homostasis. Therefore, these studies will help in understanding the pathophysiology of osteoporosis, kidney stones, and the effect of intestinal diseases on calcium absorption and derangements of calcium metabolism.

在以往关于维生素D依赖性钙离子机制的研究中，为了研究跨肠转运，我们制备了大鼠膜囊泡，肠上皮细胞，并观察到高尔基膜囊泡，与外侧-基底相比，微绒毛膜小泡。高尔基体Ca ++摄取是特异性的，依赖于维生素D的活性代谢物1，25（OH）2D3。我们推测高尔基体对Ca ++的摄取可能代表了Ca ++的螯合机制，或制备用于血浆的Ca ++转运相关因子的位点膜重塑本研究建议的具体目标是确定：1）1，25（OH）2D3依赖性变化的分子性质， 1，25（OH）_2D_3改变高尔基体Ca~（++）吸收的机制高尔基体对Ca~（++）的摄取与小肠Ca~（++）的关系 Ca ++转运。高尔基体膜囊泡与Ca~（++）结合的动力学将被分析。负责1，25（OH）2D3依赖性的分子将对高尔基体的Ca ++结合进行鉴定、分离和表征。将尝试确定1，25（OH）2D3是否刺激合成和/或蛋白质在高尔基体中的出现或影响高尔基体脂质。效果 1，25（OH）2D3对肠道信使RNA的影响，特别是与高尔基体Ca ++摄取，将使用体外无细胞翻译进行评价系统. 最后，与高尔基体Ca ++相关的因子的运动结合，作为质膜重塑过程的一部分，研究了这些实验将有助于理解控制肠道Ca ++转运。肠钙调节转运是钙稳态的基础。这些研究将有助于了解骨质疏松症的病理生理学，肾脏结石，以及肠道疾病对钙吸收的影响，钙代谢紊乱