THE TRANSPORT OF CALCIUM

钙的运输

• 批准号: 3224314
• 负责人: David Schachter
• 金额: $ 13.99万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-04-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3224314
• 关键词: adenosinetriphosphatase; basolateral membrane; bone metabolism disorder; calcium channel; complementary DNA; hormone regulation /control mechanism; intestinal mucosa; laboratory mouse; laboratory rabbit; laboratory rat; malabsorption; messenger RNA; radiotracer; vitamin D; vitamin D deficiency

The research will characterized the molecular basis of calcium transport across the intestinal mucosa and its regulation by vitamin D. A vitamin D-dependent membrane-associated protein, IMCAL, has been isolated from rat duodenal mucosa. The protein binds calcium with high affinity, and its content in the mucosa correlates closely with the active transport of the cation. The working hypothesis, accordingly, is that IMCAL is a mediator and regulator of the transport. The present investigation will continue the biochemical characterization of the protein, determine its subcellular distribution in intestinal enterocytes and explore its functional role in relation to specific membrane calcium mechanisms. The sequence of the protein will be determined by cDNA cloning and the regulation of IMCAL-specific mRNA studied in intestinal mucosa. Biosynthesis and turnover of the mucosal protein and its regulation by vitamin D will be characterized by examining the incorporation of radioactive amino acids and other precursors. The subcellular distribution of IMCAL in enterocytes will be characterized by isolation of the organelles and immunoassays. The molecular functions of IMCAL will be explored by modulating the tissue content in vivo (vitamin D deficiency versus repletion; low versus high calcium diets), isolating membrane vesicles (microvillus membranes and basolateral membranes) and testing specific membrane functions, including 45Ca uptake, ATP- dependent 45Ca accumulation, calcium-dependent adenosine triphosphatase, and calcium binding. The possibility of intracellular transport of calcium via a specialized membrane vesicle rich in IMCAL will be explored. These studies should contribute to an understanding of a number of human disorders including malabsorption syndromes, metabolic bone disorders and cardiovascular diseases such as essential hypertension.

该研究将表征钙转运的分子基础 穿过肠粘膜及其对维生素D的调节。维生素 D依赖性膜相关蛋白IMCAL已从从中分离出来 大鼠十二指肠粘膜。 蛋白质与高亲和力结合钙，并且 它在粘膜中的内容与主动传输密切相关 阳离子。 因此，工作假设是Imcal是一个 运输的调解人和调节器。 本调查将 继续蛋白质的生化表征，确定其 肠肠上皮细胞中的亚细胞分布并探索其 与特定膜钙机制有关的功能作用。 蛋白质的序列将由cDNA克隆和 在肠粘膜中研究的IMCAL特异性mRNA的调节。 粘膜蛋白的生物合成和周转及其调节 维生素D的特征是检查 放射性氨基酸和其他前体。 亚细胞 肠细胞中IMCAL的分布将以隔离为特征 细胞器和免疫测定。 IMCAL的分子函数 将通过调节体内组织含量来探索（维生素D 缺乏与补充；低钙饮食与高钙饮食），隔离 膜囊泡（微绒毛膜和基底外侧膜）和 测试特定的膜功能，包括45CA吸收，ATP- 依赖45CA积累，依赖钙的腺苷三磷酸酶， 和钙结合。 细胞内运输的可能性 通过富含Imcal的专门膜囊泡的钙将是 探索。 这些研究应该有助于理解 人类疾病的数量包括吸收不良综合征，代谢 骨骼疾病和心血管疾病（例如必需） 高血压。