REGULATION OF RENAL PHOSPHATE TRANSPORT BY LIPIDS

脂质对肾磷酸盐转运的调节

• 批准号: 2792621
• 负责人: HUBERT K ZAJICEK
• 金额: $ 3.02万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2792621
• 关键词: cell line; cholesterol; glycosphingolipids; immunoprecipitation; ion transport; kidney metabolism; messenger RNA; phosphates; sodium; tissue /cell culture; western blottings

lnorganic phosphate (Pi) plays an important role in a variety of critical cellular activities. Disorders of extracellular Pi concentration and Pi balance, resulting from an impairment in renal Pi reabsorption are common clinical problems in the general population. Recent studies indicate that alterations in renal cholesterol or glycosphingolipid composition are important mediators in the regulation of renal Pi reabsorption in aging, diabetes mellitus, glucocorticoid excess or deficiency, and alterations in dietary Pi or potassium. The molecular and cellular mechanisms how alterations in cholesterol or glycosphingolipids regulate renal sodium gradient-dependent Pi (Na/Pi) transport however are not known. The specific aims of the current proposal are in a cell culture model, the opossum kidney (Ok) cells, which has many of the physiological and biochemical characteristics of the renal proximal tubule: 1) to determine the acute versus chronic effects of alterations in a) cholesterol or b) glycosphingolipid composition on Na/Pi cotransport activity; 2) to determine if the alterations in cholesterol or glycosphingolipid composition modulate Na/Pi cotransport activity by a) regulating Na/Pi mRNA abundance; or by b) regulating the abundance and the expression of Na/Pi cotransporter protein at the level of the apical brush border membrane; or by c) modulating lipid-protein interactions, including changes in the mobile fraction and lateral diffusion of apical membrane Na/Pi cotransporter proteins.

lnorganic磷酸盐（PI）在多种 关键的细胞活性。细胞外PI的疾病 集中和PI平衡，肾脏受损 PI重吸收是一般的常见临床问题 人口。最近的研究表明肾脏的改变 胆固醇或糖脂组成很重要 调节肾脏PI在衰老中重吸收的介体， 糖尿病，糖皮质激素过量或缺乏，以及 膳食PI或钾的改变。分子和细胞 机制如何改变胆固醇或糖磷脂的改变 调节肾脏钠梯度依赖性PI（NA/PI）转运 但是，尚不清楚。当前建议的具体目的 在细胞培养模型中，负鼠肾（OK）细胞，该细胞 具有许多生理和生化特征 肾近端小管：1）确定急性与慢性 a）胆固醇或b）糖磷脂的改变的影响 Na/pi共转运活动的组成； 2）确定是否 胆固醇或糖磷脂成分的改变 通过a）调节Na/pi mRNA调节Na/pi共转移活性 丰富;或通过b）调节丰度和表达 Na/pi共转运蛋白在顶端刷边界的水平 膜;或c）调节脂质 - 蛋白质相互作用，包括 移动部分的变化和顶端的横向扩散 膜Na/Pi共转运蛋白。