MEMBRANES AND PHOSPHOLIPIDS IN RENAL HYPERPLASIA

肾增生中的膜和磷脂

• 批准号: 3236009
• 负责人: FREDERICK Gary TOBACK
• 金额: $ 22.01万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3236009
• 关键词: acid phosphatase; aminoacid; autoradiography; beta galactosidase; beta glucuronidase; bioenergetics; cell differentiation; cycloheximide; dietary potassium; electron microscopy; electron transport; enzyme mechanism; histochemistry /cytochemistry; hypokalemia; immunochemistry; kidney hyperplasia; kidney metabolism; laboratory rat; lipid metabolism; lysosomes; membrane lipids; membrane permeability; membrane reconstitution /synthesis; mitochondria; nutrition related tag; organelles; oxidative phosphorylation; phagocytosis; phospholipids; potassium deficiency; protein metabolism; radiotracer; renal cortex; renal medulla; thin layer chromatography

The objective of the proposed research is to elucidate mechanisms which regulate membrane formation, organelle biogenesis, cellular growth and energy metabolism in the kidneys of potassium (K)-depleted rats. Kidneys of K-depleted rats offer an extraordinary mode system for study of organ growth that can be modulated by dietary changes. The induction of lysosome formation in the renal medulla of K-depleted rats provides a unique opportunity to study the factors which regulate lysosome biogenesis and enzyme formation. The sensitivity of mitochondrial oxidative phosphorylation to alterations in dietary K intake permits study of the role of this ion in the regulation of cellular energy production. Using growing tissue from K-depleted rats we plan to characterize the role of K as a modulator of phospholipid and protein precursor uptake and the enzymatic reactions of phospholipid biosynthesis. The kinetics of synthesis and degradation of a specific lysosomal enzyme will be defined by immunoprecipitation analysis and the cellular locus of lysosome formation will be studied during lysosome biogenesis and regression in the renal papilla of K-depleted and K-repleted rats. The role of K and other cations in mitochondrial energy production and in the integration of glycolysis and respiration will be examined in cells in the inner stripe of the renal red medulla which undergo adenomatous hyperplasia during K depletion. Since alterations in K balance occur in many disease states, elucidation of the biochemical and molecular events that are consequences of this disturbance is of basic importance to medicine and disordered biology.

拟议研究的目的是阐明调节机制 膜形成、细胞器生物发生、细胞生长和能量代谢 钾 (K) 耗尽的大鼠的肾脏中。 缺钾大鼠的肾脏为器官研究提供了非凡的模式系统 可以通过饮食改变来调节生长。 溶酶体的诱导 缺钾大鼠肾髓质的形成提供了独特的机会 研究调节溶酶体生物合成和酶形成的因素。 线粒体氧化磷酸化对改变的敏感性 膳食钾摄入量允许研究该离子在调节中的作用 细胞能量产生。 我们计划利用 K 耗尽大鼠的生长组织来表征 K 的作用 作为磷脂和蛋白质前体摄取和酶促的调节剂 磷脂生物合成反应。 合成动力学和 特定溶酶体酶的降解定义为 免疫沉淀分析和溶酶体形成的细胞位点将 在肾乳头的溶酶体生物发生和消退过程中进行研究 缺钾和补充钾的大鼠。 K 和其他阳离子的作用 线粒体能量产生以及糖酵解和糖酵解的整合 将在肾红内条纹的细胞中检查呼吸作用 髓质在 K 耗竭期间发生腺瘤性增生。 由于钾平衡的改变发生在许多疾病状态下，因此需要阐明 这种干扰造成的生化和分子事件是 对医学和无序生物学的基本重要性。