MECHANISMS OF RENAL ADAPTATION TO ANOXIA

肾脏适应缺氧的机制

• 批准号: 6564738
• 负责人: NORMAN J SIEGEL
• 金额: $ 18.52万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564738
• 关键词: acid base balance; age difference; cellular polarity; cellular respiration; cytoprotection; environmental adaptation; gene induction /repression; heat shock proteins; intracellular transport; laboratory rat; northern blottings; oxygen tension; protein protein interaction; renal ischemia /hypoxia; renal tubule; sodium potassium exchanging ATPase; spectrin; transcription factor; ubiquitin; western blottings

The overall objective of this PPG is to advance our understanding of the cellular adaption to oxygen deprivation. The kidney offers a unique opportunity to investigate fundamental mechanisms which respond to limitation in oxygen. The impact of renal development on cellular respiration and susceptibility to oxygen deprivation is the primary focus of our proposed studies. It is often stated that the young kidney is more resistant to the development of acute failure that the adult kidney. However, the mechanism of tolerance have not been investigated formally. To study this problem, we propose: a) To determine the metabolic factors which contribute to the tolerance of the developing tubule to anoxia. This will entail studies of cellular energy distribution between transport and non-transport functions; the glycolytic pathway, as well as intracellular pH in the tolerance of the immature tubules. b) To evaluate polarity and cytoskeletal changes during development and after anoxia by determining the alterations in intracellular localization of Na/K-ATPase subunits, and fodrin. c) To define the adaptive response to anoxia by investigating the expression and localization of heat shock proteins during and following anoia. To accomplish these specific aims we will use an integrated approach to study the mechanisms of tolerance of the immature tubules to anoxia. Studies will utilize a suspension of tubules obtained after collagenase digestion from immature rats (age 8-10 days old) and mature rate (8-10 weeks old). Techniques that will be used include measurement of O2 consumption rates during reperfusion, Northern and Western analysis, gel retardation assay and immunocytochemical localization. Based on these proposed studies, new information concerning the structural and functional adaptation to oxygen deprivation will be defined and the basic mechanisms involved will be relevant to an understanding of adaptive processes in renal epithelial cells and other organs.

该PPG的总体目标是提高我们对 细胞对氧气剥夺的适应性。 肾脏提供了独特的 调查响应基本机制的机会 氧气的限制。 肾发育对细胞的影响 呼吸和对氧气剥夺的敏感性是主要重点 我们提出的研究。 经常说，年轻的肾脏是 比成年肾脏更能抵抗急性衰竭的发展。 但是，尚未正式研究耐受性的机制。 为了研究此问题，我们建议：a）确定代谢因素 这有助于发育中的小管对缺氧的耐受性。 这将需要研究细胞能量分布 运输和非传输功能；糖酵解途径 作为未成熟小管的耐受性的细胞内pH。 b）到 评估开发过程和之后的极性和细胞骨架变化 通过确定细胞内定位的改变 Na/k-ATPase亚基和禽类蛋白。 c）定义自适应响应 通过研究热休克的表达和定位来解决缺氧 蛋白质期间和之后的蛋白质。 实现这些特定目标 我们将使用综合方法来研究公差机制 未成熟小管的缺氧。 研究将利用暂停 来自未成熟大鼠胶原酶消化后获得的小管（年龄8-10岁） 天老）和成熟率（8-10周大）。 将使用的技术 包括在北部再灌注期间的O2消耗率的测量 以及西方分析，凝胶延迟测定和免疫细胞化学 本土化。 基于这些提议的研究，新信息 关于对氧气剥夺的结构和功能适应 将定义，涉及的基本机制将与 了解肾上皮细胞和其他的适应过程 器官。