MECHANISMS OF RENAL ADAPTATION TO ANOXIA

肾脏适应缺氧的机制

• 批准号: 6241277
• 负责人: KAREN M GAUDIO
• 金额: $ 19.41万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241277
• 关键词: acid base balance; age difference; cellular polarity; cellular respiration; cytoskeleton; environmental adaptation; gel mobility shift assay; immature animal; intracellular transport; laboratory rat; mature animal; northern blottings; renal ischemia /hypoxia; renal tubule; sodium potassium exchanging ATPase; spectrin; stress proteins; 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.

本 PPG 的总体目标是增进我们对 细胞对缺氧的适应。 肾脏提供了独特的 有机会研究响应的基本机制 氧气的限制。 肾脏发育对细胞的影响 呼吸和对缺氧的敏感性是主要关注点 我们提出的研究。 人们常说，年轻的肾脏 成人肾脏对急性衰竭的发展具有更强的抵抗力。 然而，耐受机制尚未得到正式研究。 为了研究这个问题，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。 这将需要研究细胞之间的能量分布 运输和非运输功能；糖酵解途径，以及 作为未成熟肾小管耐受的细胞内pH值。 b) 至 评估发育期间和之后的极性和细胞骨架变化 通过确定细胞内定位的变化来判断缺氧 Na/K-ATP酶亚基和胞因子。 c) 定义自适应响应 通过研究热休克的表达和定位来应对缺氧 缺氧期间和之后的蛋白质。 为了实现这些具体目标 我们将使用综合方法来研究耐受机制 使未成熟肾小管缺氧。 研究将利用暂停 未成熟大鼠（8-10岁）经胶原酶消化后获得的肾小管 天）和成熟率（8-10 周龄）。 将使用的技术 包括再灌注期间氧气消耗率的测量，Northern 和蛋白质印迹分析、凝胶阻滞分析和免疫细胞化学 本土化。 基于这些拟议的研究，新信息 关于缺氧的结构和功能适应 将被定义，所涉及的基本机制将与 了解肾上皮细胞和其他细胞的适应性过程 器官。