Response Of Renal Cells To Osmotic Stress

肾细胞对渗透压的反应

• 批准号: 6690489
• 负责人: MAURICE BENJAM BURG
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6690489
• 关键词: Mammalia; apoptosis; blood osmolarity; cell cycle; cell cycle proteins; cell morphology; cell osmotic pressure; kidney cell; kidney function; p53 gene /protein; renal medulla; tissue /cell culture; transcription factor

The osmolality of the blood in the renal inner medulla is high and varies with the urinary concentration. Both NaCl and urea are elevated. The medullary cells evidently survive and function in this adverse environment. The ongoing studies are concerned with understanding the mechanisms involved. When cells are stressed by a high salt environment, they generally accumulate osmotically active organic solutes ("osmolytes") in order to maintain a favorable internal milieu, while regulating their volume. We identified the organic osmolytes in renal inner medullary cells as glycerophosphocholine (GPC), betaine, sorbitol, taurine, and inositol, and showed that the osmolyte levels varied with urine concentration (and, presumably, medullary salt and urea concentrations). We are now using renal cell cultures and living animals to study the mechanism and control of osmoregulatory accumulation of these organic osmolytes, including the transcription factor (TonEBP/OREBP) that is involved. In addition, the acute response to high osmolality may include cell cycle arrest and apoptosis in proliferating cultures of renal medullary cells. We are studying the mechanisms involved, including the role of p53, p38, and GADD proteins.

肾内髓质的血液渗透压很高，并随尿浓度而变化。NaCl和尿素均升高。显然，髓细胞在这种不利的环境中存活并发挥作用。正在进行的研究涉及了解所涉及的机制。当细胞受到高盐环境的应激时，它们通常积累具有抗氧化活性的有机溶质（“渗透压物”），以维持有利的内部环境，同时调节它们的体积。我们确定了有机渗透压在肾内髓细胞甘油磷酸胆碱（GPC），甜菜碱，山梨醇，牛磺酸，肌醇，并表明渗透压水平随尿液浓度（和，大概，髓盐和尿素浓度）。我们现在正在使用肾细胞培养和活体动物来研究这些有机渗透剂，包括参与的转录因子（TonEBP/OREBP）的调节积累的机制和控制。此外，对高渗透压的急性反应可能包括肾髓质细胞增殖培养物中的细胞周期停滞和细胞凋亡。我们正在研究相关的机制，包括p53，p38和GADD蛋白的作用。