RESPONSE OF RENAL CELLS TO OSMOTIC STRESS

肾内髓质血液渗透压高，随尿浓度变化。NaCl和尿素均升高。髓质细胞显然能在这种不利的环境中存活并发挥功能。正在进行的研究关注于了解所涉及的机制。当细胞受到高盐环境的压力时，它们通常会积累具有渗透活性的有机溶质（“渗透物”），以维持有利的内部环境，同时调节其体积。我们确定肾髓内细胞中的有机渗透物为甘油酰胆碱（GPC）、甜菜碱、山梨醇、牛磺酸和肌醇，并表明渗透物水平随尿浓度（可能还有髓盐和尿素浓度）而变化。我们现在正在用肾细胞培养和活体动物来研究这些有机渗透物的渗透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细胞增殖培养中的细胞周期阻滞和细胞凋亡。我们正在研究其中的机制，包括p53的作用。

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. 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.