Santos Bento C, Pullman James M, Chevaile Alejandro, Welch William J, Gullans Steven R
Department of Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston 02115, USA.
Am J Physiol Renal Physiol. 2003 Mar;284(3):F564-74. doi: 10.1152/ajprenal.00058.2002. Epub 2002 Oct 29.
Renal medullary cells are exposed to elevated and variable osmolarities and low oxygen tension. Despite the harsh environment, these cells are resistant to the effects of many harmful events. To test the hypothesis that this resistance is a consequence of these cells developing a stress tolerance phenotype to survive in this milieu, we created osmotically tolerant cells [hypertonic (HT) cells] by gradually adapting murine inner medullary collecting duct 3 cells to hyperosmotic medium containing NaCl and urea. HT cells have a reduced DNA synthesis rate, with the majority of cells arrested in the G(0)/G(1) phase of the cell cycle, and show constitutive expression of heat shock protein 70 that is proportional to the degree of hyperosmolarity. Unlike acute hyperosmolarity, chronic hyperosmolarity failed to activate MAPKs. Moreover, HT cells acquired protein translational tolerance to further stress treatment, suggesting that HT cells have an osmotolerant phenotype that is analogous to thermotolerance but is a permanent condition. In addition to osmotic shock, HT cells were more resistant to heat, H(2)O(2), cyclosporin, and apoptotic inducers, compared with isotonic murine inner medullary duct 3 cells, but less resistant to amphotericin B and cadmium. HT cells demonstrate that in renal medullary cells, hyperosmotic stress activates biological processes that confer cross-tolerance to other stressful conditions.
肾髓质细胞暴露于升高且变化的渗透压以及低氧张力环境中。尽管环境恶劣，但这些细胞对许多有害事件的影响具有抗性。为了验证这种抗性是这些细胞形成应激耐受表型以在该环境中存活的结果这一假说，我们通过将小鼠内髓集合管3细胞逐渐适应含有氯化钠和尿素的高渗培养基，创建了渗透压耐受细胞（高渗细胞）。高渗细胞的DNA合成速率降低，大多数细胞停滞在细胞周期的G(0)/G(1)期，并显示出与高渗程度成比例的热休克蛋白70的组成性表达。与急性高渗不同，慢性高渗未能激活丝裂原活化蛋白激酶。此外，高渗细胞获得了对进一步应激处理的蛋白质翻译耐受性，这表明高渗细胞具有类似于热耐受性但为永久性状态的渗透压耐受表型。除了渗透压休克外，与等渗的小鼠内髓集合管3细胞相比，高渗细胞对热、过氧化氢、环孢素和凋亡诱导剂更具抗性，但对两性霉素B和镉的抗性较低。高渗细胞表明，在肾髓质细胞中，高渗应激激活了赋予对其他应激条件交叉耐受性的生物学过程。
