A combination of NaCl and urea enhances survival of IMCD cells to hyperosmolality.
A combination of NaCl and urea enhances survival of IMCD cells to hyperosmolality.
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DOI：
10.1152/ajprenal.1998.274.6.f1167
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发表时间：
1998-06
期刊：
影响因子：
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通讯作者：
B. Santos;A. Chevaile;M. Hébert;J. Zagajeski;S. Gullans
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文献类型：
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作者：
B. Santos;A. Chevaile;M. Hébert;J. Zagajeski;S. Gullans
对肾髓质高渗环境的生理适应涉及一系列复杂的信号传导和基因表达事件，其中氯化钠和尿素激活不同的细胞过程。在本研究中，我们评估了 NaCl 和尿素单独和组合对小鼠内髓集合管 (mIMCD3) 细胞活力的影响。暴露于高渗性 NaCl 或尿素会导致细胞活力呈剂量和时间依赖性下降，例如 700 mosmol/kgH2O 在 24 小时内杀死 > 90% 的细胞。在这两种情况下，细胞死亡都是细胞凋亡事件。对于 NaCl，24 小时活力丧失与 4 小时 RNA 和蛋白质合成减少平行，而致死剂量的尿素对这些生物合成过程影响很小或没有影响。细胞周期分析表明，两种溶质都会导致 G2/M 期减慢。令人惊讶的是，暴露于 NaCl + 尿素组合的细胞的渗透耐受性显着增强，40% 的细胞在 900 mosmol/kgH2O 下存活。 Madin-Darby 犬肾细胞（而非人脐静脉内皮细胞）也表现出类似的渗透压耐受反应。存活率的提高与正常生物合成速率或细胞周期进展的恢复无关。然而，氯化钠 + 尿素的组合导致 Hsp70 表达发生变化，这似乎与生存相关。总之，高渗性氯化钠和尿素激活独立且互补的细胞程序，增强肾髓质上皮细胞的渗透压耐受性。
Physiological adaptation to the hyperosmolar milieu of the renal medulla involves a complex series of signaling and gene expression events in which NaCl and urea activate different cellular processes. In the present study, we evaluated the effects of NaCl and urea, individually and in combination, on the viability of murine inner medullary collecting duct (mIMCD3) cells. Exposure to hyperosmolar NaCl or urea caused comparable dose- and time-dependent decreases in cell viability, such that 700 mosmol/kgH2O killed >90% of the cells within 24 h. In both cases, cell death was an apoptotic event. For NaCl, loss of viability at 24 h paralleled decreases in RNA and protein synthesis at 4 h, whereas lethal doses of urea had little or no effect on these biosynthetic processes. Cell cycle analysis showed both solutes caused a slowing of the G2/M phase. Surprisingly, cells exposed to a combination of NaCl + urea were significantly more osmotolerant such that 40% survived 900 mosmol/kgH2O. Madin-Darby canine kidney cells but not human umbilical vein endothelial cells also exhibited a similar osmotolerance response. Enhanced survival was not associated with a restoration of normal biosynthetic rates or cell cycle progression. However, the combination of NaCl + urea resulted in a shift in Hsp70 expression that appeared to correlate with survival. In conclusion, hyperosmolar NaCl and urea activate independent and complementary cellular programs that confer enhanced osmotolerance to renal medullary epithelial cells.