Long-term adaptation of renal cells to hypertonicity: role of MAP kinases and Na-K-ATPase
Long-term adaptation of renal cells to hypertonicity: role of MAP kinases and Na-K-ATPase
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DOI：
10.1152/ajprenal.2001.280.5.f768
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发表时间：
2001-05-01
影响因子：
4.2
通讯作者：
Berl, T
中科院分区：
文献类型：
--
作者：
Capasso, JM;Rivard, CJ;Berl, T
当暴露于高渗环境时，培养的肾细胞存活率低。我们培养了适应600和900 mosmol/kgH的内髓收集管细胞细胞系(2)。我们在适应细胞中研究了丝裂原活化蛋白（MAP）激酶家族的三个模块。这些细胞的细胞外信号调节激酶、c-Jun NH(2)末端激酶、p38 MAP激酶蛋白或基础活性均未增加。当进一步增加强直性时，这些激酶的激活减弱，这不是由于磷酸酶活性增强。相比之下，适应高张力的细胞显示Na-K-ATPase表达显著增加（5倍），而瓦阿因敏感的Na-K-ATPase活性显著增加（10倍）。这些变化在恢复等渗状态时是可逆的。在适应600 mosmol/kgH(2)O的细胞中，用尿素替代300 mosmol/kgH(2)O的NaCl会导致na - k - atp酶显著下降，无法维持细胞系。在适应900 mosmol/kgH(2)O的细胞中，用NaCl代替尿素没有改变na - k - atp酶的表达，也没有改变细胞的活力。研究了na - k - atp酶在无水小鼠肾乳头（尿渗透压2,900 mosmol/ kgH(2)O）和饮水葡萄糖小鼠（550 mosmol/ kgH(2)O）中的体内调节。饮水量增加与na - k - atp酶表达减少30%相关（P< 0.02, n = 6），表明该酶在体内受渗透调节。我们得出的结论是，尽管MAP激酶在急性强直性变化的反应中发挥作用，但它们不是慢性适应性反应的核心。相反，在这种情况下，存在其他渗透保护蛋白的上调，其中na - k - atp酶似乎是适应性过程的重要组成部分。
Renal cells in culture have low viability when exposed to hypertonicity. We developed cell lines of inner medullary collecting duct cells adapted to live at 600 and 900 mosmol/kgH(2)O. We studied the three modules of the mitogen-activated protein (MAP) kinase family in the adapted cells. These cells had no increase in either extracellular signal-regulated kinase, c-Jun NH(2)-terminal kinase, or p38 MAP kinase protein or basal activity. When acutely challenged with further increments in tonicity, they had blunted activation of these kinases, which was not due to enhanced phosphatase activity. In contrast, the cells adapted to the hypertonicity displayed a marked increment in Na-K-ATPase expression (5-fold) and ouabain-sensitive Na-K-ATPase activity (10-fold). The changes were reversible on return to isotonic conditions. Replacement of 300 mosmol/kgH(2)O of NaCl by urea in cells adapted to 600 mosmol/kgH(2)O resulted in marked decrement in Na-K-ATPase and failure to maintain the cell line. Replacement of NaCl for urea in cells adapted to 900 mosmol/kgH(2)O did not alter either Na-K-ATPase expression, or the viability of the cells. The in vivo modulation of Na-K-ATPase was studied in the renal papilla of water-deprived mice (urinary osmolality 2,900 mosmol/ kgH(2)O), compared with that of mice drinking dextrose in water (550 mosmol/ kgH(2)O). Increased water intake was associated with a similar to 30% decrement in Na-K-ATPase expression (P< 0.02, n = 6), suggesting that this enzyme is osmoregulated in vivo. We conclude that whereas MAP kinases play a role in the response to acute changes in tonicity, they are not central to the chronic adaptive response. Rather, in this setting there is upregulation of other osmoprotective proteins, among which Na-K-ATPase appears to be an important component of the adaptive process.