Ferraris J D, Burg M B, Williams C K, Peters E M, García-Pérez A
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Am J Physiol. 1996 Feb;270(2 Pt 1):C650-4. doi: 10.1152/ajpcell.1996.270.2.C650.
Cells generally adapt to long-term hyperosmolality by accumulating compatible organic osmolytes, thereby helping to normalize both volume and intracellular inorganic ion concentration. When organic osmolytes are accumulated, as in renal inner medullary cells, it is the sum of their concentrations that is theoretically important. In effect, when one organic osmolyte rises, the others generally fall to maintain their sum approximately constant. The present study addresses the mechanism controlling betaine accumulation. Hypertonicity induces accumulation of betaine, sorbitol, inositol, and other organic osmolytes in PAP-HT25 cells, a line derived from rabbit renal papilla. Hypertonicity increases the betaine transporter expression in these cells. To obtain a specific probe for betaine transporter mRNA, we cloned from PAP-HT25 cells a cDNA that encodes the full protein. We then examined the effect of betaine, sorbitol, and inositol on betaine transporter mRNA abundance. Increased accumulation of any of these three organic osmolytes reduces betaine transporter mRNA. We previously observed similar results for aldose reductase, the enzyme responsible for osmotically regulated sorbitol accumulation. We conclude that the accumulation of organic osmolytes regulates betaine transporter gene expression. Because the aldose reductase gene is controlled in a similar fashion, we surmise that the two genes share a common signal for induction.
细胞通常通过积累相容性有机渗透溶质来适应长期的高渗状态，从而有助于使细胞体积和细胞内无机离子浓度恢复正常。当有机渗透溶质积累时，如在肾髓质内层细胞中，理论上重要的是它们的浓度总和。实际上，当一种有机渗透溶质增加时，其他溶质通常会减少，以保持它们的总和大致恒定。本研究探讨了控制甜菜碱积累的机制。高渗诱导甜菜碱、山梨醇、肌醇和其他有机渗透溶质在PAP-HT25细胞（一种源自兔肾乳头的细胞系）中积累。高渗增加了这些细胞中甜菜碱转运蛋白的表达。为了获得甜菜碱转运蛋白mRNA的特异性探针，我们从PAP-HT25细胞中克隆了一个编码完整蛋白的cDNA。然后我们检测了甜菜碱、山梨醇和肌醇对甜菜碱转运蛋白mRNA丰度的影响。这三种有机渗透溶质中任何一种的积累增加都会降低甜菜碱转运蛋白mRNA的水平。我们之前观察到醛糖还原酶（负责渗透压调节的山梨醇积累的酶）也有类似的结果。我们得出结论，有机渗透溶质的积累调节甜菜碱转运蛋白基因的表达。由于醛糖还原酶基因是以类似的方式被调控的，我们推测这两个基因共享一个共同的诱导信号。
