AJP - Cell Physiology, Vol 256, Issue 3 C614-C620, Copyright © 1989 by American Physiological Society

ARTICLES

Signal for induction of aldose reductase in renal medullary cells by high external NaCl

S. Uchida, A. Garcia-Perez, H. Murphy and M. Burg
National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.

GRB-PAP1 is a continuous line of epithelial cells derived from rabbit renal inner medulla. These cells accumulate large amounts of sorbitol when extracellular NaCl concentration is elevated. The accumulation involves an increase in aldose reductase, an enzyme that catalyzes production of sorbitol from glucose. The purpose of the present studies was to investigate the mechanism by which high NaCl triggers an increase in aldose reductase activity. When NaCl was added to increase medium osmolality from 300 to 500 mosmol/kg, enzyme activity began to increase after 12-24 h, was half-maximal in 2 days, and was maximal by 4 days. To test the effect of other solutes, medium osmolality was increased to 500 mosmol/kg by adding raffinose, urea, or glycerol. Raffinose increased aldose reductase activity as much as NaCl did. In contrast, neither urea nor glycerol affected the enzyme activity. NaCl and raffinose caused a sustained decrease in cell water content and an increase in cell sodium and potassium concentration, but urea did not. In some experiments, ouabain was added either with or without an increase in osmolality. Taking into account all of the experiments, with and without ouabain, we found that aldose reductase activity did not correlate with either cell sodium concentration or cell water content alone. It did correlate, however, with cell potassium concentration and even more strongly with the sum of cell sodium plus potassium concentration. We conclude that the signal by which hyperosmolality triggers an increase in aldose reductase activity most likely involves an increase in intracellular ionic strength.

This article has been cited by other articles:

				M. B. Burg, J. D. Ferraris, and N. I. Dmitrieva Cellular Response to Hyperosmotic Stresses Physiol Rev, October 1, 2007; 87(4): 1441 - 1474. [Abstract] [Full Text] [PDF]

				N. I. Dmitrieva, M. B. Burg, and J. D. Ferraris DNA damage and osmotic regulation in the kidney Am J Physiol Renal Physiol, July 1, 2005; 289(1): F2 - F7. [Abstract] [Full Text] [PDF]

				K. Strange Cellular volume homeostasis Advan Physiol Educ, December 1, 2004; 28(4): 155 - 159. [Abstract] [Full Text] [PDF]

				D. Sheikh-Hamad and M. C. Gustin MAP kinases and the adaptive response to hypertonicity: functional preservation from yeast to mammals Am J Physiol Renal Physiol, December 1, 2004; 287(6): F1102 - F1110. [Abstract] [Full Text] [PDF]

				W. Neuhofer, S. K. Woo, K. Y. Na, R. Grunbein, W. K. Park, O. Nahm, F.-X. Beck, and H. M. Kwon Regulation of TonEBP transcriptional activator in MDCK cells following changes in ambient tonicity Am J Physiol Cell Physiol, December 1, 2002; 283(6): C1604 - C1611. [Abstract] [Full Text] [PDF]

				D. Sheikh-Hamad, K. Youker, L. D. Truong, S. Nielsen, and M. L. Entman Osmotically relevant membrane signaling complex: association between HB-EGF, beta 1-integrin, and CD9 in mTAL Am J Physiol Cell Physiol, July 1, 2000; 279(1): C136 - C146. [Abstract] [Full Text] [PDF]

				Y. Miyata, S. Muto, S. Yanagiba, and Y. Asano Extracellular Cl- modulates shrinkage-induced activation of Na+/H+ exchanger in rat mesangial cells Am J Physiol Cell Physiol, June 1, 2000; 278(6): C1218 - C1229. [Abstract] [Full Text] [PDF]

				S. K. Woo, S. C. Dahl, J. S. Handler, and H. M. Kwon Bidirectional regulation of tonicity-responsive enhancer binding protein in response to changes in tonicity Am J Physiol Renal Physiol, June 1, 2000; 278(6): F1006 - F1012. [Abstract] [Full Text] [PDF]

				D. Sheikh-Hamad, D. Rouse, and Y. Yang Regulation of stanniocalcin in MDCK cells by hypertonicity and extracellular calcium Am J Physiol Renal Physiol, March 1, 2000; 278(3): F417 - F424. [Abstract] [Full Text] [PDF]

				W. C. O'Neill Physiological significance of volume-regulatory transporters Am J Physiol Cell Physiol, May 1, 1999; 276(5): C995 - C1011. [Abstract] [Full Text] [PDF]

				J. S. Rim, M. G. Atta, S. C. Dahl, G. T. Berry, J. S. Handler, and H. M. Kwon Transcription of the Sodium/myo-Inositol Cotransporter Gene Is Regulated by Multiple Tonicity-responsive Enhancers Spread over 50 Kilobase Pairs in the 5'-Flanking Region J. Biol. Chem., August 7, 1998; 273(32): 20615 - 20621. [Abstract] [Full Text] [PDF]

				B. C. Santos, A. Chevaile, R. Kojima, and S. R. Gullans Characterization of the Hsp110/SSE gene family response to hyperosmolality and other stresses Am J Physiol Renal Physiol, June 1, 1998; 274(6): F1054 - F1061. [Abstract] [Full Text] [PDF]

				D. Sheikh-Hamad, J. Di Mari, W. N. Suki, R. Safirstein, B. A. Watts III, and D. Rouse p38 Kinase Activity Is Essential for Osmotic Induction of mRNAs for HSP70 and Transporter for Organic Solute Betaine in Madin-Darby Canine Kidney Cells J. Biol. Chem., January 16, 1998; 273(3): 1832 - 1837. [Abstract] [Full Text] [PDF]

				F. LANG, G. L. BUSCH, M. RITTER, H. VOLKL, S. WALDEGGER, E. GULBINS, and D. HAUSSINGER Functional Significance of Cell Volume Regulatory Mechanisms Physiol Rev, January 1, 1998; 78(1): 247 - 306. [Abstract] [Full Text] [PDF]

				B. C. B. Ko, B. Ruepp, K. M. Bohren, K. H. Gabbay, and S. S. M. Chung Identification and Characterization of Multiple Osmotic Response Sequences in the Human Aldose Reductase Gene J. Biol. Chem., June 27, 1997; 272(26): 16431 - 16437. [Abstract] [Full Text] [PDF]

				J. D. Ferraris, C. K. Williams, K.-Y. Jung, J. J. Bedford, M. B. Burg, and A. Garcia-Perez ORE, a Eukaryotic Minimal Essential Osmotic Response Element. THE ALDOSE REDUCTASE GENE IN HYPEROSMOTIC STRESS J. Biol. Chem., August 2, 1996; 271(31): 18318 - 18321. [Abstract] [Full Text] [PDF]