AJP - Renal Physiology, Vol 271, Issue 2 340-F346, Copyright © 1996 by American Physiological Society

ARTICLES

Promoter elements that mediate the pH response of PCK mRNA in LLC-PK1-F+ cells

T. Holcomb, W. Liu, R. Snyder, R. Shapiro and N. P. Curthoys
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins 80523, USA.

The onset of metabolic acidosis causes an increased transcription of the renal phosphoenolpyruvate carboxykinase (PCK) gene. When transgenic mice carrying a bovine growth hormone (bGH) gene driven by the -460 to +73 segment of the PCK promoter were made chronically acidotic, the bGH mRNA was increased twofold after 4 days. Confluent and well-differentiated cultures of LLC-PK1-F+ cells exhibit a 2.5-fold increase in PCK mRNA when transferred to acidic media (pH 6.9, 10 mM HCO3-) for 16 h. Confluent cultures transfected with PCK-490 CAT exhibit an increase (3.5-fold) in chloramphenicol acetyltransferase (CAT) activity when shifted to acidic medium for 48 h. Mutation or deletion of the P2 element causes a four- to fivefold decrease in basal CAT activity but does not affect the pH response. In contrast, mutations of the P3(II) element or the CRE-1 cAMP-response element have little effect on basal activity but cause a 50% decrease in the pH response. Other deletions or mutations have little effect on either activity. Thus changes in the activity or levels of the protein(s) in the renal proximal tubule that binds to the P3(II) and CRE-1 elements may mediate increased transcription of the PCK gene during metabolic acidosis.

This article has been cited by other articles:

				H. Christou, N. Bailey, M. S. Kluger, S. A. Mitsialis, and S. Kourembanas Extracellular acidosis induces heme oxygenase-1 expression in vascular smooth muscle cells Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2647 - H2652. [Abstract] [Full Text] [PDF]

				C. Terminella, K. Tollefson, J. Kroczynski, J. Pelli, and M. Cutaia Inhibition of apoptosis in pulmonary endothelial cells by altered pH, mitochondrial function, and ATP supply Am J Physiol Lung Cell Mol Physiol, December 1, 2002; 283(6): L1291 - L1302. [Abstract] [Full Text] [PDF]

				E. Feifel, P. Obexer, M. Andratsch, S. Euler, L. Taylor, A. Tang, Y. Wei, H. Schramek, N. P. Curthoys, and G. Gstraunthaler p38 MAPK mediates acid-induced transcription of PEPCK in LLC-PK1-FBPase+ cells Am J Physiol Renal Physiol, October 1, 2002; 283(4): F678 - F688. [Abstract] [Full Text] [PDF]

				N. P. Curthoys and G. Gstraunthaler Mechanism of increased renal gene expression during metabolic acidosis Am J Physiol Renal Physiol, September 1, 2001; 281(3): F381 - F390. [Abstract] [Full Text] [PDF]

				X. Wang, J. M. Chinsky, P. A. Costeas, and S. R. Price Acidification and glucocorticoids independently regulate branched-chain {alpha}-ketoacid dehydrogenase subunit genes Am J Physiol Cell Physiol, May 1, 2001; 280(5): C1176 - C1183. [Abstract] [Full Text] [PDF]

				O. F. Laterza, L. Taylor, S. Unnithan, L. Nguyen, and N. P. Curthoys Mapping and functional analysis of an instability element in phosphoenolpyruvate carboxykinase mRNA Am J Physiol Renal Physiol, November 1, 2000; 279(5): F866 - F873. [Abstract] [Full Text] [PDF]

				G. Gstraunthaler, T. Holcomb, E. Feifel, W. Liu, N. Spitaler, and N. P. Curthoys Differential expression and acid-base regulation of glutaminase mRNAs in gluconeogenic LLC-PK1-FBPase+ cells Am J Physiol Renal Physiol, February 1, 2000; 278(2): F227 - F237. [Abstract] [Full Text] [PDF]

				W. Liu, E. Feifel, T. Holcomb, X. Liu, N. Spitaler, G. Gstraunthaler, and N. P. Curthoys PMA and staurosporine affect expression of the PCK gene in LLC-PK1-F+ cells Am J Physiol Renal Physiol, September 1, 1998; 275(3): F361 - F369. [Abstract] [Full Text] [PDF]

				B. M. Christensen, D. Marples, U. B. Jensen, J. Frokiaer, D. Sheikh-Hamad, M. Knepper, and S. Nielsen Acute effects of vasopressin V2-receptor antagonist on kidney AQP2 expression and subcellular distribution Am J Physiol Renal Physiol, August 1, 1998; 275(2): F285 - F297. [Abstract] [Full Text] [PDF]

				O. F. Laterza, W. R. Hansen, L. Taylor, and N. P. Curthoys Identification of an mRNA-binding Protein and the Specific Elements That May Mediate the pH-responsive Induction of Renal Glutaminase mRNA J. Biol. Chem., September 5, 1997; 272(36): 22481 - 22488. [Abstract] [Full Text] [PDF]