AJP - Renal Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (May 17, 2005). doi:10.1152/ajprenal.00448.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/4/F803    most recent
00448.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cai, Q.
Right arrow Articles by Burg, M. B
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cai, Q.
Right arrow Articles by Burg, M. B
Submitted on December 13, 2004
Accepted on April 6, 2005

High NaCl increases TonEBP/OREBP mRNA and protein by stabilizing its mRNA

Qi Cai1, Joan D Ferraris1, and Maurice B Burg1*

1 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, Bethesda, MD, USA

* To whom correspondence should be addressed. E-mail: maurice_burg{at}nih.gov.

Hypertonicity increases mRNA and protein abundance of the transcription factor TonEBP/OREBP, contributing to increased transcription of downstream osmoprotective genes. Previously, this was attributed to increased transcription of TonEBP/OREBP since no change was found in its mRNA stability. However, there is no direct evidence for increased transcription, and the 3'-UTR of TonEBP/OREBP contains numerous adenylate/uridylate-rich elements, which can modulate RNA stability. Therefore, we have reinvestigated the effect of hypertonicity on TonEBP/OREBP mRNA stability. We find that, in mIMCD3 cells, raising osmolality from 300 to 500 mosmol/kg by adding NaCl increases TonEBP/OREBP mRNA to a peak of 2.3 fold after 4 hours, followed by a decline. TonEBP/OREBP protein increases to a sustained peak of 3.0 fold at 8 hours. To determine the stability of TonEBP/OREBP mRNA, we measured the rate of its decrease after inhibiting transcription with actinomycin, finding that it is stabilized for 6 hours after adding NaCl. This stabilization is sufficient to explain the increase in mRNA without any change in transcription. To investigate how hypertonicity stabilizes TonEBP/OREBP mRNA, we tested luciferase reporters containing parts of the TonEBP/OREBP mRNA UTR. Inclusion of both the 5'- and 3'-UTR increases reporter activity, consistent with mRNA stabilization. Surprisingly, however, it is the 5'-UTR that stabilizes; the 3'-UTR, by itself, decreases reporter activity. Conclusions: 1) Hypertonicity stabilizes TonEBP/OREBP mRNA, contributing to its increase. 2) Stabilization depends on the presence of the 5'-UTR.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
S. R. Tew, M. J. Peffers, T. R. McKay, E. T. Lowe, W. S. Khan, T. E. Hardingham, and P. D. Clegg
Hyperosmolarity regulates SOX9 mRNA posttranscriptionally in human articular chondrocytes
Am J Physiol Cell Physiol, October 1, 2009; 297(4): C898 - C906.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
M. S. Kwon, S. W. Lim, and H. M. Kwon
Hypertonic Stress in the Kidney: A Necessary Evil
Physiology, June 1, 2009; 24(3): 186 - 191.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
C. Kuper, D. Steinert, M.-L. Fraek, F.-X. Beck, and W. Neuhofer
EGF receptor signaling is involved in expression of osmoprotective TonEBP target gene aldose reductase under hypertonic conditions
Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1100 - F1108.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
E. K. Hoffmann, I. H. Lambert, and S. F. Pedersen
Physiology of Cell Volume Regulation in Vertebrates
Physiol Rev, January 1, 2009; 89(1): 193 - 277.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
Y.-M. Kim, W.-Y. Kim, H.-W. Lee, J. Kim, H. M. Kwon, J. D. Klein, J. M. Sands, and D. Kim
Urea and NaCl regulate UT-A1 urea transporter in opposing directions via TonEBP pathway during osmotic diuresis
Am J Physiol Renal Physiol, January 1, 2009; 296(1): F67 - F77.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
T. Rodgaard, K. Schou, M. B. Friis, and E. K. Hoffmann
Does the intracellular ionic concentration or the cell water content (cell volume) determine the activity of TonEBP in NIH3T3 cells?
Am J Physiol Cell Physiol, December 1, 2008; 295(6): C1528 - C1534.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
P. Bissonnette, K. Lahjouji, M. J. Coady, and J.-Y. Lapointe
Effects of hyperosmolarity on the Na+-myo-inositol cotransporter SMIT2 stably transfected in the Madin-Darby canine kidney cell line
Am J Physiol Cell Physiol, September 1, 2008; 295(3): C791 - C799.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.