Document Detail


Synthesis of the Na-K-ATPase gamma-subunit is regulated at both the transcriptional and translational levels in IMCD3 cells.
MedLine Citation:
PMID:  15383396     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that hypertonicity-mediated upregulation of the gamma-subunit of Na-K-ATPase is dependent on both the JNK and the PI3 kinase pathways. The present experiments were undertaken to explore the mechanisms whereby these pathways regulate the expression of the gamma-subunit in inner medullary collecting duct cells (IMCD3). Inhibition of JNK with SP-600125 (20 muM), a concentration that causes an approximately 95% inhibition of hypertonicity-stimulated JNK activation, markedly decreased the amount of the gamma-subunit in response to 550 mosmol/kgH(2)O for 48 h. This was accompanied by a parallel decrease in the gamma-subunit mRNA. The rate at which the gamma-subunit mRNA decreased was unaffected by actinomycin D. In contrast, inhibition of PI3 kinase with LY-294002 results in a marked decrease in the amount of gamma-subunit protein but without alteration in gamma-subunit message. The rate at which the gamma-subunit protein decreased was unaffected by cyclohexamide. Transfection of IMCD3 cells with a gamma-subunit construct results in the expression of both gamma-subunit message and protein. However, in cortical collecting duct cells (M1 cells) such transfection resulted in expression of only the message and not the protein. We conclude that JNK regulates the gamma-subunit at the transcriptional level while PI3 kinase regulates gamma-subunit expression at the translational level. There is also posttranscriptional cell specificity in the expression of the gamma -subunit of Na-K-ATPase.
Authors:
Juan M Capasso; Christopher J Rivard; Tomas Berl
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-09-21
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  288     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-07     Completed Date:  2005-03-04     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F76-81     Citation Subset:  IM    
Affiliation:
University of Colorado Health Sciences Center, 4200 E. 9th Ave., Mail Stop C-281, Denver, CO 80262, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anthracenes / pharmacology
Cell Line
Chromones / pharmacology
Down-Regulation
Gene Expression Regulation, Enzymologic
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Kidney Cortex / cytology,  enzymology
Kidney Medulla / drug effects,  enzymology*
Kidney Tubules, Collecting / drug effects,  enzymology
MAP Kinase Kinase 4
Mice
Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors,  metabolism
Morpholines / pharmacology
Phosphatidylinositol 3-Kinases / antagonists & inhibitors
Protein Biosynthesis / physiology*
Signal Transduction / physiology
Sodium-Potassium-Exchanging ATPase / biosynthesis*
Transcription, Genetic / physiology*
Grant Support
ID/Acronym/Agency:
DK-19928/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Anthracenes; 0/Chromones; 0/Morpholines; 0/anthra(1,9-cd)pyrazol-6(2H)-one; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.12.2/MAP Kinase Kinase 4; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases; EC 3.6.1.-/Fxyd2 protein, mouse; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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