Document Detail


Glutamine synthetase expression in muscle is regulated by transcriptional and posttranscriptional mechanisms.
MedLine Citation:
PMID:  10362628     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Skeletal muscle exports glutamine (Gln) and increases the expression of the enzyme glutamine synthetase (GS) in response to physiological stress. Acute stress or direct glucocorticoid administration raises muscle GS mRNA levels dramatically without a parallel increase in GS protein levels. In the lung, this discrepancy is caused by feedback destabilization of the GS protein by its product Gln. It was hypothesized that muscle GS protein levels increase during stress only when the intracellular Gln pool has been depleted. Adult male rats were injected with the glucocorticoid hormone dexamethasone (DEX) to mimic the acute stress response and with the GS inhibitor methionine sulfoximine (MSO) to deplete muscle Gln stores. DEX increased GS mRNA levels by 2.8-fold but increased GS protein levels by an average of only 40%. MSO diminished muscle GLN levels by 68% and caused GS protein levels to rise in accordance with GS mRNA. Chronic stress was mimicked using 6 days of MSO treatment, which produced anorexia, 23% loss of body weight, and 64% decrease in muscle Gln levels, as well as pronounced increases in both muscle GS mRNA (26-fold) and protein levels (35-fold) without elevation of plasma glucocorticoid levels. Calorie-restricted pair-fed animals exhibited lesser increases in muscle GS mRNA (8-fold) and protein levels (5-fold) without a decline in muscle Gln content. Thus regulation of GS expression in both acute and chronic stress involved both transcriptional and posttranscriptional mechanisms, perhaps affected by muscle Gln content.
Authors:
B I Labow; W W Souba; S F Abcouwer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  276     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-07-29     Completed Date:  1999-07-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  E1136-45     Citation Subset:  IM    
Affiliation:
Surgical Oncology Research Laboratories, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, Massachusetts 02114, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dexamethasone / pharmacology
Enzyme Inhibitors / pharmacology
Glucocorticoids / pharmacology
Glutamate-Ammonia Ligase / antagonists & inhibitors,  genetics,  metabolism*
Glutamine / metabolism
Male
Methionine Sulfoximine / pharmacology
Muscle, Skeletal / enzymology*,  metabolism
Protein Processing, Post-Translational / physiology*
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Transcription, Genetic / physiology*
Grant Support
ID/Acronym/Agency:
R01-HL-44986/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Glucocorticoids; 0/RNA, Messenger; 1982-67-8/Methionine Sulfoximine; 50-02-2/Dexamethasone; 56-85-9/Glutamine; EC 6.3.1.2/Glutamate-Ammonia Ligase

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


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