Document Detail


Glucocorticoids modulate amino acid-induced translation initiation in human skeletal muscle.
MedLine Citation:
PMID:  15039148     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Amino acids are unique anabolic agents in that they nutritively signal to mRNA translation initiation and serve as substrates for protein synthesis in skeletal muscle. Glucocorticoid excess antagonizes the anabolic action of amino acids on protein synthesis in laboratory animals. To examine whether excessive glucocorticoids modulate mixed amino acid-signaled translation initiation in human skeletal muscle, we infused an amino acid mixture (10% Travasol) systemically to 16 young healthy male volunteers for 6 h in the absence (n = 8) or presence (n = 8) of glucocorticoid excess (dexamethasone 2 mg orally every 6 h for 3 days). Vastus lateralis muscles were biopsied before and after amino acid infusion, and the phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1), ribosomal protein S6 kinase (p70(S6K)), and eIF2alpha and the guanine nucleotide exchange activity of eIF2B were measured. Systemic infusion of mixed amino acids significantly stimulated the phosphorylation of 4E-BP1 (P < 0.04) and p70(S6K) (P < 0.001) and the dephosphorylation of eIF2alpha (P < 0.003) in the control group. Dexamethasone treatment did not alter the basal phosphorylation state of 4E-BP1, p70(S6K), or eIF2alpha; however, it abrogated the stimulatory effect of amino acid infusion on the phosphorylation of 4E-BP1 (P = 0.31) without affecting amino acid-induced phosphorylation of p70(S6K) (P = 0.002) or dephosphorylation of eIF2alpha (P = 0.003). Neither amino acid nor dexamethasone treatment altered the guanine nucleotide exchange activity of eIF2B. We conclude that changes of amino acid concentrations within the physiological range stimulate mRNA translation by enhancing the binding of mRNA to the 43S preinitiation complex, and the activity of p70(S6K) and glucocorticoid excess blocks the former action in vivo in human skeletal muscle.
Authors:
Zhenqi Liu; Guolian Li; Scot R Kimball; Linda A Jahn; Eugene J Barrett
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.     Date:  2004-03-23
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  287     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-23     Completed Date:  2004-08-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E275-81     Citation Subset:  IM    
Affiliation:
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA 22908-1410, USA. zl3e@virginia.edu
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing
Administration, Oral
Adult
Amino Acids / metabolism*
Blood Glucose / metabolism
Carrier Proteins / metabolism
Dexamethasone / administration & dosage*,  metabolism
Drug Administration Schedule
Eukaryotic Initiation Factor-2 / metabolism
Eukaryotic Initiation Factor-2B / metabolism
Glucocorticoids / administration & dosage*,  metabolism
Humans
Insulin / blood
Male
Muscle Proteins / metabolism*
Muscle, Skeletal / metabolism*
Phosphoproteins / metabolism
Phosphorylation
Protein Biosynthesis / physiology*
Reference Values
Ribosomal Protein S6 Kinases, 70-kDa / metabolism
Grant Support
ID/Acronym/Agency:
DK-15658/DK/NIDDK NIH HHS; DK-38578/DK/NIDDK NIH HHS; DK-54058/DK/NIDDK NIH HHS; RR-0847/RR/NCRR NIH HHS; RR-15540/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Amino Acids; 0/Blood Glucose; 0/Carrier Proteins; 0/EIF4EBP1 protein, human; 0/Eukaryotic Initiation Factor-2; 0/Eukaryotic Initiation Factor-2B; 0/Glucocorticoids; 0/Muscle Proteins; 0/Phosphoproteins; 11061-68-0/Insulin; 50-02-2/Dexamethasone; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa

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


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