Document Detail

Ceramide down-regulates System A amino acid transport and protein synthesis in rat skeletal muscle cells.
MedLine Citation:
PMID:  15611152     Owner:  NLM     Status:  MEDLINE    
Skeletal muscle is a major insulin target tissue and has a prominent role in the control of body amino acid economy, being the principal store of free and protein-bound amino acids and a dominant locus for amino acid metabolism. Interplay between diverse stimuli (e.g., hormonal/nutritional/mechanical) modulates muscle insulin action to serve physiological need through the action of factors such as intramuscular signaling molecules. Ceramide, a product of sphingolipid metabolism and cytokine signaling, has a potent contra-insulin action with respect to the transport and deposition of glucose in skeletal muscle, although ceramide effects on muscle amino acid turnover have not previously been documented. Here, membrane permeant C2-ceramide is shown to attenuate the basal and insulin-stimulated activity of the Na+-dependent System A amino acid transporter in rat muscle cells (L6 myotubes) by depletion of the plasma membrane abundance of SNAT2 (a System A isoform). Concomitant with transporter down-regulation, ceramide diminished both intramyocellular amino acid abundance and the phosphorylation of translation regulators lying downstream of mTOR. The physiological outcome of ceramide signaling in this instance is a marked reduction in cellular protein synthesis, a result that is likely to represent an important component of the processes leading to muscle wasting in catabolic conditions.
Russell Hyde; Eric Hajduch; Darren J Powell; Peter M Taylor; Harinder S Hundal
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-12-20
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  19     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-04     Completed Date:  2005-10-25     Revised Date:  2014-10-14    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  461-3     Citation Subset:  IM    
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MeSH Terms
Amino Acid Transport System A / antagonists & inhibitors*,  drug effects,  metabolism
Amino Acid Transport Systems / analysis,  antagonists & inhibitors,  physiology
Amino Acids / analysis,  metabolism
Cell Line
Cell Membrane / chemistry
Ceramides / pharmacology*
Glucose / metabolism
Muscle Cells / drug effects,  metabolism*
Muscle Fibers, Skeletal / drug effects,  metabolism
Muscle Proteins / biosynthesis*
Muscle, Skeletal / chemistry,  drug effects,  metabolism*
Protein Kinases / metabolism
Signal Transduction / drug effects
TOR Serine-Threonine Kinases
Grant Support
C19477//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Amino Acid Transport System A; 0/Amino Acid Transport Systems; 0/Amino Acids; 0/Ceramides; 0/Muscle Proteins; 0/SNAT2 protein, rat; EC 2.7.-/Protein Kinases; EC Serine-Threonine Kinases; EC protein, rat; IY9XDZ35W2/Glucose

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

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