| Ceramide down-regulates System A amino acid transport and protein synthesis in rat skeletal muscle cells. | |
| | |
MedLine Citation:
|
PMID: 15611152 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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: 2012-02-15 |
Medline Journal Info:
|
Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
|
Languages: eng Pagination: 461-3 Citation Subset: IM |
Affiliation:
|
Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Transport System A
/
antagonists & inhibitors*,
drug effects,
metabolism Amino Acid Transport Systems / analysis, antagonists & inhibitors, physiology Amino Acids / analysis, metabolism Animals 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 Rats Signal Transduction / drug effects TOR Serine-Threonine Kinases |
| Chemical | |
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; 50-99-7/Glucose; EC 2.7.-/Protein Kinases; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Spontaneous osteoclast formation from peripheral blood mononuclear cells in postmenopausal osteoporo...
Next Document: Role for nitrosative stress in diabetic neuropathy: evidence from studies with a peroxynitrite decom...