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Ceramide down‐regulates System A amino acid transport and protein synthesis in rat skeletal muscle cells
Author(s) -
Hyde Russell,
Hajduch Eric,
Powell Darren J.,
Taylor Peter M.,
Hundal Harinder S.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2284fje
Subject(s) - ceramide , skeletal muscle , sphingolipid , biochemistry , biology , myogenesis , microbiology and biotechnology , insulin , catabolism , signal transduction , insulin receptor , myocyte , medicine , chemistry , endocrinology , metabolism , insulin resistance , apoptosis
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 C 2 ‐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.