Abstract
Muscle wasting impairs physical function and leads people to a bedridden state. We previously demonstrated that lysine (Lys) suppresses autophagic-proteolysis through the Akt pathway. However, the effect of metabolites of Lys on proteolysis is unclear. In this study, we investigated the effect of saccharopine (Sac), a metabolite of Lys, on proteolysis in C2C12 cells. When C2C12 myotubes were incubated in serum-free medium containing Sac, the rate of proteolysis, which was evaluated by 3-methylhistidine released from C2C12 myotubes, and autophagy activity, which was assessed by amount of light chain 3-II, were suppressed. Sac stimulated Akt and mammalian target of rapamycin signaling, which was evaluated from eIF4E-binding protein 1 phosphorylation. The suppressive effects of Sac on proteolysis and autophagy were completely abolished by an Akt inhibitor. Therefore, we concluded that Sac suppresses autophagic-proteolysis through Akt as with Lys.
Keywords:
Akt; Autophagy; Lysine; Saccharopine; Sarcopenia; mTOR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Autophagy / drug effects*
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Carrier Proteins / metabolism
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Cell Cycle Proteins
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Cell Line
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Eukaryotic Initiation Factors
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Kinetics
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Lysine / analogs & derivatives*
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Lysine / pharmacology
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Methylhistidines / metabolism
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Mice
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Microtubule-Associated Proteins / metabolism
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Muscle Fibers, Skeletal / drug effects*
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Muscle Fibers, Skeletal / enzymology
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Muscle Fibers, Skeletal / pathology
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Muscular Atrophy / drug therapy*
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Muscular Atrophy / enzymology
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Muscular Atrophy / pathology
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Kinase Inhibitors / pharmacology
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Proteolysis / drug effects*
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction / drug effects
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TOR Serine-Threonine Kinases / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cell Cycle Proteins
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Eif4ebp1 protein, mouse
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Eukaryotic Initiation Factors
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Map1lc3b protein, mouse
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Methylhistidines
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Microtubule-Associated Proteins
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Phosphoproteins
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Protein Kinase Inhibitors
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mTOR protein, mouse
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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Lysine
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3-methylhistidine
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saccharopine