title: Attenuation of autophagic-proteolysis in C2C12 cells by saccharopine.
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.
authors: Department of Bioresource Science, The United Graduate School of Agricultural Science, Iwate University, Morioka, Iwate, 020-8550, Japan.
authors: Tomonori
authors: T
authors: Sato
authors: Department of Biological Chemistry and Food Science, Graduate School of Agriculture, Iwate University, Morioka, Iwate, 020-8550, Japan. yito@iwate-u.ac.jp.
authors: Yoshiaki
authors: Y
authors: Ito
authors: Department of Biological Chemistry and Food Science, Graduate School of Agriculture, Iwate University, Morioka, Iwate, 020-8550, Japan.
authors: Takashi
authors: T
authors: Nagasawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D039642:Eukaryotic Initiation Factors; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008762:Methylhistidines / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; C480860:Map1lc3b protein, mouse; D008762:Methylhistidines; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D008239:Lysine; C028118:3-methylhistidine; C100169:saccharopine
keywords: Akt; Autophagy; Lysine; Saccharopine; Sarcopenia; mTOR