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.

NAD(P)H‐Dependent Dehydrogenases for the Asymmetric Reductive Amination of Ketones: Structure, Mechanism, Evolution and Application

“…Opine dehydrogenases (OpDHs, E.C.1.5.1.28) are a class of AADHs that catalyse the reversible reductive coupling of amino acid and keto acids to form N ‐derivatised amino acids called opines. The model reaction catalysed by these enzymes in the BRENDA database (http://www.brenda-enzymes.org) is the NADH‐dependent coupling of aminopentanoic acid 15 and pyruvate 16 into (2 S )‐2‐{[1‐( R )‐carboxyethyl]amino}pentanoate 17 (Scheme ).…”

Analysis of Phytoconstituent Profile of Fenugreek – Trigonella Foenuem-Graecum L. – Seed Extracts

“…Lysine is catabolized in developing plant tissues through the saccharopine pathway, and have been shown to be involved in the development of maize seed and stress responses [53]. In the case of mammalian myotubes, saccharopine was shown to stimulate Akt and mTOR signalling that has suppressed autophagic-proteolysis, and might reduce muscle wasting [54].…”

Regulatory effects of the L-lysine metabolites, L-2-aminoadipic acid and L-pipecolic acid, on protein turnover in C2C12 myotubes

“…9,10) Lys is catabolized via the saccharopine (Sac) and pipecolic acid (Pip) pathways ( Fig. 1), 11) and Sac and Pip are catabolized to L-2aminoadipic acid (2-AA). 11) We previously showed that Sac, one of metabolites of Lys, suppresses autophagic proteolysis through a similar pathway as Lys.…”

“…1), 11) and Sac and Pip are catabolized to L-2aminoadipic acid (2-AA). 11) We previously showed that Sac, one of metabolites of Lys, suppresses autophagic proteolysis through a similar pathway as Lys. 11) However, it is unknown whether other metabolites of Lys, Pip which is a major Lys metabolite produced in the Pip pathway and 2-AA which is a common metabolite in the Sac and Pip pathways, regulate protein turnover similarly to Sac.…”