title: Lysine suppresses myofibrillar protein degradation by regulating the autophagic-lysosomal system through phosphorylation of Akt in C2C12 cells.
abstract: The prevention of muscle wasting is important for maintaining quality of life, since loss of muscle mass can lead to a bedridden state and decreased resistance to diseases. The prevention of muscle wasting requires an increase in protein synthesis and a decrease in protein degradation in skeletal muscle. We previously showed that lysine (Lys) markedly suppressed myofibrillar protein degradation by inhibiting the autophagic-lysosomal system via the mammalian target of rapamycin (mTOR) and other signal molecules in C2C12 cells. In this study, we investigated the involvement of Akt and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), two regulators of autophagy, on the suppressive effects of Lys on myofibrillar protein degradation in C2C12 cells. Lys induced the phosphorylation of Akt, but the suppressive effects of Lys on myofibrillar protein degradation and autophagy were completely abolished in the presence of Akt1/2 kinase inhibitor (Akti). Lys suppressed the phosphorylation of AMPK, but this effect was also abolished by Akti. On the other hand, AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR) did not affect either Akt activity or the autophagic-lysosomal system in C2C12 cells treated with Lys. These results indicate that regulation of AMPK activity is not essential for the regulation of autophagy by Lys. Taken together, our results show that Lys suppresses myofibrillar protein degradation by the autophagic-lysosomal system through the phosphorylation of Akt in C2C12 cells.
authors.affiliation: Department of Bioresources Science, The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Iwate 020-8550 Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Biological Chemistry and Food Science, Graduate School of Agriculture, Iwate University, Morioka, Iwate 020-8550 Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Biological Chemistry and Food Science, Graduate School of Agriculture, Iwate University, Morioka, Iwate 020-8550 Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
keywords: AMPK; Akt; C2C12; Lysine; Proteolysis