Approaches for Maintaining and Enhancing of Skeletal Muscle Mass by Starvation-Induced Autophagy

Abstract

Effect of glucose starvation-induced proteolysis on protein translation initiation in response to glucose restoration was examined in C2C12 myotubes. C2C12 cells were cultured in differentiation medium （DMEM containing 2% horse serum and 25 mM glucose） for 4 days. Differentiated C2C12 cells were further cultured in differentiation medium （HG） or in differentiation medium without glucose （NG） for 24h. Glucose （final concentration at 5.5 mM） was added to the both groups, and cells were collected after 30 min of incubation. The phosphorylation level of p70 S6 kinase （p70S6K）， which is the marker for protein translation initiation, was significantly decreased by glucose starvation for 24h. Addition of glucose markedly increased the phosphorylation of p70S6K only in NG group and this phosphorylation level was significantly greater than in HG group. Inhibition of autophagy by bafilomycin A1 diminished the effect of glucose restoration on the phosphorylation of p70S6K. On the other hand, inhibition of ubiquitin-proteasome activity by MG132 did not affect the phosphorylation of p70S6K in response to glucose restoration. In conclusion, glucose starvation-induced autophagy partially account on the activation of translation initiation by glucose restoration.