Reduction of ribosome biogenesis with activation of the mTOR pathway in denervated atrophic muscle.

Mammalian target of rapamycin (mTOR) pathway positively regulates the cell growth through ribosome biogenesis in many cell type. In general, myostatin is understood to repress skeletal muscle hypertrophy through inhibition of mTOR pathway and myogenesis. However, these relationships have not been clarified in skeletal muscle undergoing atrophy. Here, we observed a significant decrease of skeletal muscle mass at 2 weeks after denervation. Unexpectedly, however, mTOR pathway and the expression of genes related to myogenesis were markedly increased, and that of myostatin was decreased. However, de novo ribosomal RNA synthesis and the levels of ribosomal RNAs were dramatically decreased in denervated muscle. These results indicate that ribosome biogenesis is strongly controlled by factors other than the mTOR pathway in denervated atrophic muscle. Finally, we assessed rRNA transcription factors expression and observed that TAFIa was the only factor decreased. TAFIa might be a one of the limiting factor for rRNA synthesis in denervated muscle.

Effect of Coenzyme Q10 supplementation on exercise-induced muscular injury of rats.

AIM: We aimed to examine the effect of Coenzyme Q10 (CoQ10) supplementation on the exhaustive exercise-induced injury and oxidative stress in skeletal muscle and liver. METHODS: Rats were divided into four groups: rest group [control (Con)-Rest; n = 6)], exercise group (Con-Ex; n = 6), rest group with CoQ10 supplement (CoQ10-Rest; n = 6), and exercise group with CoQ10 supplement (CoQ10-Ex; n = 6). The exercise groups were run on a treadmill until exhaustion. The CoQ10 supplemented groups received an oral administration of CoQ10 (300 mg kg(-1), 4 weeks). After 4 weeks, total CoQ concentration, creatine kinase (CK), glutamic-oxaloacetic transaminase (GOT), malondialdehyde (MDA), scavenging activity against reactive oxygen species [ROS; superoxide anions (O2*-) and hydroxyl radicals (HO*)] were measured. RESULTS: Total CoQ concentration in plasma, slow-twitch muscles (soleus and gastronemius deep portion), and liver were significantly increased by CoQ10 supplementation. Plasma CK was significantly higher in Con-Ex compared with Con-Rest, whereas there was no difference between CoQ10-Rest and CoQ10-Ex. There were no significant differences in muscle MDA in each group. Plasma GOT and liver MDA in exercise groups were significantly higher than that of rest groups, but not significantly different between CoQ10 supplemented groups and control groups. CoQ10 supplementation was not able to favorably influence ROS scavenging activity in skeletal muscle and liver. CONCLUSIONS: These data indicated that CoQ10 supplementation increased total CoQ concentration in the slow-twitch muscles, and was useful for reducing exhaustive exercise-induced muscular injury by enhancing stabilization of muscle cell membrane.