젖산이 골격근세포 내 마이오카인 발현에 미치는 영향
Effects of Lactic Acid on the Expression of Myokines in C2C12 Myotubes
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PURPOSE: During high intense exercise, the level of lactic acid (LA) increases over 10 mM, and LA has functions as an intermediate for muscular energy metabolism. However, the effects of LA on the level of myokines remain largely unknown. Aims of this study were to evaluate whether LA regulates the expression of myokines in C2C12 myotubes and to explore the regulatory mechanisms. METHODS: As a number of studies reported that intense exercise induced accumulation of 4-20 mM LA in blood, C2C12 myotubes were treated with LA of 0, 4 or 16 mM for 0.5, 1 or 4 hr. We measured mRNA and protein levels of myostatin (Mstn), and fibronectin type III domain-containing protein 5 (FNDC5) using real-time PCR or western blot, respectively. RESULTS: LA reduced the levels of both mRNA and protein of Mstn from 4 hr after treatment. The level of FNDC5 mRNA was increased by LA within 1 hr, which returned to the basal level at 4 hr. but not increased the expression of FNDC5 protein levels. The levels of phosphorylated 5-AMP activated protein kinase (p-AMPKThr172) show an increasing trend but its target phosphorylated acetyl-CoA carboxylase at Ser79 (p-ACCser79) was increased by LA within 30 min. CONCLUSIONS: Our results demonstrated the regulatory effect of LA on myokine expression, indicating that LA may be a metabolic factor contributing to secretory functions of skeletal muscle during high intensity physical exercise. In addition, LA accumulation at early time of physical exercise may influence on the signaling of intracellular energy metabolism, although further studies are needed to confirm our hypotheses.
Abstract
PURPOSE: During high intense exercise, the level of lactic acid (LA) increases over 10 mM, and LA has functions as an intermediate for muscular energy metabolism. However, the effects of LA on the level of myokines remain largely unknown. Aims of this study were to evaluate whether LA regulates the expression of myokines in C2C12 myotubes and to explore the regulatory mechanisms. METHODS: As a number of studies reported that intense exercise induced accumulation of 4-20 mM LA in blood, C2C12 myotubes were treated with LA of 0, 4 or 16 mM for 0.5, 1 or 4 hr. We measured mRNA and protein levels of myostatin (Mstn), and fibronectin type III domain-containing protein 5 (FNDC5) using real-time PCR or western blot, respectively. RESULTS: LA reduced the levels of both mRNA and protein of Mstn from 4 hr after treatment. The level of FNDC5 mRNA was increased by LA within 1 hr, which returned to the basal level at 4 hr. but not increased the expression of FNDC5 protein levels. The levels of phosphorylated 5-AMP activated protein kinase (p-AMPKThr172) show an increasing trend but its target phosphorylated acetyl-CoA carboxylase at Ser79 (p-ACCser79) was increased by LA within 30 min. CONCLUSIONS: Our results demonstrated the regulatory effect of LA on myokine expression, indicating that LA may be a metabolic factor contributing to secretory functions of skeletal muscle during high intensity physical exercise. In addition, LA accumulation at early time of physical exercise may influence on the signaling of intracellular energy metabolism, although further studies are needed to confirm our hypotheses.
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