Cordycepin inhibits myogenesis via activating the ERK1/2 MAPK signalling pathway in C2C12 cells

by Selleckchem | Nov 05 2023

Cordycepin (with a molecular formula of C10H13N5O3), a natural adenosine isolated from Cordyceps militaris, has an important regulatory effect on skeletal muscle remodelling and quality maintenance. The aim of this study was to investigate the effect of cordycepin on myoblast differentiation and explore the underlying molecular mechanisms of this effect. Our results showed that cordycepin inhibited myogenesis by downregulating myogenic differentiation (MyoD) and myogenin (MyoG), preserved undifferentiated reserve cell pools by upregulating myogenic factor 5 (Myf5) and retinoblastoma-like protein p130 (p130), and enhanced energy reserves by decreasing intracellular reactive oxygen species (ROS) and enhancing mitochondrial membrane potential, mitochondrial mass, and ATP content. The effect of cordycepin on myogenesis was associated with increased phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2). PD98059 (a specific inhibitor of p-ERK1/2) attenuated the inhibitory effect of cordycepin on C2C12 differentiation. The present study reveals that cordycepin inhibits myogenesis through ERK1/2 MAPK signalling activation accompanied by an increase in skeletal muscle energy reserves and improving skeletal muscle oxidative stress, which may have implications for its further application for the prevention and treatment of degenerative muscle diseases caused by the depletion of depleted muscle stem cells.

Comments:

The study aimed to investigate the effects of cordycepin, a natural adenosine derived from Cordyceps militaris, on myoblast differentiation and explore the molecular mechanisms underlying this effect. The researchers found that cordycepin exerted several regulatory effects on skeletal muscle remodeling and quality maintenance.

One of the key findings was that cordycepin inhibited myogenesis, which is the process of muscle cell differentiation, by downregulating the expression of two important myogenic differentiation factors, namely, myogenic differentiation (MyoD) and myogenin (MyoG). By suppressing these factors, cordycepin prevented the differentiation of myoblasts into mature muscle cells.

Furthermore, cordycepin was found to preserve undifferentiated reserve cell pools by upregulating the expression of myogenic factor 5 (Myf5) and retinoblastoma-like protein p130 (p130). These factors are involved in maintaining a pool of undifferentiated muscle stem cells, ensuring a reservoir of cells available for future muscle repair and regeneration.

In addition to its effects on myoblast differentiation, cordycepin enhanced energy reserves within muscle cells. It achieved this by reducing intracellular reactive oxygen species (ROS) levels, improving mitochondrial function, including mitochondrial membrane potential and mitochondrial mass, and increasing ATP content. These changes indicate an improvement in cellular energy production and utilization.

The researchers also discovered a potential molecular mechanism underlying cordycepin's inhibitory effect on myogenesis. Cordycepin was found to increase the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), which is a member of the mitogen-activated protein kinase (MAPK) signaling pathway. To confirm the involvement of ERK1/2 activation, they used PD98059, a specific inhibitor of p-ERK1/2, which attenuated the inhibitory effect of cordycepin on myoblast differentiation in C2C12 cells.

Overall, the study suggests that cordycepin inhibits myogenesis through the activation of ERK1/2 MAPK signaling pathway. This inhibitory effect is accompanied by an increase in skeletal muscle energy reserves and improvements in skeletal muscle oxidative stress. These findings have potential implications for the prevention and treatment of degenerative muscle diseases caused by the depletion of muscle stem cells.