Trans-omic Analysis Reveals ROS-Dependent Pentose Phosphate Pathway Activation after High-Frequency Electrical Stimulation in C2C12 Myotubes

• Main Authors: Daisuke Hoshino, Kentaro Kawata, Katsuyuki Kunida, Atsushi Hatano, Katsuyuki Yugi, Takumi Wada, Masashi Fujii, Takanori Sano, Yuki Ito, Yasuro Furuichi, Yasuko Manabe, Yutaka Suzuki, Nobuharu L. Fujii, Tomoyoshi Soga, Shinya Kuroda
• Format: Article
• Language: English
• Published: Elsevier 2020-10-01
• Series: iScience
• Subjects: Biochemistry; Physiology; Human Metabolism; Omics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004220307501

Summary: Skeletal muscle adaptation is mediated by cooperative regulation of metabolism, signal transduction, and gene expression. However, the global regulatory mechanism remains unclear. To address this issue, we performed electrical pulse stimulation (EPS) in differentiated C2C12 myotubes at low and high frequency, carried out metabolome and transcriptome analyses, and investigated phosphorylation status of signaling molecules. EPS triggered extensive and specific changes in metabolites, signaling phosphorylation, and gene expression during and after EPS in a frequency-dependent manner. We constructed trans-omic network by integrating these data and found selective activation of the pentose phosphate pathway including metabolites, upstream signaling molecules, and gene expression of metabolic enzymes after high-frequency EPS. We experimentally validated that activation of these molecules after high-frequency EPS was dependent on reactive oxygen species (ROS). Thus, the trans-omic analysis revealed ROS-dependent activation in signal transduction, metabolome, and transcriptome after high-frequency EPS in C2C12 myotubes, shedding light on possible mechanisms of muscle adaptation.