2-D08 treatment regulates C2C12 myoblast proliferation and differentiation via the Erk1/2 and proteasome signaling pathways

• Published in: Journal of muscle research and cell motility 2021-06, Vol.42 (2), p.193-202
• Main Authors: Liu, Hyunju, Lee, Su-Mi, Joung, Hosouk
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animal Anatomy; Apoptosis; Biological Phenomena; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Differentiation; Cell growth; Cell Proliferation; Extracellular signal-regulated kinase; Gene expression; Histology; Kinases; Life Sciences; Long-term effects; Morphology; Motility; Musculoskeletal system; Myoblasts; Myoblasts - metabolism; MyoD Protein; Myogenesis; Myogenin; Myogenin - metabolism; Myosin; Myotubes; Original Paper; Post-translation; Proteasome Endopeptidase Complex; Proteasomes; Proteins; Proteomics; Signal Transduction; Skeletal muscle; SUMO protein; Ubiquitin
• ISSN: 0142-4319; 1573-2657
• DOI: 10.1007/s10974-021-09605-x

SUMOylation is one of the post-translational modifications that involves the covalent attachment of the small ubiquitin-like modifier (SUMO) to the substrate. SUMOylation regulates multiple biological processes, including myoblast proliferation, differentiation, and apoptosis. 2-D08 is a synthetically available flavone, which acts as a potent cell-permeable SUMOylation inhibitor. Its mechanism of action involves preventing the transfer of SUMO from the E2 thioester to the substrate without influencing SUMO-activating enzyme E1 (SAE-1/2) or E2 Ubc9-SUMO thioester formation. However, both the effects and mechanisms of 2-D08 on C2C12 myoblast cells remain unclear. In the present study, we found that treatment with 2-D08 inhibits C2C12 cell proliferation and differentiation. We confirmed that 2-D08 significantly hampers the viability of C2C12 cells. Additionally, it inhibited myogenic differentiation, decreasing myosin heavy chain (MHC), MyoD, and myogenin expression. Furthermore, we confirmed that 2-D08-mediated anti-myogenic effects impair myoblast differentiation and myotube formation, reducing the number of MHC-positive C2C12 cells. In addition, we found that 2-D08 induces the activation of ErK1/2 and the degradation of MyoD and myogenin in C2C12 cells. Taken together, these results indicated that 2-D08 treatment results in the deregulated proliferation and differentiation of myoblasts. However, further research is needed to investigate the long-term effects of 2-D08 on skeletal muscles.