Patients with COVID-19 caused by the novel coronavirus (SARS-CoV-2) often present with long-term muscle weakness symptoms, which are closely related to metabolic disorders. Spike protein (SP) is the main structural protein of SARS-CoV-2, which can upregulate inflammatory factors and affect cell function. This study aims to explore the effect of spike protein on myogenic differentiation of C2C12 myoblasts and its mechanism of action through protein metabolism analysis. The spike protein significantly inhibits the proliferation and differentiation of C2C12 myoblasts, manifested as decreased cell density. Protein metabolism analysis revealed that after spike protein intervention, the pathways related to protein synthesis within cells were inhibited, while those related to protein degradation were activated, indicating that protein metabolism disorders might be an important mechanism of cell damage. FAK transfection can significantly improve cell damage caused by spike proteins, promote myogenic differentiation, and partially restore the normal expression of protein metabolic pathways.
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