Clenbuterol Induces Cell Cycle Arrest in C2C12 Myoblasts by Delaying p27 Degradation through β-arrestin 2 Signaling

β₂-Adrenoceptor (β₂-AR) agonists promote muscle growth. The aim of this study was to elucidate some effects of the selective β₂-adrenoceptor agonist clenbuterol (CLB) on myoblast proliferation. We found that CLB induces cell cycle arrest in C2C12 myoblasts. This effect is partly due to the enhanced stability of p27, rather than the increased gene transcription via cAMP response element-binding protein (CREB). Specifically, CLB treatment enhanced the accumulation of p27 in the nucleus while depleting it from the cytosol via a mechanism that requires β₂-AR. Surprisingly, p27 accumulation was not reversed by the protein kinase A (PKA) inhibitor H-89, but interestingly, was alleviated by the knockdown of β-arrestin 2. Thus, our work provides a basis for β₂-AR agonists inhibit myoblasts proliferation through signaling via β₂-AR, β-arrestin 2, and p27.