Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway

In this study, we investigated the role and underlying molecular mechanism of Tau on protein synthesis and proliferation of C2C12 myoblast cells. Cells were treated with Tau (0, 60, 120, 180 and 240 μM) for 24 h. Tau dose-dependently promoted protein synthesis, cell proliferation, mTOR phosphorylation, and also AT-rich interaction domain 4B (ARID4B) expression, with the best stimulatory effects at 120 μM. LY 294002 treatment showed that Tau promoted ARID4B expression in a PI3K-dependent manner. ARID4B knockdown (by siRNA transfection for 24 h) prevented Tau from stimulating protein synthesis and cell proliferation, whereas ARID4B gene activation (using the CRISPR/dCas9 technology) had stimulatory effects. ARID4B knockdown abolished Tau signaling to mRNA expression and protein phosphorylation of mTOR, whereas ARID4B gene activation had stimulatory effects. ChIP-PCR identified that all of ARID4B, H3K27ac and H3K27me3 bound to the -4368∼-4591 bp site in the mTOR promoter, and ChIP-qPCR further detected that Tau stimulated ARID4B binding to this site. ARID4B knockdown or gene activation did not affect H3K27me3 binding to the mTOR promoter, but decreased or increased H3K27ac binding, respectively. Furthermore, ARID4B knockdown abolished the stimulation of Tau on H3K27ac binding to the mTOR promoter. In summary, these data uncover that Tau promotes protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway, providing a deep understanding ho...

Source: The British Journal of Nutrition - December 9, 2021 Category: Nutrition Authors: Qi Hao Lulu Wang Minghui Zhang Zhe Wang Meng Li Xuejun Gao Source Type: research