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

Published online by Cambridge University Press:  09 December 2021

Qi Hao
Affiliation:
College of Animal Science, Yangtze University, Jingzhou434025, People’s Republic of China College of Life Science, Northeast Agricultural University, Harbin150030, People’s Republic of China
Lulu Wang
Affiliation:
College of Animal Science, Yangtze University, Jingzhou434025, People’s Republic of China College of Life Science, Northeast Agricultural University, Harbin150030, People’s Republic of China
Minghui Zhang
Affiliation:
College of Animal Science, Yangtze University, Jingzhou434025, People’s Republic of China
Zhe Wang
Affiliation:
College of Life Science, Northeast Agricultural University, Harbin150030, People’s Republic of China
Meng Li
Affiliation:
College of Life Science, Northeast Agricultural University, Harbin150030, People’s Republic of China
Xuejun Gao*
Affiliation:
College of Animal Science, Yangtze University, Jingzhou434025, People’s Republic of China College of Life Science, Northeast Agricultural University, Harbin150030, People’s Republic of China
*
*Corresponding author: Xuejun Gao, email gaoxj53901@163.com

Abstract

Taurine (Tau) has many profound physiological functions, but its role and molecular mechanism in muscle cells are still not fully understood. 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, mechanistic target of rapamycin protein (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 phosphoinositide 3-kinase (PI3K)-dependent manner. ARID4B knockdown (by small interfering RNA 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 signalling to mRNA expression and protein phosphorylation of mTOR, whereas ARID4B gene activation had stimulatory effects. Chromatin immunoprecipitation (ChIP)-PCR identified that all of ARID4B, H3K27ac and H3K27me3 bound to the −4368 to –4591 bp site in the mTOR promoter, and ChIP-quantitative PCR (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 of how Tau regulates anabolism in muscle cells.

Type
Full Papers
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Nutrition Society

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Footnotes

These authors contributed equally to this work.

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