caa a22 4500 606236066 CHVBK 20210128101245.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s11010-015-2446-7 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2446-7 Mechanical stretch activates mammalian target of rapamycin and AMP-activated protein kinase pathways in skeletal muscle cells [Elektronische Daten] [Naoya Nakai, Fuminori Kawano, Ken Nakata] Cellular protein synthesis is believed to be antagonistically regulated by mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways. In the present study, we examined the relationship between mTOR/p70 S6 kinase (p70S6K) and AMPK in response to mechanical stretch. C2C12 myoblasts were grown on a silicone elastomer chamber to confluence and further cultured in differentiation medium for 4days to form multinucleated myotubes. Cells were subjected to 15% cyclic uniaxial stretch for 4h at a frequency of 1Hz. Phosphorylation of p70S6K at threonine 389 and AMPK at threonine 172 of the catalytic α subunit were concomitantly increased by mechanical stretch. Stimulation of the mTOR pathway by adding leucine and insulin increased the phosphorylation of p70S6K without inactivation of AMPK. In contrast, addition of compound C, a pharmacological inhibitor of AMPK, increased the phosphorylation of p70S6K in stretched cells. Activation of AMPK by the addition of 5-amino-4-imidazolecarboxamide ribonucleoside reduced the phosphorylation of p70S6K in response to mechanical stretch. In conclusion, crosstalk between mTOR and AMPK signaling was not tightly regulated in response to physiological stimuli, such as mechanical stress and/or nutrients. However, pharmacological modulation of AMPK influenced the mTOR/p70S6K signaling pathway. Springer Science+Business Media New York, 2015 Mechanical stimulus nationallicence Mammalian target of rapamycin nationallicence AMP-activated protein kinase nationallicence Protein synthesis nationallicence Nakai Naoya Department of Health and Sports Sciences, Graduate School of Medicine, Osaka University, 1-17 Machikaneyama-cho, 560-0043, Toyonaka, Osaka, Japan aut Kawano Fuminori Department of Health and Sports Sciences, Graduate School of Medicine, Osaka University, 1-17 Machikaneyama-cho, 560-0043, Toyonaka, Osaka, Japan aut Nakata Ken Department of Health and Sports Sciences, Graduate School of Medicine, Osaka University, 1-17 Machikaneyama-cho, 560-0043, Toyonaka, Osaka, Japan aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 285-292 0300-8177 406:1-2<285 2015 406 11010 https://doi.org/10.1007/s11010-015-2446-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2446-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nakai Naoya Department of Health and Sports Sciences, Graduate School of Medicine, Osaka University, 1-17 Machikaneyama-cho, 560-0043, Toyonaka, Osaka, Japan aut NATIONALLICENCE 700 1- Kawano Fuminori Department of Health and Sports Sciences, Graduate School of Medicine, Osaka University, 1-17 Machikaneyama-cho, 560-0043, Toyonaka, Osaka, Japan aut NATIONALLICENCE 700 1- Nakata Ken Department of Health and Sports Sciences, Graduate School of Medicine, Osaka University, 1-17 Machikaneyama-cho, 560-0043, Toyonaka, Osaka, Japan aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 285-292 0300-8177 406:1-2<285 2015 406 11010