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Glucose deprivation promotes activation of mTOR signaling pathway and protein synthesis in rat skeletal muscle cells

  • Muscle physiology
  • Published:
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Abstract

Signaling through mammalian target of rapamycin (mTOR) has been shown to play a central role in the regulation of skeletal muscle growth induced by a wide range of stimuli either mechanical or metabolic, such as growth factors and amino acids. Here, we demonstrate that mTOR and its downstream target, the ribosomal S6 kinase (p70S6K), are activated in L6 myocytes by a short-term glucose deprivation. Such response is specific of skeletal muscle and is likely responsible for the increased rate of protein synthesis and expression of the muscle-specific proteins during recovery from glucose deprivation. Nitric oxide and phosphatidylinositol-3-kinase (PI3K) are upstream positive regulators of mTOR since their pharmacological inhibition prevents the activation of p70S6K in response to glucose deprivation. We therefore propose a model of response to a brief period of glucose deprivation that may occur in skeletal muscle cells during resistance exercise and that may lead to protein accretion when blood flow recovers and all nutrients are again available.

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Abbreviations

4E-BP1:

Eukaryotic translation initiation factor 4E-binding protein 1

AICAR:

5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside

AMPK:

AMP-activated protein kinase

CC:

6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine (compound C)

JNK/MAPK:

c-Jun N-terminal kinase-mitogen-activated protein kinase

eIF4E:

Eukaryotic translation initiation factor 4E

L-NAME:

N(G)-nitro-l-arginine methyl ester

MAFbx:

Muscle atrophy F-box

mTOR:

Mammalian target of rapamycin

NO:

Nitric oxide

NOS:

Nitric oxide synthase

PI3K:

Phosphatidylinositol-3-kinase

p70S6K :

p70S6 kinase

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Acknowledgments

We wish to thank Drs Federica Tramontin and Cristina Gambardella for valuable assistance in some of the experiments and Prof. A. Calignano and G. Cirino for their continued interest. We thank Prof. L. Berrino and Dr B. Rinaldi for their kind donation of the MAFbx/atrogin-1 antibody. The authors wish to dedicate this manuscript to Prof. Alfredo Colonna who recently passed away.

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  1. Department of Pharmacy, University of Napoli “Federico II”, via D. Montesano 49, 80131, Naples, Italy

    Maria Concetta Miniaci, Maria Gabriella Dattolo, Carlo Irace, Antonella Capuozzo, Rita Santamaria & Pietro Scotto

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  1. Maria Concetta Miniaci
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  2. Maria Gabriella Dattolo
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  3. Carlo Irace
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Correspondence to Maria Concetta Miniaci or Pietro Scotto.

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Miniaci, M.C., Dattolo, M.G., Irace, C. et al. Glucose deprivation promotes activation of mTOR signaling pathway and protein synthesis in rat skeletal muscle cells. Pflugers Arch - Eur J Physiol 467, 1357–1366 (2015). https://doi.org/10.1007/s00424-014-1583-2

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