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Modulation of muscle protein synthesis by amino acids: what consequences for the secretome? A preliminary in vitro study

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Abstract

The modulation by amino acids of muscle secretome is largely unknown. In this study, we investigate the effect of hyperaminoacidemia or specific amino acids (citrulline or leucine) on protein synthesis and secretome in myotubes. All conditions stimulate muscle protein synthesis, and secretome is differently modulated depending of the amino acids considered. In conclusion, the activation of protein synthesis by amino acids induces different modulations of the muscle secretome, proposing a new role of amino acids in the regulation of muscle function.

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Abbreviations

AA:

Amino acid

CIT:

Citrulline

LEU:

Leucine

MPS:

Muscle protein synthesis

References

  • Baumgardt SL, Paterson M, Leucker TM, Fang J, Zhang DX, Bosnjak ZJ, Warltier DC, Kersten JR, Ge Z-D (2016) Chronic co-administration of sepiapterin and l-citrulline ameliorates diabetic cardiomyopathy and myocardial ischemia/reperfusion injury in obese type 2 diabetic mice. Circ Heart Fail 9:e002424

    Article  CAS  Google Scholar 

  • Bengoa JM, Sitrin MD, Wood RJ, Rosenberg IH (1983) Amino acid-induced hypercalciuria in patients on total parenteral nutrition. Am J Clin Nutr 38:264–269

    Article  CAS  Google Scholar 

  • Breitwieser FP, Colinge J (2013) Isobar(PTM): a software tool for the quantitative analysis of post-translationally modified proteins. J Proteom 90:77–84

    Article  CAS  Google Scholar 

  • Breitwieser FP, Müller A, Dayon L, Köcher T, Hainard A, Pichler P, Schmidt-Erfurth U, Superti-Furga G, Sanchez J-C, Mechtler K, Bennett KL, Colinge J (2011) General statistical modeling of data from protein relative expression isobaric tags. J Proteome Res 10:2758–2766

    Article  CAS  Google Scholar 

  • Chenau J, Michelland S, de Fraipont F, Josserand V, Coll J-L, Favrot M-C, Seve M (2009) The cell line secretome, a suitable tool for investigating proteins released in vivo by tumors: application to the study of p53-modulated proteins secreted in lung cancer cells. J Proteome Res 8:4579–4591

    Article  CAS  Google Scholar 

  • Clarke ER, Martell AE (1970) Metal chelates of arginine and related ligands. J Inorg Nucl Chem 32:911–926

    Article  CAS  Google Scholar 

  • Figueroa A, Sanchez-Gonzalez MA, Wong A, Arjmandi BH (2012) Watermelon extract supplementation reduces ankle blood pressure and carotid augmentation index in obese adults with prehypertension or hypertension. Am J Hypertens 25:640–643

    Article  CAS  Google Scholar 

  • Figueroa A, Wong A, Jaime SJ, Gonzales JU (2017) Influence of l-citrulline and watermelon supplementation on vascular function and exercise performance. Curr Opin Clin Nutr Metab Care 20:92–98

    Article  CAS  Google Scholar 

  • Fujita S, Dreyer HC, Drummond MJ, Glynn EL, Cadenas JG, Yoshizawa F, Volpi E, Rasmussen BB (2007) Nutrient signalling in the regulation of human muscle protein synthesis. J Physiol 582:813–823

    Article  CAS  Google Scholar 

  • Gorissen SHM, Rémond D, van Loon LJC (2015) The muscle protein synthetic response to food ingestion. Meat Sci 109:96–100

    Article  CAS  Google Scholar 

  • Goron A, Lamarche F, Blanchet S, Delangle P, Schlattner U, Fontaine E, Moinard C (2019) Citrulline stimulates muscle protein synthesis, by reallocating ATP consumption to muscle protein synthesis. J Cachexia Sarcopenia Muscle. https://doi.org/10.1002/jcsm.12435

    Article  PubMed  PubMed Central  Google Scholar 

  • Ham DJ, Lynch GS, Koopman R (2016) Amino acid sensing and activation of mechanistic target of rapamycin complex 1: implications for skeletal muscle. Curr Opin Clin Nutr Metab Care 19:67–73

    Article  CAS  Google Scholar 

  • Jackson AA (2000) Nutrients, growth, and the development of programmed metabolic function. Adv Exp Med Biol 478:41–55

    Article  CAS  Google Scholar 

  • Le Plénier S, Walrand S, Noirt R, Cynober L, Moinard C (2012) Effects of leucine and citrulline versus non-essential amino acids on muscle protein synthesis in fasted rat: a common activation pathway? Amino Acids 43:1171–1178

    Article  Google Scholar 

  • Le Plénier S, Goron A, Sotiropoulos A, Archambault E, Guihenneuc C, Walrand S, Salles J, Jourdan M, Neveux N, Cynober L, Moinard C (2017) Citrulline directly modulates muscle protein synthesis via the PI3K/MAPK/4E-BP1 pathway in a malnourished state: evidence from in vivo, ex vivo, and in vitro studies. Am J Physiol Endocrinol Metab 312:E27–E36

    Article  Google Scholar 

  • Lehmann SG, Bourgoin-Voillard S, Seve M, Rachidi W (2017) Tubulin beta-3 chain as a new candidate protein biomarker of human skin aging: a preliminary study. Oxid Med Cell Longev 2017:5140360

    Article  Google Scholar 

  • Lin G, Wang X, Wu G, Feng C, Zhou H, Li D, Wang J (2014) Improving amino acid nutrition to prevent intrauterine growth restriction in mammals. Amino Acids 46:1605–1623

    Article  CAS  Google Scholar 

  • Luo J, Wang L-P, Hu H-F, Zhang L, Li Y-L, Ai L-M, Mu H-Y, Kun-Wang (2015) Cystatin C and cardiovascular or all-cause mortality risk in the general population: a meta-analysis. Clin Chim Acta Int J Clin Chem 450:39–45

    Article  CAS  Google Scholar 

  • Maurer M, Müller AC, Parapatics K, Pickl WF, Wagner C, Rudashevskaya EL, Breitwieser FP, Colinge J, Garg K, Griss J, Bennett KL, Wagner SN (2014) Comprehensive comparative and semiquantitative proteome of a very low number of native and matched epstein-barr-virus-transformed B lymphocytes infiltrating human melanoma. J Proteome Res 13:2830–2845

    Article  CAS  Google Scholar 

  • Ohanna M, Sobering AK, Lapointe T, Lorenzo L, Praud C, Petroulakis E, Sonenberg N, Kelly PA, Sotiropoulos A, Pende M (2005) Atrophy of S6K1(–/–) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control. Nat Cell Biol 7:286–294

    Article  CAS  Google Scholar 

  • Osowska S, Duchemann T, Walrand S, Paillard A, Boirie Y, Cynober L, Moinard C (2006) Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab 291:E582–E586

    Article  CAS  Google Scholar 

  • Pascovici D, Song X, Solomon PS, Winterberg B, Mirzaei M, Goodchild A, Stanley WC, Liu J, Molloy MP (2015) Combining protein ratio p-values as a pragmatic approach to the analysis of multirun iTRAQ experiments. J Proteome Res 14:738–746

    Article  CAS  Google Scholar 

  • Pedersen BK (2013) Muscle as a secretory organ. Compr Physiol 3:1337–1362

    PubMed  Google Scholar 

  • Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8:457–465

    Article  CAS  Google Scholar 

  • Pencharz PB, Ball RO (2004) Amino acid needs for early growth and development. J Nutr 134:1566S–1568S

    Article  CAS  Google Scholar 

  • Prod’homme M, Rieu I, Balage M, Dardevet D, Grizard J (2004) Insulin and amino acids both strongly participate to the regulation of protein metabolism. Curr Opin Clin Nutr Metab Care 7:71–77

    Article  Google Scholar 

  • Prod’homme M, Balage M, Debras E, Farges M-C, Kimball S, Jefferson L, Grizard J (2005) Differential effects of insulin and dietary amino acids on muscle protein synthesis in adult and old rats. J Physiol 563:235–248

    Article  Google Scholar 

  • Romero MJ, Platt DH, Caldwell RB, Caldwell RW (2006) Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev 24:275–290

    Article  CAS  Google Scholar 

  • Ropo M, Blum V, Baldauf C (2016) Trends for isolated amino acids and dipeptides: conformation, divalent ion binding, and remarkable similarity of binding to calcium and lead. Sci Rep 6:35772

    Article  CAS  Google Scholar 

  • Sanchez-Gonzalez MA, Koutnik AP, Ramirez K, Wong A, Figueroa A (2013) The effects of short term l-citrulline supplementation on wave reflection responses to cold exposure with concurrent isometric exercise. Am J Hypertens 26:518–526

    Article  CAS  Google Scholar 

  • Sialana FJ, Gulyassy P, Májek P, Sjöstedt E, Kis V, Müller AC, Rudashevskaya EL, Mulder J, Bennett KL, Lubec G (2016) Mass spectrometric analysis of synaptosomal membrane preparations for the determination of brain receptors, transporters and channels. Proteomics 16:2911–2920

    Article  CAS  Google Scholar 

  • Stipanuk MH (2007) Leucine and protein synthesis: mTOR and beyond. Nutr Rev 65:122–129

    Article  Google Scholar 

  • Wu G (2016) Dietary protein intake and human health. Food Funct 7:1251–1265

    Article  CAS  Google Scholar 

  • Wu G, Collins JK, Perkins-Veazie P, Siddiq M, Dolan KD, Kelly KA, Heaps CL, Meininger CJ (2007) Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J Nutr 137:2680–2685

    Article  CAS  Google Scholar 

  • Wu G, Bazer FW, Dai Z, Li D, Wang J, Wu Z (2014) Amino acid nutrition in animals: protein synthesis and beyond. Annu Rev Anim Biosci 2:387–417

    Article  CAS  Google Scholar 

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Funding

A. Goron was supported by a grant from Agir pour les maladies chroniques. C. Breuillard and this work were supported by the UGA Foundation (“Chaire Nutrition des Séniors”) thanks to the sponsorship of Findus.

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Authors and Affiliations

Authors

Contributions

AG, CB contributed to all parts of this work. VC contributed to the experimental proteomics part of this work. SB-V and MS contributed to the analytic proteomics part of this work. CM contributed to the lead of this work and the redaction of the article.

Corresponding author

Correspondence to Christophe Moinard.

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Conflict of interest

C. Moinard and C. Breuillard are shareholders in the Citrage company. Other authors have no conflicts of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Handling Editor: F. Blachier.

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Goron, A., Breuillard, C., Cunin, V. et al. Modulation of muscle protein synthesis by amino acids: what consequences for the secretome? A preliminary in vitro study. Amino Acids 51, 1681–1688 (2019). https://doi.org/10.1007/s00726-019-02796-1

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  • DOI: https://doi.org/10.1007/s00726-019-02796-1

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