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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

Myosin heavy chain 2A and α-Actin expression in human and murine skeletal muscles at feeding; particularly amino acids

Authors: Britt-Marie Iresjö, Kent Lundholm

Published in: Journal of Translational Medicine | Issue 1/2012

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Abstract

Background

Protein dynamics during non-steady state conditions as feeding are complex. Such studies usually demand combinations of methods to give conclusive information, particularly on myofibrillar proteins with slow turnover. Therefore, time course transcript analyses were evaluated as possible means to monitor changes in myofibrillar biosynthesis in skeletal muscles in conditions with clinical nutrition; i.e. long term exposure of nutrients.

Methods

Muscle tissue from overnight intravenously fed surgical patients were used as a model combined with muscle tissue from starved and refed mice as well as cultured L6 muscle cells. Transcripts of acta 1 (α-actin), mhc2A (myosin) and slc38 a2/Snat 2 (amino acid transporter) were quantified (qPCR) as markers of muscle protein dynamics.

Results

Myosin heavy chain 2A transcripts decreased significantly in skeletal muscle tissue from overnight parenterally fed patients but did not change significantly in orally refed mice. Alpha-actin transcripts did not change significantly in muscle cells from fed patients, mice or cultured L6 cells during provision of AA. The AA transporter Snat 2 decreased in L6 cells refed by all AA and by various combinations of AA but did not change during feeding in muscle tissue from patients or mice.

Conclusion

Our results confirm that muscle cells are sensitive to alterations in extracellular concentrations of AA for induction of protein synthesis and anabolism. However, transcripts of myofibrillar proteins and amino acid transporters showed complex alterations in response to feeding with provision of amino acids. Therefore, muscle tissue transcript levels of actin and myosin do not reflect protein accretion in skeletal muscles at feeding.
Appendix
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Literature
1.
Waterlow JC, Garlick P, Millward DJ: Protein turnover in mammalian tissues and in the whole body. 1978, Amsterdam: Elsevier/North-Holland Biomedical Press
2.
Garlick PJ, Clugston GA, McNurlan MA, Preedy VR, Fern EB: Nutrition and protein turnover. Biochem Soc Trans. 1982, 10: 290-291.CrossRefPubMed
3.
Garlick PJ, McNurlan MA, Ballmer PE: Influence of dietary protein intake on whole-body protein turnover in humans. Diabetes Care. 1991, 14: 1189-1198. 10.2337/diacare.14.12.1189.CrossRefPubMed
4.
McNurlan MA, Garlick PJ: Influence of nutrient intake on protein turnover. Diabetes Metab Rev. 1989, 5: 165-189. 10.1002/dmr.5610050206.CrossRefPubMed
5.
Millward DJ, Nnanyelugo DO, James WP, Garlick PJ: Protein metabolism in skeletal muscle: the effect of feeding and fasting on muscle RNA, free amino acids and plasma insulin concentrations. Br J Nutr. 1974, 32: 127-142. 10.1079/BJN19740063.CrossRefPubMed
6.
Avruch J, Long X, Ortiz-Vega S, Rapley J, Papageorgiou A, Dai N: Amino acid regulation of TOR complex 1. Am J Physiol Endocrinol Metab. 2009, 296: E592-E602. 10.1152/ajpendo.90645.2008.CrossRefPubMedPubMedCentral
7.
James WP, Garlick PJ, Sender PM, Waterlow JC: Studies of amino acid and protein metabolism in normal man with L-[U- 14C]tyrosine. Clin Sci Mol Med. 1976, 50: 525-532.PubMed
8.
Ballmer PE, McNurlan MA, Milne E, Heys SD, Buchan V, Calder AG, Garlick PJ: Measurement of albumin synthesis in humans: a new approach employing stable isotopes. Am J Physiol. 1990, 259: E797-E803.PubMed
9.
Calder AG, Anderson SE, Grant I, McNurlan MA, Garlick PJ: The determination of low d5-phenylalanine enrichment (0.002-0.09 atom percent excess), after conversion to phenylethylamine, in relation to protein turnover studies by gas chromatography/electron ionization mass spectrometry. Rapid Commun Mass Spectrom. 1992, 6: 421-424. 10.1002/rcm.1290060704.CrossRefPubMed
10.
Wagenmakers AJ: Tracers to investigate protein and amino acid metabolism in human subjects. Proc Nutr Soc. 1999, 58: 987-1000. 10.1017/S0029665199001305.CrossRefPubMed
11.
Fern EB, Garlick PJ: The specific radioactivity of the tissue free amino acid pool as a basis for measuring the rate of protein synthesis in the rat in vivo. Biochem J. 1974, 142: 413-419.CrossRefPubMedPubMedCentral
12.
Iresjo BM, Svanberg E, Lundholm K: Reevaluation of amino acid stimulation of protein synthesis in murine- and human-derived skeletal muscle cells assessed by independent techniques. Am J Physiol Endocrinol Metab. 2005, 288: E1028-E1037.CrossRefPubMed
13.
El-Haroun ER, Bureau DP, Cant JP: A mechanistic model of nutritional control of protein synthesis in animal tissues. J Theor Biol. 2010, 262: 361-369. 10.1016/j.jtbi.2009.09.034.CrossRefPubMed
14.
Wolfe RR, Song J, Sun J, Zhang XJ: Total aminoacyl-transfer RNA pool is greater in liver than muscle in rabbits. J Nutr. 2007, 137: 2333-2338.PubMed
15.
Iresjo BM, Körner U, Hyltander A, Ljungman D, Lundholm K: Initiation factor for translation of proteins in the rectus abdominis muscle from patients on overnight standard parenteral nutrition before surgery. Clin Sci. 2008, 114: 603-610. 10.1042/CS20070359.CrossRefPubMed
16.
Lundholm K, Bennegard K, Zachrisson H, Lundgren F, Eden E, Moller-Loswick AC: Transport kinetics of amino acids across the resting human leg. J Clin Invest. 1987, 80: 763-771. 10.1172/JCI113132.CrossRefPubMedPubMedCentral
17.
Lundholm K, Schersten T: Protein synthesis in human skeletal muscle tissue: influence of insulin and amino acids. Eur J Clin Invest. 1977, 7: 531-536. 10.1111/j.1365-2362.1977.tb01647.x.CrossRefPubMed
18.
Svanberg E, Jefferson LS, Lundholm K, Kimball SR: Postprandial stimulation of muscle protein synthesis is independent of changes in insulin. Am J Physiol. 1997, 272: E841-E847.PubMed
19.
Svanberg E, Zachrisson H, Ohlsson C, Iresjo BM, Lundholm KG: Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding. Am J Physiol. 1996, 270: E614-E620.PubMed
20.
Svanberg E, Moller-Loswick AC, Matthews DE, Korner U, Andersson M, Lundholm K: Effects of amino acids on synthesis and degradation of skeletal muscle proteins in humans. Am J Physiol. 1996, 271: E718-E724.PubMed
21.
Arnal M, Obled C, Attaix D, Patureau-Mirand P, Bonin D: Dietary control of protein turnover. Diabete Metab. 1987, 13: 630-642.PubMed
22.
Davis TA, Reeds PJ: Of flux and flooding: the advantages and problems of different isotopic methods for quantifying protein turnover in vivo: II, Methods based on the incorporation of a tracer. Curr Opin Clin Nutr Metab Care. 2001, 4: 51-56. 10.1097/00075197-200101000-00010.CrossRefPubMed
23.
Li JB, Fulks RM, Goldberg AL: Evidence that the intracellular pool of tyrosine serves as precursor for protein synthesis in muscle. J Biol Chem. 1973, 248: 7272-7275.PubMed
24.
Garlick PJ: An analysis of errors in estimation of the rate of protein synthesis by constant infusion of a labelled amino acid. Biochem J. 1978, 176: 402-405.CrossRefPubMedPubMedCentral
25.
Svanberg E, Ennion S, Isgaard J, Goldspink G: Postprandial resynthesis of myofibrillar proteins is translationally rather than transcriptionally regulated in human skeletal muscle. Nutrition. 2000, 16: 42-46. 10.1016/S0899-9007(99)00226-9.CrossRefPubMed
26.
Hyltander A, Warnold I, Eden E, Lundholm K: Effect on whole-body protein synthesis after institution of intravenous nutrition in cancer and non-cancer patients who lose weight. Eur J Cancer. 1991, 27: 16-21. 10.1016/0277-5379(91)90051-E.CrossRefPubMed
27.
Moller-Loswick AC, Bennegard K, Lundholm K: The forearm and leg perfusion techniques in man do not give the same metabolic information. Clin Physiol. 1991, 11: 385-395. 10.1111/j.1475-097X.1991.tb00667.x.CrossRefPubMed
28.
Bennegard K, Eden E, Ekman L, Schersten T, Lundholm K: Metabolic response of whole body and peripheral tissues to enteral nutrition in weight-losing cancer and noncancer patients. Gastroenterology. 1983, 85: 92-99.PubMed
29.
Essen P, McNurlan MA, Wernerman J, Milne E, Vinnars E, Garlick PJ: Short-term starvation decreases skeletal muscle protein synthesis rate in man. Clin Physiol. 1992, 12: 287-299. 10.1111/j.1475-097X.1992.tb00834.x.CrossRefPubMed
30.
Baillie AG, Garlick PJ: Responses of protein synthesis in different skeletal muscles to fasting and insulin in rats. Am J Physiol. 1991, 260: E891-E896.PubMed
31.
Millward DJ, Garlick PJ, Nnanyelugo DO, Waterlow JC: The relative importance of muscle protein synthesis and breakdown in the regulation of muscle mass. Biochem J. 1976, 156: 185-188.CrossRefPubMedPubMedCentral
32.
Tjader I, Essen P, Thorne A, Garlick PJ, Wernerman J, McNurlan MA: Muscle protein synthesis rate decreases 24 hours after abdominal surgery irrespective of total parenteral nutrition. JPEN J Parenter Enteral Nutr. 1996, 20: 135-138. 10.1177/0148607196020002135.CrossRefPubMed
33.
Tawa NE, Goldberg AL: Suppression of muscle protein turnover and amino acid degradation by dietary protein deficiency. Am J Physiol. 1992, 263: E317-E325.PubMed
34.
Balagopal P, Ljungqvist O, Nair KS: Skeletal muscle myosin heavy-chain synthesis rate in healthy humans. Am J Physiol. 1997, 272: E45-E50.PubMed
35.
Hasten DL, Morris GS, Ramanadham S, Yarasheski KE: Isolation of human skeletal muscle myosin heavy chain and actin for measurement of fractional synthesis rates. Am J Physiol. 1998, 275: E1092-E1099.PubMedPubMedCentral
36.
Bates PC, Grimble GK, Sparrow MP, Millward DJ: Myofibrillar protein turnover. Synthesis of protein-bound 3-methylhistidine, actin, myosin heavy chain and aldolase in rat skeletal muscle in the fed and starved states. Biochem J. 1983, 214: 593-605.CrossRefPubMedPubMedCentral
37.
Bates PC, Millward DJ: Myofibrillar protein turnover, Synthesis rates of myofibrillar and sarcoplasmic protein fractions in different muscles and the changes observed during postnatal development and in response to feeding and starvation. Biochem J. 1983, 214: 587-592.CrossRefPubMedPubMedCentral
38.
Harridge SD: Plasticity of human skeletal muscle: gene expression to in vivo function. Exp Physiol. 2007, 92: 783-797. 10.1113/expphysiol.2006.036525.CrossRefPubMed
39.
Weiss A, Leinwand LA: The mammalian myosin heavy chain gene family. Annu Rev Cell Dev Biol. 1996, 12: 417-439. 10.1146/annurev.cellbio.12.1.417.CrossRefPubMed
40.
Gunawan AM, Park SK, Pleitner JM, Feliciano L, Grant AL, Gerrard DE: Contractile protein content reflects myosin heavy-chain isoform gene expression. J Anim Sci. 2007, 85: 1247-1256. 10.2527/jas.2006-511.CrossRefPubMed
41.
Toth MJ, Tchernof A: Effect of age on skeletal muscle myofibrillar mRNA abundance: relationship to myosin heavy chain protein synthesis rate. Exp Gerontol. 2006, 41: 1195-1200. 10.1016/j.exger.2006.08.005.CrossRefPubMed
42.
Glass DJ: Molecular mechanisms modulating muscle mass. Trends Mol Med. 2003, 9: 344-350. 10.1016/S1471-4914(03)00138-2.CrossRefPubMed
43.
Glass DJ: Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol. 2005, 37: 1974-1984. 10.1016/j.biocel.2005.04.018.CrossRefPubMed
44.
Sundaram P, Pang Z, Miao M, Yu L, Wing SS: USP19-deubiquitinating enzyme regulates levels of major myofibrillar proteins in L6 muscle cells. Am J Physiol Endocrinol Metab. 2009, 297: E1283-E1290. 10.1152/ajpendo.00409.2009.CrossRefPubMed
45.
Giger JM, Bodell PW, Zeng M, Baldwin KM, Haddad F: Rapid muscle atrophy response to unloading: pretranslational processes involving MHC and actin. J Appl Physiol. 2009, 107: 1204-1212. 10.1152/japplphysiol.00344.2009.CrossRefPubMedPubMedCentral
46.
Haddad F, Roy RR, Zhong H, Edgerton VR, Baldwin KM: Atrophy responses to muscle inactivity. I. Cellular markers of protein deficits. J Appl Physiol. 2003, 95: 781-790.CrossRefPubMed
47.
Svanberg E, Kiri A, Isgaard J, Goldspink G: Semi-starvation alters myofibrillar mRNA concentrations to expedite rapid recovery of muscle protein stores following feeding. Eur J Clin Invest. 2000, 30: 722-728. 10.1046/j.1365-2362.2000.00701.x.CrossRefPubMed
48.
Atherton PJ, Etheridge T, Watt PW, Wilkinson D, Selby A, Rankin D, Smith K, Rennie MJ: Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. Am J Clin Nutr. 2010, 92: 1080-1088. 10.3945/ajcn.2010.29819.CrossRefPubMed
49.
Hundal HS, Taylor PM: Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab. 2009, 296: E603-E613. 10.1152/ajpendo.91002.2008.CrossRefPubMedPubMedCentral
50.
Drummond MJ, Glynn EL, Fry CS, Timmerman KL, Volpi E, Rasmussen BB: An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle. Am J Physiol Endocrinol Metab. 2010, 298: E1011-E1018. 10.1152/ajpendo.00690.2009.CrossRefPubMedPubMedCentral
51.
Waterlow JC, Garlick P, Millward DI: Free amino acids. Protein turnover in mammalian tissues and in the whole body. 1978, Amsterdam: Elsevier/North-Holland Biomedical Press, 117-176.
52.
Hyde R, Taylor PM, Hundal HS: Amino acid transporters: roles in amino acid sensing and signalling in animal cells. Biochem J. 2003, 373: 1-18. 10.1042/BJ20030405.CrossRefPubMedPubMedCentral
53.
Kashiwagi H, Yamazaki K, Takekuma Y, Ganapathy V, Sugawara M: Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation. Amino Acids. 2009, 36: 219-230. 10.1007/s00726-008-0050-9.CrossRefPubMed
54.
Evans K, Nasim Z, Brown J, Butler H, Kauser S, Varoqui H, Erickson JD, Herbert TP, Bevington A: Acidosis-sensing glutamine pump SNAT2 determines amino acid levels and mammalian target of rapamycin signalling to protein synthesis in L6 muscle cells. J Am Soc Nephrol. 2007, 18: 1426-1436. 10.1681/ASN.2006091014.CrossRefPubMed
55.
Aizawa K, Iemitsu M, Maeda S, Jesmin S, Otsuki T, Mowa CN, Miyauchi T, Mesaki N: Expression of steroidogenic enzymes and synthesis of sex steroid hormones from DHEA in skeletal muscle of rats. Am J Physiol Endocrinol Metab. 2007, 292: E577-E584.CrossRefPubMed
56.
Payne AH, Hales DB: Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev. 2004, 25: 947-970. 10.1210/er.2003-0030.CrossRefPubMed
57.
Hu J, Zhang Z, Shen WJ, Azhar S: Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones. Nutr Metab (Lond). 2010, 7: 47-10.1186/1743-7075-7-47.CrossRef
58.
Aizawa K, Iemitsu M, Otsuki T, Maeda S, Miyauchi T, Mesaki N: Sex differences in steroidogenesis in skeletal muscle following a single bout of exercise in rats. J Appl Physiol. 2008, 104: 67-74. 10.1007/s00421-008-0780-0.CrossRefPubMed
59.
Garlick PJ, Preedy VR, Reeds PJ: Regulation of protein turnover in vivo by insulin and amino acids. Prog Clin Biol Res. 1985, 180: 555-564.PubMed
60.
61.
Lundholm K, Edstrom S, Ekman L, Karlberg I, Walker P, Schersten T: Protein degradation in human skeletal muscle tissue: the effect of insulin, leucine, amino acids and ions. Clin Sci. 1981, 60: 319-326.CrossRefPubMed
62.
Garlick PJ, Grant I: Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin, Effect of branched-chain amino acids. Biochem J. 1988, 254: 579-584.CrossRefPubMedPubMedCentral
63.
Adibi SA: Metabolism of branched-chain amino acids in altered nutrition. Metabolism. 1976, 25: 1287-1302. 10.1016/S0026-0495(76)80012-1.CrossRefPubMed
64.
Holecek M: Relation between glutamine, branched-chain amino acids, and protein metabolism. Nutrition. 2002, 18: 130-133. 10.1016/S0899-9007(01)00767-5.CrossRefPubMed
65.
66.
Fulks RM, Li JB, Goldberg AL: Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm. J Biol Chem. 1975, 250: 290-298.PubMed
67.
May ME, Buse MG: Effects of branched-chain amino acids on protein turnover. Diabetes Metab Rev. 1989, 5: 227-245. 10.1002/dmr.5610050303.CrossRefPubMed
68.
69.
Metadata
Title
Myosin heavy chain 2A and α-Actin expression in human and murine skeletal muscles at feeding; particularly amino acids
Authors
Britt-Marie Iresjö
Kent Lundholm
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-238

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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