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The regulatory effects of coded amino acids on basic cellular processes in young and old animals

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Abstract

Aspects of the regulatory effects of coded amino acids on basic cellular processes, viz., proliferation and apoptosis, are discussed. These effects occur due to the regulation of specific genes by amino acids at the transcriptional and translational levels, which leads to the initiation of regulatory cascades of many of the main cellular processes. Investigations in organotypic cultures of tissues of different geneses have demonstrated that different amino acids stimulate cellular proliferation or apoptosis. The group of low-molecular weight hydrophilic amino acids with charged chains influences cell proliferation in tissues of mesodermal genesis. Another group of high-molecular weight hydrophobic amino acids acts on tissues of ectodermal genesis. Thus, the coded amino acids are not only the structural elements of proteins, but can also actively participate in the regulation of specific genes that control the cellular cycle. The number of active amino acids is decreased by 2.7 times in explants from old animals as compared to young ones, reflecting the disturbance in amino-acid transport and gene expression by aging.

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References

  1. Belokrylov, G.A., Derevina, O.N., and Popova, O.Ya., Differences in Immune Responses, Phagocytosis and Detoxic Properties Affected by Peptide and Amino Acid Preparations, Byul. Eksper. Biol., 1995, vol. 118, no. 2, pp. 509–512.

    Google Scholar 

  2. Krichevskii, A.I., Lukash, S.A., Shugalin, V.I. et al., Aminokisloty (Amino Acids), Rostov-on-Don, 1983.

  3. Khavinson, V.Kh., Chalisova, N.I., Malinin, V.V., and Grigor’ev, E.I., Tissue-Specific Action of Peptides in the Rat Tissue Culture of Different Age, Uspekhi Gerontol., 2002, issue 9, pp. 95–100.

  4. Chalisova, N.I., Lesnyak, V.V., and Nozdrachev, A.D., Protective Influence of Amino Acids and Peptides at Combined Action with Cytostatic in the Lymphoid Tissue Culture, Dokl. RAN, 2009, vol. 434, no. 5, pp. 57–61.

    Google Scholar 

  5. Chalisova, N.I., Penniyainen, V.A., and Nozdrachev, A.D., Regulatory Action of Amino Acids in Organotypical Culture of Lymphoid Tissues of Different Mature Degree, Dokl. RAN, 2003, vol. 389, no. 2, pp. 117–119.

    CAS  Google Scholar 

  6. Chalisova, N.I., Zakutskii, A.N., Aniskina, A.I., and Nozdrachev, A.D., Influence of Arginine and Its Metabolites on Rat Myocardium in Organotypical Tissue Culture, Dokl. RAN, 2007, vol. 415, no. 2, pp. 273–276.

    Google Scholar 

  7. Chalisova, N.I., Smirnov, V.A., Ryzhak, G.A., and Kontsevaya, E.A., Influence of Encoded Amino Acids on Development of Organotypical Tissue Culture of Different Genesis of Young and Old Rats, Uspekhi Gerontol., 2010, vol. 23, no. 3, pp. 447–452.

    Google Scholar 

  8. Andrulis, I.L. and Chen P.N., Isolation of Human cDNAs for Asparagines Synthetase and Expression in Jensen Rat Sarcoma Cells, Mol. Cell. Biol., 1987, no. 7, pp. 2435–2443.

  9. Averous, J., Maurin, A.C., Bruhat, A., et al., Induction of IGFBP-1 Expression by Amino Acid Deprivation of HepG2 Human Hepatoma Cells Involves Both a Transcriptional Activation and an mRNA Stabilization Due to Its 3’UTR, FEBS Lett., 2005, vol. 579, pp. 2609–2614.

    Article  PubMed  CAS  Google Scholar 

  10. Baertl, J.M., Placko, R.P., and Graham, G.G., Serum Proteins and Plasma Free Amino Acids in Severe Malnutrition, Amer. J. Clin. Nutr., 1974, vol. 27, pp. 733–742; 918–920.

    PubMed  CAS  Google Scholar 

  11. Bhattacharyya, S.N., Habermacher, R., Martine, U., et al., Relief of microRNA-Mediated Translational Repression in Human Cells Subjected to Stress, Cell, 2006, vol. 125, pp. 1111–1124.

    Article  PubMed  CAS  Google Scholar 

  12. Bing, W., Junbao, D., Jianguang, Q., et al., L-Arginine Impacts Pulmonary Vascular Structure in Rats with an Aortocaval Shunt, J. Surg. Res., 2002, vol. 108, no. 1, pp. 20–31.

    Article  PubMed  Google Scholar 

  13. Booth, P.J., Humpherson, P.G., Watson, T.J., et al., Amino Acid Depletion and Appearance During Porcine Preimplantation Embryo Development in Vitro, Reproduction, 2005, vol. 130, no. 5, pp. 655–668.

    Article  PubMed  CAS  Google Scholar 

  14. Brasse-Lagnel, C., Lavoinne, A., and Husson, A., Control of Mammalian Gene Expression by Amino Acids, Especially Glutamine, Febs J., 2009, vol. 276, pp. 1826–1844.

    Article  PubMed  CAS  Google Scholar 

  15. Bruhat, Y., Cherasse, Y., Maurin, A., et al., ATF2 is Required for Amino Acid-Regulated Transcription by Orchestrating Specific Histone Acetylation, Nucleic Acids Res., 2007, vol. 35, pp. 1312–1321.

    Article  PubMed  CAS  Google Scholar 

  16. Bruhat, A., Jousse, C., Wang, X.Z., et al., Amino Acid Limitation Induces Expression of CHOP, a CCAAT/enhancer Binding Proteinrelated Gene, at Both Transcriptional and Post-Transcriptional Levels, J. Biol. Chem., 1997, vol. 272, pp. 17588–17593.

    Article  PubMed  CAS  Google Scholar 

  17. Chalisova, N.I. and Zakutzkii, A., Effect of amino Acids on Cell Proliferation and P53 Expression in Neonatal Rats, Cell Biol. Int., 2008, vol. 32, no. 2, pp. 1574–1577.

    Article  PubMed  CAS  Google Scholar 

  18. Chaveroux, C., Jousse, Y., Cherasse, Y., et al., Identification of a Novel Amino Acid Response Pathway Triggering ATF2 Phosphorylation in Mammals, Mol. Cell. Biol., 2009, vol. 29, pp. 6515–6526.

    Article  PubMed  CAS  Google Scholar 

  19. Chen, R.W., Qin, Z.H., and Ren, M., Regulation of c-Jun N-Terminal Kinase, p38 Kinase and AP-1 DNA Binding in Cultured Brain Neurons: Roles in Glutamate Excitotoxicity and Lithium Neuroprotection, J. Neurochem., 2003, vol. 84, no. 3, pp. 566–575.

    Article  PubMed  CAS  Google Scholar 

  20. Cherasse, Y., Chaveroux, C., Jousse, C., et al., Role of the Repressor JDP2 in the Amino Acid Regulated Transcription of CHOP, FEBS Lett., 2008, vol. 582, pp. 1537–1541.

    Article  PubMed  CAS  Google Scholar 

  21. Cherasse, Y., Maurín, A.C., Chaveroux, C., et al., The p300/CBP-Associated Factor (PCAF) is a Cofactor of ATF4 for Amino Acid-Regulated Transcription of CHOP, Nucleic Acids Res., 2007, vol. 35, pp. 5954–5965.

    Article  PubMed  CAS  Google Scholar 

  22. Chotechuang, N., Azzout-Marniche, D., Bos, C., et al., mTOR, AMPK, and GCN2 Coordinate the Adaptation of Hepatic Energy Metabolic Pathways in Response to Protein Intake in the Rat, Amer. J. Physiol., 2009, vol. 297, pp. 1313–1323.

    Google Scholar 

  23. Cid, C., Alvarez-Cermeno, J.C., Regidor, I., et al., Low Concentrations of Glutamate Induce Apoptosis in Cultured Neurons: Implications for Amyotrophic Lateral Sclerosis, J. Neurol. Sci., 2003, vol. 206, no. 1, pp. 91–95.

    Article  PubMed  CAS  Google Scholar 

  24. Deval, C., Chaveroux, C., Maurin, A.C., et al., Amino Acid Limitation Regulates the Expression of Genes Involved in Several Specific Biological Processes Through GCN2-Dependent and GCN2-Independent Pathways, Febs J., 2009, vol. 276, pp. 707–718.

    Article  PubMed  CAS  Google Scholar 

  25. Dever, T.E., Feng, L., Wek, R.C., et al., Phosphorylation of Initiation Factor 2 alpha by Protein Kinase GCN2 Mediates Genespecific Translational Control of GCN4 in Yeast, Cell., 1992, vol. 68, pp. 585–596.

    Article  PubMed  CAS  Google Scholar 

  26. Duplus, M., Glorian, C., and Forest, C., Fatty Acid Regulation of Gene Transcription, J. Biol. Chem., 2000, vol. 275, pp. 30749–30752.

    Article  PubMed  CAS  Google Scholar 

  27. Fernandez, J., Yaman, I., Sarnow, P., et al., Regulation of Internal Ribosomal Entry Site-Mediated Translation by Phosphorylation of the Translation Initiation Factor eIF2alpha, J. Biol. Chem., 2002, vol. 277, pp. 19198–19205.

    Article  PubMed  CAS  Google Scholar 

  28. Fu, Y.M., Yu, Z.X., Li, Y.Q., et al., Specific Amino Acid Dependency Regulates Invasiveness and Viability of Androgen-Independent Prostate Cancer Cells, Nutr. Cancer., 2003, vol. 45, no. 1, pp. 60–73.

    Article  PubMed  CAS  Google Scholar 

  29. Gerarde, H.W., Jones, M., and Winnick, T., Protein Synthesis and Amino Acid Turnover in Tissue Culture, J. Biol. Chem., 1966, vol. 1, pp. 51–68.

    Google Scholar 

  30. Gietzen, D.W., Neural Mechanisms in the Responses to Amino Acid Deficiency, J. Nutr., 1993, vol. 123, pp. 610–625.

    PubMed  CAS  Google Scholar 

  31. Gietzen, D.W., Amino Acid Recognition in the Central Nervous System, Boca-Raton, London, New York, Washington: CRC Press, 2000, pp. 339–357.

    Google Scholar 

  32. Gietzen, D.W., Ross, C.M., Hao, S., et al., Phosphorylation of eIF2alpha is Involved in the Signaling of Indispensable Amino Acid Deficiency in the Anterior Piriform Cortex of the Brain in Rats, J. Nutr., 2004, vol.134, pp. 717–723.

    PubMed  CAS  Google Scholar 

  33. Gong, S.S., Guerrini, L., and Basilico, C., Regulation of Asparagine Synthetase Gene Expression by Amino Acid Starvation, Mol. Cell. Biol., 1991, vol. 11, pp. 6059–6066.

    PubMed  CAS  Google Scholar 

  34. Grimaldi, P.A., Fatty Acid Regulation of Gene Expression, Curr. Opin. Clin. Nutr. Metab., 2001, vol. 4, pp. 433–437.

    Article  CAS  Google Scholar 

  35. Grimble, R.F. and Whitehead, R.G., Fasting Serum-Amino Acid Patterns in Kwashiorkor and after Administration of Different Levels of Protein, Lancet., 1970, vol. 1, pp. 123–127.

    Google Scholar 

  36. Guerrini, L., Gong, S.S., Mangasarian, K., and Basilico, C., Cis- and Trans-Acting Elements Involved in Amino Acid Regulation of Asparagine Synthetase Gene Expression, Mol. Cell. Biol., 1993, vol. 13, pp. 3202–3212.

    PubMed  CAS  Google Scholar 

  37. Guo, F.D.R. and Cavener, A., The GCN2 eIF2alpha Kinase Regulates Fatty-Acid Homeostasis in the Liver during Deprivation of an Essential Amino Acid, Cell. Metab., 2007, vol. 5, pp. 103–114.

    Article  PubMed  CAS  Google Scholar 

  38. Harding, H.P., Zhang, Y., Zeng, H., et al., An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress, Mol. Cell., 2003, vol. 11, pp. 619–633.

    Article  PubMed  CAS  Google Scholar 

  39. Hatzoglou, M., Nutritional Control of mRNA Stability is Mediated by a Conserved Au-Rich Element that Binds the Cytoplasmic Shuttling Protein HuR, J. Biol. Chem., 2002, vol. 277, pp. 41539–41546.

    Article  PubMed  Google Scholar 

  40. Hatzoglou, M., Fernandez, J., Yaman, I., and Closs, E., Regulation of Cationic Amino Acid Transport: The Story of the CAT-1 Transporter, Ann. Rev. Nutr., 2004, vol. 24, pp. 377–399.

    Article  CAS  Google Scholar 

  41. Hinnebusch, A.G., Translational Control of GCN4: An in Vivo Barometer of Initiation Factor Activity, Trends Biochem. Sci., 1994, vol. 19, pp. 409–414.

    Article  PubMed  CAS  Google Scholar 

  42. Hutson, R.G. and Kilberg, M.S., Cloning of Rat Asparagine Synthetase and Specificity of the Amino Acid-Dependent Control of Its mRNA Content, Biochem. J., 1994, vol. 304, pp. 745–750.

    PubMed  CAS  Google Scholar 

  43. Jousse, C., Averous, A., Bruhat, M., et al., Amino Acids as Regulators of Gene Expression: Molecular Mechanisms, Biochem. Biophys. Res. Commun., 2004, vol. 313, pp. 447–452.

    Article  PubMed  CAS  Google Scholar 

  44. Jousse, C., Bruhat, M., Ferrara, A., et al., Physiological Concentration of Amino Acids Regulates Insulin-Like-Growth-Factor-Binding Protein 1 Expression, Biochem. J., 1998, vol. 334, pp. 147–153.

    PubMed  CAS  Google Scholar 

  45. Kilberg, M.S., Pan, Y.X., Chen, H., et al., Nutritional Control of Gene Expression: How Mammalian Cells Respond to Amino Acid Limitation, Ann. Rev. Nutr., 2005, vol. 25, pp. 59–85.

    Article  CAS  Google Scholar 

  46. Kim, K.Y., Moon, J.I., Lee, E.J., et al., The Effect of L-Arginine, a Nitric Oxide Synthase Substrate, on Retinal Cell Proliferation in the Postnatal Rat, Dev. Neurosci., 2002, vol. 24, no. 4, pp. 313–321.

    Article  PubMed  CAS  Google Scholar 

  47. Kimball, S.R. and Jefferson, L.S., Amino Acids as Regulators of Gene Expression, Nutr. Metab. (Lond.), 2004, vol. 1, p. 3.

  48. Kimura, M. and Ogihara, M., Effects of Branched-Chain Amino Acids on DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes, Europ. J. Pharmacol., 2005, vol. 510, no. 3, pp. 167–180.

    Article  CAS  Google Scholar 

  49. Lee P.D., Conover, C.A., and Powell, D.R., Regulation and Function of Insulin-Like Growth Factor-Binding Protein-1, Proc. Soc. Exp. Biol. Med., 1993, vol. 204, pp. 4–29.

    PubMed  CAS  Google Scholar 

  50. Lu, P.D., Harding, H.P., and Ron, D., Translation Reinitiation at Alternative Open Reading Frames Regulates Gene Expression in an Integrated Stress Response, J. Cell. Biol., 2004, vol. 167, pp. 27–33.

    Article  PubMed  CAS  Google Scholar 

  51. Mellor, A.L. and Munn, D.H., IDO Expression by Dendritic Cells: Tolerance and Tryptophan Catabolism, Nat. Rev. Immunol., 2004, vol. 4, pp. 762–774.

    Article  PubMed  CAS  Google Scholar 

  52. Mellor, A.L. and Munn, D.H., Creating Immune Privilege: Active Local Suppression that Benefits Friends, but Protects Foes, Nat. Rev. Immunol., 2008, vol. 8, pp. 74–80.

    Article  PubMed  CAS  Google Scholar 

  53. Neame, K.D., Effect of Neutral Alphaand Omega-Amino Acids and Basic Alpha-Amino Acids on Uptake of L-histidine by Intestinal Mucosa, Testis, Spleen and Kidney in Vitro: A Comparison with Effect in Brain, J. Physiol., 1966, vol. 185, no. 3, pp. 627–645.

    PubMed  CAS  Google Scholar 

  54. Oehler, R. and Roth, E., Regulative Capacity of Glutamine, Curr. Opin. Clin. Nutr. Metab. Care, 2003, vol. 6, no. 3, pp. 277–282.

    PubMed  CAS  Google Scholar 

  55. Palii, S.S., Kays, C.E., Deval, C., et al., Specificity of Amino Acid Regulated Gene Expression: Analysis of Genes Subjected to Either Complete or Single Amino Acid Deprivation, Amino Acids, 2009, vol. 37, pp. 79–88.

    Article  PubMed  CAS  Google Scholar 

  56. Peng, T., Golub, T.R., and Sabatini, D.M., The Immunosuppressant Rapamycin Mimics a Starvation-Like Signal Distinct from Amino Acid and Glucose Deprivation, Mol. Cell. Biol., 2002, vol. 22, pp. 5575–5584.

    Article  PubMed  CAS  Google Scholar 

  57. Philip, R., Campbell, E., and Wheatley, D.N., Arginine Deprivation, Growth Inhibition and Tumor Cell Death: 2. Enzymatic Degradation of Arginine in Normal and Malignant Cell Cultures, Brit. J. Cancer, 2003, vol. 88, no. 4, pp. 613–623.

    Article  PubMed  CAS  Google Scholar 

  58. Proud, C.G., Amino Acids and mTOR Signalling in Anabolic Function, Biochem. Soc. Trans., 2007, vol. 35, pp. 1187–1190.

    Article  PubMed  CAS  Google Scholar 

  59. Reiling, J.H. and Sabatini, D.M., Stress and mTORture Signaling, Oncogene, 2006, vol. 25, pp. 6373–6383.

    Article  PubMed  CAS  Google Scholar 

  60. Straus, D.S., Burke, E.J., and Marten, N.W., Induction of Insulin-Like Growth Factor Binding Protein-1 Gene Expression in Liver of Protein-Restricted Rats and in Rat Hepatoma Cells Limited for a Single Amino Acid, Endocrinology, 1993, vol. 132, pp. 1090–1100.

    Article  PubMed  CAS  Google Scholar 

  61. Sundrud, M.S., Koralov, S.B., Feuerer, M., et al., Halofuginone Inhibits TH17 Cell Differentiation by Activating the Amino Acid Starvation Response, Science, 2009, vol. 324, pp. 1334–1338.

    Article  PubMed  CAS  Google Scholar 

  62. Suschek, C.V., Schnirr, O., Hemmrich, K., et al., Critical Role of L-arginine in Endothelial Cell Survival During Oxidative Stress, Circulation, 2003, vol. 107, no. 20, pp. 2607–2014.

    PubMed  CAS  Google Scholar 

  63. Sylvester, S.L., Rhys, C.M., Luethy-Martindale, J.D., and Holbrook, N.J., Induction of GADD153, a CCAAT/Enhancer-Binding Protein (C/EBP)-Related Gene, During the Acute Phase Response in Rats, Evidence for the Involvement of C/EBPs in Regulating Its Expression, J. Biol. Chem., 1994, vol. 269, pp. 20119–20125.

    PubMed  CAS  Google Scholar 

  64. Towle, H.C., Metabolic Regulation of Gene Transcription in Mammals, J. Biol. Chem., 1995, vol. 270, pp. 23235–23238.

    PubMed  CAS  Google Scholar 

  65. Trulsson, L., Sandström, P., Sundqvist, T., et al., The Influence of a Load of L-arginine on Serum Amino Acids and Pancreatic Apoptosis/Proliferation and ATP Levels in the Rat, Pancreas., 2004, vol. 29, no. 4, pp. 113–120.

    Article  Google Scholar 

  66. Vattem, K.M. and Wek, R.C., Reinitiation Involving Upstream ORFs Regulates ATF4 mRNA Translation in Mammalian Cells, Proc. Natl. Acad. Sci. USA, 2004, vol. 101, pp. 11269–11274.

    Article  PubMed  CAS  Google Scholar 

  67. Watatani, Y., Ichikawa, K., Nakanishi, N., et al., Stress-Induced Translation of ATF5 mRNA is Regulated by the 5′-Untranslated Region, J. Biol. Chem., 2008, vol. 283, pp. 2543–2553.

    Article  PubMed  CAS  Google Scholar 

  68. Yaman, J., Fernandez, H., Liu, C., et al., The Zipper Model of Translational Control: A Small Upstream ORF is the Switch that Controls Structural Remodeling of an mRNA Leader, Cell, 2003, vol. 113, pp. 519–531.

    Article  PubMed  CAS  Google Scholar 

  69. Young, V.R., El-Khoury, A.E., Melchor, S., and Castillo, L., The Biochemistry and Physiology of Protein and Amino Acid Metabolism, with Reference to Protein Nutrition, in Protein Metabolism during Infancy, Niels, C.R.R., Ed., New York: Nestec Ltd., Press Ltd., 1994, p. 28.

    Google Scholar 

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Authors and Affiliations

  1. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Nab. Makarova, St. Petersburg, 199034, Russia

    N. I. Chalisova & A. V. Komashnya

  2. St. Petersburg Institute of Bioregulation and Gerontology, Northwest Branch, Russian Academy of Medical Sciences, 3 pr. Dinamo, St. Petersburg, 197110, Russia

    E. A. Kontsevaya & M. A. Voytsehovskaya

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  1. N. I. Chalisova
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  2. E. A. Kontsevaya
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  3. M. A. Voytsehovskaya
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  4. A. V. Komashnya
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Original Russian Text © N.I. Chalisova, E.A. Kontsevaya, M.A. Voytsehovskaya, A.V. Komashnya, 2011, published in Uspekhi Gerontologii, 2011, Vol. 24, No. 2, pp. 189–197.

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Chalisova, N.I., Kontsevaya, E.A., Voytsehovskaya, M.A. et al. The regulatory effects of coded amino acids on basic cellular processes in young and old animals. Adv Gerontol 2, 10–18 (2012). https://doi.org/10.1134/S2079057012010067

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