Biochemistry (Moscow)

, 76:571 | Cite as

Protective effect of L-arginine administration on proteins of unloaded m. soleus

  • Yu. N. Lomonosova
  • G. R. Kalamkarov
  • A. E. Bugrova
  • T. F. Shevchenko
  • N. L. Kartashkina
  • E. A. Lysenko
  • V. I. Shvets
  • T. L. NemirovskayaEmail author


Cytoskeletal and contractile proteins degenerate during functional unloading of muscle. The ratio of myosin heavy chain (MHC) expression changes simultaneously. We have supposed that NO can be a signal molecule related to the regulation of protein metabolism upon muscle unloading. To test this hypothesis, Wistar rats underwent functional unloading for 14 days without and with peroral administration of L-arginine (500 mg/kg) as NO precursor. Significant decreases in m. soleus mass, NO, nNOS, dystrophin, Hsp90, p-S6K, and type I MHC mRNA contents were found in the group of animals with unloading without preparation compared to those in control and in the group with unloading and administration of L-arginine; at the same time, increased contents of atrogin-1/MAFbx and MuRF-1 (p < 0.05) were found. No difference in the IGF-1 mRNA content between all three groups was found. Atrophy was significantly less pronounced in the group with unloading and L-arginine administration compared to that without the amino acid, and no destruction of cytoskeletal proteins was observed. We conclude that administration of L-arginine upon functional unloading decreases the extent of m. soleus atrophy, prevents the decrease in it of type I MHC mRNA, and blocks destructive changes in some cytoskeletal proteins. Such effect can be due to the absence of increase in this group of the content of some ubiquitin ligases and decreased intensity of the p70S6 kinase synthesis marker.

Key words

m. soleus atrophy L-arginine administration cytoskeletal proteins NO nNOS Hsp90 E3 ligases P70/S6k IGF-1 MHC 



atrogin-1/Muscle Atrophy F-box


cross sectional area




glyceraldehyde-3-phosphate dehydrogenase


90β heat shock proteins


insulin-like growth factor 1


muscle fiber


myosin heavy chain


mammalian target of rapamycin


muscle-specific RING finger protein 1


neuronal NO synthase


p70S6 kinase


phosphorylated form of p70S6 kinase


  1. 1.
    Chopard, A., Francoise, P., and Marini, J.-F. (2001) Am. J. Physiol. Regul. Integr. Comp. Physiol., 280, 323–330.Google Scholar
  2. 2.
    Thomason, D. B., Biggs, R. B., and Booth, F. W. (1989) Am. J. Physiol. Regul. Integr. Comp. Physiol., 257, 300–305.Google Scholar
  3. 3.
    Thomason, D. B., and Booth, F. W. (1990) J. Appl. Physiol., 68, 1–12.PubMedCrossRefGoogle Scholar
  4. 4.
    Shenkman, B. S., and Nemirovskaya, T. L. (2008) J. Muscle Res. Cell Motil., 29, 221–230.PubMedCrossRefGoogle Scholar
  5. 5.
    Ingalls, C. P., Warren, G. L., and Armstrong, R. B. (1999) J. Appl. Physiol., 87, 386–390.PubMedGoogle Scholar
  6. 6.
    Barton, E. R., Morris, L., Kawana, M., Bish, L. T., and Toursel, T. (2005) Muscle Nerve, 32, 751–760.PubMedCrossRefGoogle Scholar
  7. 7.
    Vincent, V., Sebrie, C., Matecki, S., Yu, H., Gillet, B., Ramonatxo, M., Israel, M., and de la Porte, S. (2005) Neurobiol. Dis., 20, 123–130.CrossRefGoogle Scholar
  8. 8.
    Timothy, K. J., and Tidball, J. G. (2000) Am. J. Physiol. Cell Physiol., 279, 806–812.Google Scholar
  9. 9.
    Salanova, M., Schiffl, G., Puttmann, B., Schoser, B. G., and Blottner, D. (2008) J. Anat., 212, 306–318.PubMedCrossRefGoogle Scholar
  10. 10.
    Tidball, J. G., Lavergne, E., Lau, K. S., Spencer, M. J., Stull, J. T., and Wehling, M. (1998) Am. J. Physiol. (Cell Physiol. 44), 275, 260–266.Google Scholar
  11. 11.
    Cohen, S., Brault, J. J., Gygi, S. P., Glass, D. J., Valenzuela, D. M., Gartner, C., Latres, E., and Goldberg, A. L. (2009) J. Cell Biol., 185, 1083–1095.PubMedCrossRefGoogle Scholar
  12. 12.
    Morey-Holton, E. R., and Globus, R. K. (2002) J. Appl. Physiol., 92, 1367–1377.PubMedCrossRefGoogle Scholar
  13. 13.
    Lomonosova, Yu. N., Zheleznyakova, A. V., Bugrova, A. E., Zhiryakova, A. V., Kalamkarov, G. R., and Nemirovskaya, T. L. (2009) Biofizika, 54, 515–521.PubMedGoogle Scholar
  14. 14.
    Vanin, A. F., Huisman, A., and van Faassen, E. E. (2002) Meth. Enzymol., 359, 27–42.PubMedCrossRefGoogle Scholar
  15. 15.
    Obolenskaya, M. Yu., Vanin, A. F., Mordvintcev, P. I., Molsch, A., and Decker, K. (1994) Biochem. Biophys. Res. Commun., 202, 571–576.PubMedCrossRefGoogle Scholar
  16. 16.
    Soti, C., Nagy, E., Giricz, Z., Vigh, L., Csermely, P., and Ferdinandy, P. (2005) British J. Pharmacol., 146, 769–780.CrossRefGoogle Scholar
  17. 17.
    Balon, T. W., and Nadler, J. L. (1994) J. Appl. Physiol., 77, 2519–2521.PubMedGoogle Scholar
  18. 18.
    Pye, D., Palomero, J., Kabayo, T., and Jackson, M. J. (2007) J. Physiol., 15, 309–318.CrossRefGoogle Scholar
  19. 19.
    Brennan, M. H., Mitchell, B. M., Sood, S. G., Webb, R. C., and Venema, R. C. (2008) Eur. J. Appl. Physiol., 104, 795–802.Google Scholar
  20. 20.
    Sakurai, T., Fujita, Y., Ohto, E., Oguro, A., and Atomi, Y. (2005) FASEB J., 19, 1199–1201.PubMedGoogle Scholar
  21. 21.
    Ishihara, A., Fujino, H., Nagatomo, F., Takeda, I., and Ohira, Y. (2008) J. Physiol. Sci., 58, 413–417.PubMedCrossRefGoogle Scholar
  22. 22.
    Averna, M., Stifanese, R., de Tullio, R., Salamino, F., Pontremoli, S., and Melloni, E. (2008) FEBS J., 275, 2501–2511.PubMedCrossRefGoogle Scholar
  23. 23.
    Song, Y., Zweier, J. L., and Xia, Y. (2001) Biochem. J., 355, 357–360.PubMedCrossRefGoogle Scholar
  24. 24.
    Song, Y., Zweier, J. L., and Xia, Y. (2001) Am. J. Physiol. Cell Physiol., 281, 1819–1824.Google Scholar
  25. 25.
    Vermaelen, M., Sirvent, P., Raynaud, F., Astier, C., Mercier, J., Lacampagne, A., and Cazorla, O. (2007) Am. J. Physiol. Cell Physiol., 292, 1723–1731.CrossRefGoogle Scholar
  26. 26.
    Koh, T. J., and Tidball, J. G. (2000) Am. J. Physiol. Cell Physiol., 279, 806–812.Google Scholar
  27. 27.
    Chockalingam, P. S., Cholera, R., Oak, S. A., Zheng, Y., Jarrett, H. W., and Thomason, D. B. (2002) Am. J. Physiol. Cell Physiol., 283, 500–511.Google Scholar
  28. 28.
    Dapp, C., Schmutz, S., Hoppeler, H., and Fluck, M. (2004) Physiol. Genom., 20, 97–107.CrossRefGoogle Scholar
  29. 29.
    Enns, D. L., Raastad, T., Ugelstad, I., and Belcastro, A. N. (2007) Eur. J. Appl. Physiol., 100, 445–455.PubMedCrossRefGoogle Scholar
  30. 30.
    Giger, J. M., Bodell, P. W., Zeng, M., Baldwin, K. M., and Haddad, F. (2009) J. Appl. Physiol., 107, 1204–1212.PubMedCrossRefGoogle Scholar
  31. 31.
    Wagatsuma, A., Fujimoto, K., and Yamada, S. (2002) Scand. J. Med. Sci. Sports, 12, 26–30.PubMedCrossRefGoogle Scholar
  32. 32.
    Chopard, A., Arrighi, N., Carnino, A., and Marini, J. F. (2005) FASEB J., 19, 1722–1724.PubMedGoogle Scholar
  33. 33.
    Jackman, R. W., and Kandarian, S. C. (2004) Am. J. Physiol. Cell Physiol., 287, 834–843.CrossRefGoogle Scholar
  34. 34.
    Dupont-Versteegden, E. E., Fluckey, J. D., Knox, M., Gaddy, D., and Peterson, C. A. (2006) J. Appl. Physiol., 101, 202–212.PubMedCrossRefGoogle Scholar
  35. 35.
    Reid, M. B. (2005) Am. J. Physiol. Regul. Integr. Comp. Physiol., 288, 1423–1431.CrossRefGoogle Scholar
  36. 36.
    Pratt, W. B., Morishima, Y., and Osawa, Y. (2008) J. Biol. Chem., 283, 22885–22889.PubMedCrossRefGoogle Scholar
  37. 37.
    Bodine, S. C., Stitt, T. N., Gonzalez, M., Kline, W. O., Stover, G. L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J. C., Glass, D. J., and Yancopoulos, G. D. (2001) Nat. Cell Biol., 3, 1014–1029.PubMedCrossRefGoogle Scholar
  38. 38.
    Gwag, T., Lee, K., Ju, H., Shin, H., and Lee, J. W. (2009) Cell Physiol. Biochem., 24, 537–546.PubMedCrossRefGoogle Scholar
  39. 39.
    Song, Y. H., Godard, M., Li, Y., Richmond, S. R., Rosenthal, N., and Delafontaine, P. (2005) J. Invest. Med., 53, 135–142.CrossRefGoogle Scholar
  40. 40.
    Awedea, B., Thissenb, J.-P., Gaillya, P., and Lebacq, J. (1999) FEBS Lett., 461, 263–267.CrossRefGoogle Scholar
  41. 41.
    Lori, S. W., Smith, J. D., and Criswell, D. S. (2002) J. Appl. Physiol., 92, 2005–2011.Google Scholar
  42. 42.
    Drenning, J. A., Lira, V. A., Simmons, C. G., Soltow, Q. A., Sellman, J. E., and Criswell, D. S. (2008) Am. J. Physiol. Cell Physiol., 294, 1088–1095.CrossRefGoogle Scholar
  43. 43.
    Chin, E. R. (2005) J. Appl. Physiol., 99, 414–423.PubMedCrossRefGoogle Scholar
  44. 44.
    Peng, H.-M., Morishima, Y., Clapp, K. M., Lau, M., Pratt, W. B., and Osawa, Y. (2009) Biochemistry, 48, 8483–8490.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • Yu. N. Lomonosova
    • 1
    • 2
  • G. R. Kalamkarov
    • 3
  • A. E. Bugrova
    • 3
  • T. F. Shevchenko
    • 3
  • N. L. Kartashkina
    • 4
  • E. A. Lysenko
    • 4
  • V. I. Shvets
    • 2
  • T. L. Nemirovskaya
    • 1
    • 4
    Email author
  1. 1.Faculty of Basic MedicineLomonosov Moscow State UniversityMoscowRussia
  2. 2.Lomonosov Moscow Academy of Fine Chemical TechnologyMoscowRussia
  3. 3.Emanuel Institute of Biochemical PhysicsRussian Academy of SciencesMoscowRussia
  4. 4.Institute for Bio-Medical ProblemsRussian Academy of SciencesMoscowRussia

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