Biochemistry (Moscow)

, Volume 77, Issue 2, pp 208–216 | Cite as

Role of NO-synthase in regulation of protein metabolism of stretched rat m. soleus muscle during functional unloading

  • Yu. N. Lomonosova
  • G. R. Kalamkarov
  • A. E. Bugrova
  • T. F. Shevchenko
  • N. L. Kartashkina
  • E. A. Lysenko
  • B. S. Shenkman
  • T. L. NemirovskayaEmail author


Gravitational unloading causes atrophy of muscle fibers and can lead to destruction of cytoskeletal and contractile proteins. Along with the atrophic changes, unloaded muscle frequently demonstrates significant shifts in the ratio of muscle fibers expressing fast and slow myosin heavy chain isoforms. Stretching of the m. soleus during hindlimb suspension prevents its atrophy. We supposed that neuronal NO-synthase (NOS) (which is attached to membrane dystrophin-sarcoglycan complex) can contribute to maintenance of protein metabolism in the muscle and prevent its atrophy when m. soleus is stretched. To test this hypothesis, we used Wistar rats (56 animals) in experiments with hindlimb suspension during 14 days. The group of hindlimb suspended rats with stretched m. soleus was injected with L-NAME to block NOS activity. We found that m. soleus mass and its protein content in hindlimb-suspended rats with stretched m. soleus were preserved due to prevention of protein degradation. NOS is involved in maintenance of expression of some muscle proteins. Proliferation of satellite cells in stretched m. soleus may be due to nNOS activity, but maintenance of muscle mass upon stretching is regulated not by NOS alone.

Key words

m. soleus unloading m. soleus stretching L-NAME cytoskeletal proteins nNOS Hsp90 E3 ligase p70S6K 



atrogin-1/Muscle Atrophy F-box


cross section area




glyceraldehyde-3-phosphate dehydrogenase


hindlimb-suspended rats


hindlimb-suspended rats with stretched m. soleus


hindlimb-suspended rats with stretched m. soleus and L-NAME injection


90β heat shock proteins


N-nitro-L-arginine methyl ester hydrochloride


muscle fiber


myosin heavy chain(s)


mammalian target of rapamycin


muscle-specific RING finger protein 1


(neuronal) NO synthase


p70S6 kinase


phosphorylated form of p70S6 kinase


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  1. 1.
    Falempin, M., and Mounier, Y. (1998) Acta Astronautica, 42, 489–501.PubMedCrossRefGoogle Scholar
  2. 2.
    Booth, F. W., and Thomason, D. B. (1973) Am. J. Physiol., 23, 404–406.Google Scholar
  3. 3.
    Paul, L., Goldspink, G., and Goldspink, D. F. (1986) J. Appl. Physiol., 61, 173–179.Google Scholar
  4. 4.
    Jaspers, S. R., Fagan, J. M., Satarug, S., Cook, P. H., and Tischler, M. E. (1988) Muscle Nerve, 11, 458–466.PubMedCrossRefGoogle Scholar
  5. 5.
    Koh, T. J., and Tidball, J. G. (2000) Am. J. Physiol. Cell Physiol., 279, 806–812.Google Scholar
  6. 6.
    Shenkman, B. S., and Nemirovskaya, T. L. (2008) J. Muscle Res. Cell Motil., 29, 221–230.PubMedCrossRefGoogle Scholar
  7. 7.
    Ingalls, C. P., Warren, G. L., and Armstrong, R. B. (1999) J. Appl. Physiol., 87, 386–390.PubMedGoogle Scholar
  8. 8.
    Murphy, R. M., Verburg, E., and Lamb, G. D. (2006) J. Physiol., 576, 595–612.PubMedCrossRefGoogle 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. (1999) Am. J. Physiol., 275, 260–266.Google Scholar
  11. 11.
    Lomonosova, Yu. N., Kalamkarov, G. R., Bugrova, A. E., Shevchenko, T. F., Kartashkina, N. L., Lysenko, E. A., Shvets, V. I., and Nemirovskaya, T. L. (2011) Biochemistry (Moscow), 76, 571–580.CrossRefGoogle Scholar
  12. 12.
    Pye, D., Palomero, J., Kabayo, T., and Jackson, M. J. (2007) J. Physiol., 581, 309–318.PubMedCrossRefGoogle Scholar
  13. 13.
    Zhang, J. S., Kraus, W. E., and Truskey, G. A. (2004) Am. J. Physiol. Cell Physiol., 287, 292–299.CrossRefGoogle Scholar
  14. 14.
    Sellman, J. E., DeRuisseau, K. C., Betters, J. L., Lira, V. A., Soltow, Q. A., Selsby, J. T., and Criswell, D. S. (2006) J. Appl. Physiol., 100, 258–265.PubMedCrossRefGoogle Scholar
  15. 15.
    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
  16. 16.
    Wang, X. D., Kawano, F., Matsuoka, Y., Fukunaga, K., Terada, M., Sudoh, M., Ishihara, A., and Ohira, Y. (2006) Am. J. Physiol. Cell. Physiol., 290, C981–C989.PubMedCrossRefGoogle Scholar
  17. 17.
    Kawano, F., Matsuoka, Y., Oke, Y., Higo, Y., Terada, M., Wang, X. D., Nakai, N., Fukuda, H., Imajoh-Ohmi, S., and Ohira, Y. (2007) Am. J. Physiol. Cell Physiol., 293, 35–44.CrossRefGoogle Scholar
  18. 18.
    Anderson, J. E. (2000) Mol. Biol. Cell, 11, 1859–1874.PubMedGoogle Scholar
  19. 19.
    Morey-Holton, E. R., and Globus, R. K. (2002) J. Appl. Physiol., 92, 1367–1377.PubMedCrossRefGoogle Scholar
  20. 20.
    Riley, D. A., Slocum, G. R., Bain, J. L., Sedlak, F. R., Sowa, T. E., and Mellender, J. W. (1990) J. Appl. Physiol., 69, 58–66.PubMedGoogle Scholar
  21. 21.
    Obolenskaya, M. Yu., Vanin, A. F., Mordvintcev, P. I., Molsch, A., and Decker, K. (1994) Biophys. Biochem. Res. Commun., 202, 571–576.CrossRefGoogle Scholar
  22. 22.
    Vanin, A. F., Huisman, A., and van Faassen, E. E. (2002) Methods Enzymol., 359, 27–42.PubMedCrossRefGoogle Scholar
  23. 23.
    Koh, T. J., and Tidball, J. G. (1999) J. Physiol., 519, 189–196.PubMedCrossRefGoogle Scholar
  24. 24.
    Dapp, C., Schmutz, S., Hoppeler, H., and Fluck, M. (2004) Physiol. Genom., 20, 97–107.CrossRefGoogle Scholar
  25. 25.
    Enns, D. L., Raastad, T., Ugelstad, I., and Belcastro, A. N. (2007) Eur. J. Appl. Physiol., 100, 445–455.PubMedCrossRefGoogle Scholar
  26. 26.
    Chopard, A., Pons, F., and Marini, J. F. (2001) Am. J. Physiol. Regul. Integr. Comp. Physiol., 280, 323–330.Google Scholar
  27. 27.
    Chopard, A., Arrighi, N., Carnino, A., and Marini, J. F. (2005) FASEB J., 19, 1722–1724.PubMedGoogle Scholar
  28. 28.
    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
  29. 29.
    Song, Y., Zweier, J. L., and Xia, Y. (2001) Biochem. J., 355, 357–360.PubMedCrossRefGoogle Scholar
  30. 30.
    Averna, M., Stifanese, R., De Tullio, R., Salamino, F., Pontremoli, S., and Melloni, E. (2008) FEBS J., 275, 2501–2511.PubMedCrossRefGoogle Scholar
  31. 31.
    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
  32. 32.
    Harris, M. B., Mitchell, B. M., Sood, S. G., Webb, R. C., and Venema, R. C. (2008) Eur. J. Appl. Physiol., 104, 795–802.PubMedCrossRefGoogle 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.
    Zhang, S. J., Kraus, W. E., and Truskey, G. A. (2004) Am. J. Physiol. Cell. Physiol., 287, 292–299.CrossRefGoogle Scholar
  40. 40.
    Koh, T. J., and Tidball, J. G. (1999) J. Physiol., 519, 189–196.PubMedCrossRefGoogle Scholar
  41. 41.
    Anderson, J. E., and Ashley, C. W. (2004) Canad. J. Physiol. Pharmacol., 82, 300–310.CrossRefGoogle Scholar
  42. 42.
    Thomason, D. B., Biggs, R. B., and Booth, F. W. (1989) Am. J. Physiol. Regul. Integr. Comp. Physiol., 257, 300–305.Google Scholar
  43. 43.
    Smith, L. W., Smith, J. D., and Criswell, D. S. (2002) J. Appl. Physiol., 92, 2005–2011.PubMedGoogle Scholar
  44. 44.
    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
  45. 45.
    Chin, E. R. (2005) J. Appl. Physiol., 99, 414–423.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2012

Authors and Affiliations

  • Yu. N. Lomonosova
    • 1
    • 2
  • G. R. Kalamkarov
    • 3
  • A. E. Bugrova
    • 3
  • T. F. Shevchenko
    • 3
  • N. L. Kartashkina
    • 2
  • E. A. Lysenko
    • 2
  • B. S. Shenkman
    • 2
  • T. L. Nemirovskaya
    • 1
    • 2
    Email author
  1. 1.Faculty of Basic MedicineLomonosov Moscow State UniversityMoscowRussia
  2. 2.Institute for Bio-Medical ProblemsRussian Academy of SciencesMoscowRussia
  3. 3.Emanuel Institute of Biochemical PhysicsRussian Academy of SciencesMoscowRussia

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