Biochemistry (Moscow)

, Volume 77, Issue 11, pp 1277–1284

Cellular acidosis inhibits assembly, disassembly, and motility of stress granules

  • E. M. Chudinova
  • E. S. Nadezhdina
  • P. A. Ivanov
Article

Abstract

Stress granules (SGs) are large ribonucleoprotein (RNP)-containing particles that form in cytoplasm in response to a variety of acute changes in the cellular environment. One of the general parameters of the cell environment is pH. In some diseases, as well as in muscle fatigue, tissue acidosis occurs, leading to decrease in intracellular pH. Here we studied whether decrease in pH causes the formation of SGs in cultured animal cells, whether it affects the formation of the SGs under the action of arsenite and, if such effects occur, what are the mechanisms of the influence of acidosis. Acidosis was simulated by decreasing the pH of the culture medium, which acidified the cytoplasm. We found that medium acidification to pH 6.0 in itself did not cause formation of SGs in cells. Moreover, acidification prevented the formation of SGs under treatment with sodium arsenite or sodium arsenite together with the proteasome inhibitor MG132, and it inhibited the dissociation of preformed SGs under the influence of cycloheximide. We established that pH decrease did not affect the phosphorylation of eIF2α that occurs under the action of sodium arsenite, and even caused such phosphorylation by itself. We also found that the velocity of SG motion in cytoplasm at acidic pH was very low, and the mobile fraction of SG-incorporated PABP protein revealed by FRAP was decreased. We suppose that acidic pH impairs biochemical processes favoring assembly of RNPs in stress conditions and RNP dissociation on the termination of stress. Thus, in acidosis the reaction of the cellular translation apparatus to stress is modified.

Key words

RNP cytoplasm pH sodium arsenite FRAP microtubule 

Abbreviations

FRAP

fluorescence recovery after photobleaching

RNP

ribonucleoprotein

SG

stress granule

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References

  1. 1.
    Rehncrona, S. (1985) Ann. Emerg. Med., 14, 770–776.PubMedCrossRefGoogle Scholar
  2. 2.
    Kraig, R. P., and Chestler, M. J. (1990) Cerebr. Blood Flow Metab., 10, 104–114.CrossRefGoogle Scholar
  3. 3.
    Sahlin, K., Harris, R. C., and Hultman, E. (1975) Biochem. J., 152, 173–180.PubMedGoogle Scholar
  4. 4.
    Anderson, P., and Kedersha, N. (2006) J. Cell Biol., 172, 803–808.PubMedCrossRefGoogle Scholar
  5. 5.
    Buchan, J. R., and Parker, R. (2009) Mol. Cell, 36, 932–941.PubMedCrossRefGoogle Scholar
  6. 6.
    Kedersha, N., Chen, S., Gilks, N., Li, W., Miller, I. J., Stahl, J., and Anderson, P. (2002) Mol. Biol. Cell, 13, 195–210.PubMedCrossRefGoogle Scholar
  7. 7.
    Farrell, P. J., Balkow, K., Hunt, T., Jackson, R. J., and Trachsel, H. (1977) Cell, 11, 187–200.PubMedCrossRefGoogle Scholar
  8. 8.
    Kedersha, N., Cho, M., Li, W., Yacono, P., Chen, S., Gilks, N., Golan, D., and Anderson, P. (2000) J. Cell Biol., 151, 1257–1268.PubMedCrossRefGoogle Scholar
  9. 9.
    Loschi, M., Leishman, C. C., Berardone, N., and Boccaccio, G. L. (2009) J. Cell Sci., 122, 3973–3982.PubMedCrossRefGoogle Scholar
  10. 10.
    Nadezhdina, E. S., Lomakin, A. J., Shpilman, A. A., Chudinova, E. M., and Ivanov, P. A. (2010) Biochim. Biophys. Acta, 1803, 361–371.PubMedCrossRefGoogle Scholar
  11. 11.
    Bartoli, K. M., Bishop, D. L., and Saunders, W. S. (2011) Int. J. Cell Biol., 2011, 939848.PubMedGoogle Scholar
  12. 12.
    Ivanov, P. A., Chudinova, E. M., and Nadezhdina, E. S. (2003) Exp. Cell Res., 290, 227–233.PubMedCrossRefGoogle Scholar
  13. 13.
    Kolobova, E., Efimov, A., Kaverina, I., Rishi, A. K., Schrader, J. W., Ham, A. J., Larocca, M. C., and Goldenring, J. R. (2009) Exp. Cell Res., 315, 542–555.PubMedCrossRefGoogle Scholar
  14. 14.
    Dorovkov, M. V., Pavur, K. S., Petrov, A. N., and Ryazanov, A. G. (2002) Biochemistry, 41, 13444–13450.PubMedCrossRefGoogle Scholar
  15. 15.
    Shanins, N. A., Ivanov, P. A., Chudinova, E. M., Severin, F. F., and Nadezhdina, E. S. (2001) Mol. Biol. (Moscow), 35, 638–646.Google Scholar
  16. 16.
    Anderson, P., and Kedersha, N. J. (2002) Cell Sci., 115, 3227–3234.Google Scholar
  17. 17.
    Isozaki, U., Mitch, W. E., England, B. K., and Price, S. R. (1996) Proc. Natl. Acad. Sci. USA, 93, 1967–1971.PubMedCrossRefGoogle Scholar
  18. 18.
    Chernov, K. G., Barbet, A., Hamon, L., Ovchinnikov, L. P., Curmi, P. A., and Pastre, D. (2009) J. Biol. Chem., 284, 36569–36580.PubMedCrossRefGoogle Scholar
  19. 19.
    Vantelon, N., Rioux-Bilan, A., Ingrand, S., Pain, S., Page, G., Guillard, O., Barrier, L., Piriou, A., and Fauconneau, B. (2007) Eur. J. Neurosci., 26, 689–700.PubMedCrossRefGoogle Scholar
  20. 20.
    Carlberg, U., Nilsson, A., and Nygard, O. (1990) Eur. J. Biochem., 191, 639–645.PubMedCrossRefGoogle Scholar
  21. 21.
    Gilks, N., Kedersha, N., Ayodele, M., Shen, L., Stoecklin, G., Dember, L. M., and Anderson, P. (2004) Mol. Biol. Cell., 15, 5383–5398.PubMedCrossRefGoogle Scholar
  22. 22.
    Kwon, S., Zhang, Y., and Matthias, P. (2007) Genes Dev., 21, 3381–3394.PubMedCrossRefGoogle Scholar
  23. 23.
    Fujimura, K., Katahira, J., Kano, F., Yoneda, Y., and Murata, M. (2009) Biochim. Biophys. Acta, 1793, 1728–1737.PubMedCrossRefGoogle Scholar
  24. 24.
    Cooper, J. R., and Wordeman, L. (2009) Curr. Opin. Cell Biol., 21, 68–73.PubMedCrossRefGoogle Scholar
  25. 25.
    Ohn, T., Kedersha, N., Hickman, T., Tisdale, S., and Anderson, P. (2008) Nat. Cell Biol., 10, 1224–1231.PubMedCrossRefGoogle Scholar
  26. 26.
    Ohn, T., and Anderson, P. (2010) Wiley Interdiscip. Rev. RNA, 1, 486–493.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2012

Authors and Affiliations

  • E. M. Chudinova
    • 1
  • E. S. Nadezhdina
    • 1
    • 2
  • P. A. Ivanov
    • 2
    • 3
  1. 1.Institute of Protein ResearchRussian Academy of SciencesPushchino, Moscow RegionRussia
  2. 2.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  3. 3.Biological FacultyLomonosov Moscow State UniversityMoscowRussia

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