[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Skip to main content
Springer Nature Link
Log in

Changes in the receptor function of Na,K-ATPase during hypoxia and ischemia

  • Molecular Cell Biology
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Na,K-ATPase maintains sodium and potassium homeostasis. It is the only known receptor for cardiotonic steroids such as ouabain. Binding of ouabain to Na,K-ATPase leads to the activation of Src kinase and the subsequent initiation of intracellular signaling pathways, including the induction of apoptosis. Changes in Na,K-ATPase activity is one of the earliest responses to hypoxia and is most critical for cell survival. However, it is not known how the hypoxia affects the functioning of Na,K-ATPase as a receptor. We have shown that, under the conditions of hypoxia and ischemia, ouabain is less toxic for murine fibroblast cells (SC-1 cell line) and ouabain does not cause an increase in the level of reactive oxygen species, which is typically observed at 20% pO2. Under hypoxia, the treatment of cells with ouabain also does not lead to the activation of Na,K-ATPase-associated Src kinase. Thus, at low oxygen content, the receptor function of Na,K-ATPase is altered, and cells become less sensitive to cardiotonic steroids. The decrease in sensitivity to cardiotonic steroids, which is evident at hypoxic conditions, should be taken into account in clinical practice. At the same time, in the presence of ouabain the cells are less sensitive to hypoxia, which indicates that cardiotonic steroids can be protective in acute ischemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CTS:

cardiotonic steroid

ROS:

reactive oxygen species

PBS:

phosphate buffered saline

DMSO:

dimethyl sulfoxide

References

  1. Kaplan J.H. 2002. Biochemistry of Na, K-ATPase. Annu. Rev. Biochem. 71, 511–535.

    Article  CAS  PubMed  Google Scholar 

  2. Reinhard L., Tidow H., Clausen M.J., Nissen P. 2013. Na+, K+-ATPase as a docking station: protein-protein complexes of the Na+, K+-ATPase. Cell. Mol. Life Sci. 70, 205–222.

    Article  CAS  PubMed  Google Scholar 

  3. Laursen M., Yatime L., Nissen P., Fedosova N.U. 2013. Crystal structure of the high-affinity Na+, K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site. Proc. Natl. Acad. Sci. U. S. A. 110, 10958–10963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cornelius F., Kanai R., Toyoshima C. 2013. A structural view on the functional importance of the sugar moiety and steroid hydroxyls of cardiotonic steroids in binding to Na, K-ATPase. J. Biol. Chem. 288, 6602–6616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kharkevich D.A. 2010. Farmakologiya (Pharmacology). Moscow: GEOTAR-Media.

    Google Scholar 

  6. De Angelis C., Haupert G.T., Jr. 1998. Hypoxia triggers release of an endogenous inhibitor of Na+, K+-ATPase from midbrain and adrenal. Am. J. Physiol. 274, F182–F188.

    PubMed  Google Scholar 

  7. Ludens J.H., Clark M.A., Du Charme D.W., Harris D.W., Lutzke B.S., Mandel F., Mathews W.R., Sutter D.M., Hamlyn J.M. 1991. Purification of an endogenous digitalislike factor from human plasma for structural analysis. Hypertension. 17, 923–929.

    Article  CAS  PubMed  Google Scholar 

  8. Fedorova O.V., Doris P.A., Bagrov A.Y. 1998. Endogenous marinobufagenin-like factor in acute plasma volume expansion. Clin. Exp. Hypertens. 20, 581–591.

    Article  CAS  PubMed  Google Scholar 

  9. Haas M., Wang H., Tian J., Xie Z. 2002. Src-mediated inter-receptor cross-talk between the Na+/K+-ATPase and the epidermal growth factor receptor relays the signal from ouabain to mitogen-activated protein kinases. J. Biol. Chem. 277, 18694–18702.

    Article  CAS  PubMed  Google Scholar 

  10. Knock G.A., Snetkov V.A., Shaifta Y., Drndarski S., Ward J.P., Aaronson P.I. 2008. Role of src-family kinases in hypoxic vasoconstriction of rat pulmonary artery. Cardiovasc. Res. 80, 453–462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. MacAuley A., Cooper J.A. 1989. Structural differences between repressed and derepressed forms of p60c-src. Mol. Cell. Biol. 9, 2648–2656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xu W., Harrison S.C., Eck M.J. 1997. Three-dimensional structure of the tyrosine kinase c-Src. Nature. 385, 595–602.

    Article  CAS  PubMed  Google Scholar 

  13. Cowan-Jacob S.W., Fendrich G., Manley P.W., Jahnke W., Fabbro D., Liebetanz J., Meyer T. 2005. The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation. Structure. 13, 861–871.

    Article  CAS  PubMed  Google Scholar 

  14. Tian J., Cai T., Yuan Z., Wang H., Liu L., Haas M., Maksimova E., Huang X.Y., Xie Z.J. 2006. Binding of Src to Na+/K+-ATPase forms a functional signaling complex. Mol. Biol. Cell. 17, 317–326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pasdois P., Quinlan C.L., Rissa A., Tariosse L., Vinassa B., Costa A.D., Pierre S.V., Dos Santos P., Garlid K.D. 2007. Ouabain protects rat hearts against ischemia–reperfusion injury via pathway involving src kinase, mitoKATP, and ROS. Am. J. Physiol. Heart Circ. Physiol. 292, H1470–1478.

    Article  CAS  PubMed  Google Scholar 

  16. Bogdanova A., Petrushanko I., Boldyrev A., Gassmann M. 2006. Oxygen-and redox-induced regulation of the Na/K-ATPase. Curr. Enzyme Inhibition. 2, 37–59.

    Article  CAS  Google Scholar 

  17. Petrushanko I.Y., Bogdanov N.B., Lapina N., Boldyrev A.A., Gassmann M., Bogdanova A.Y. 2007. Oxygen-induced regulation of Na/K-ATPase in cerebellar granule cells. J. Gen. Physiol. 130, 389–398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Petrushanko I., Bogdanov N., Bulygina E., Grenacher B., Leinsoo T., Boldyrev A., Gassmann M., Bogdanova A. 2006. Na-K-ATPase in rat cerebellar granule cells is redox sensitive. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R916–925.

    Article  CAS  PubMed  Google Scholar 

  19. Rasmussen H.H., Hamilton E.J., Liu C.C., Figtree G.A. 2010. Reversible oxidative modification: Implications for cardiovascular physiology and pathophysiology. Trends Cardiovasc. Med. 20, 85–90.

    Article  CAS  PubMed  Google Scholar 

  20. Petrushanko I.Y., Yakushev S., Mitkevich V.A., Kamanina Y.V., Ziganshin R.H., Meng X., Anashkina A.A., Makhro A., Lopina O.D., Gassmann M., Makarov A.A., Bogdanova A. 2012. S-glutathionylation of the Na, KATPase catalytic alpha subunit is a determinant of the enzyme redox sensitivity. J. Biol. Chem. 287, 32195–32205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Petrushanko I.Yu., Simonenko O.V., Burnysheva K.M., Klimanova E.A., Dergousova E.A., Mitkevich V.A., Lopina O.D., Makarov A.A. 2015. The ability of cells to adapt to low-oxygen conditions is associated with glutathionylation of Na, K-ATPase. Mol. Biol. (Moscow). 49 (1), 153–160.

    Article  CAS  Google Scholar 

  22. Smolyaninova L.V., Dergalev A.A., Kulebyakin K.Y., Carpenter D.O., Boldyrev A.A. 2013. Carnosine prevents necrotic and apoptotic death of rat thymocytes via ouabain-sensitive Na/K-ATPase. Cell. Biochem. Funct. 31, 30–35.

    Article  CAS  PubMed  Google Scholar 

  23. Kominato R., Fujimoto S., Mukai E., Nakamura Y., Nabe K., Shimodahira M., Nishi Y., Funakoshi S., Seino Y., Inagaki N. 2008. Src activation generates reactive oxygen species and impairs metabolism-secretion coupling in diabetic Goto-Kakizaki and ouabaintreated rat pancreatic islets. Diabetologia. 51, 1226–1235.

    Article  CAS  PubMed  Google Scholar 

  24. Hernansanz-Agustin P., Izquierdo-Alvarez A., Sanchez-Gomez F.J., Ramos E., Villa-Pina T., Lamas S., Bogdanova A., Martinez-Ruiz A. 2014. Acute hypoxia produces a superoxide burst in cells. Free Radic. Biol. Med. 71, 146–156.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology Russian Academy of Sciences, Moscow, 119991, Russia

    V. A. Lakunina, K. M. Burnysheva, V. A. Mitkevich, A. A. Makarov & I. Y. Petrushanko

Authors
  1. V. A. Lakunina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. M. Burnysheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. A. Mitkevich
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. A. Makarov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. Y. Petrushanko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Y. Petrushanko.

Additional information

Original Russian Text © V.A. Lakunina, K.M. Burnysheva, V.A. Mitkevich, A.A. Makarov, I.Y. Petrushanko, 2017, published in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 1, pp. 172–179.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lakunina, V.A., Burnysheva, K.M., Mitkevich, V.A. et al. Changes in the receptor function of Na,K-ATPase during hypoxia and ischemia. Mol Biol 51, 148–154 (2017). https://doi.org/10.1134/S0026893317010101

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893317010101

Keywords

Search

Navigation