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Kubala M, Čechová P, Geletičová J, et al. Flavonolignans As a Novel Class of Sodium Pump Inhibitors. Front Physiol. 2016;7:115doi: 10.3389/fphys.2016.00115.
Kubala, M., Čechová, P., Geletičová, J., Biler, M., Štenclová, T., Trouillas, P., & Biedermann, D. (2016). Flavonolignans As a Novel Class of Sodium Pump Inhibitors. Frontiers in physiology, 7115. https://doi.org/10.3389/fphys.2016.00115
Kubala, Martin, et al. "Flavonolignans As a Novel Class of Sodium Pump Inhibitors." Frontiers in physiology vol. 7 (2016): 115. doi: https://doi.org/10.3389/fphys.2016.00115
Kubala M, Čechová P, Geletičová J, Biler M, Štenclová T, Trouillas P, Biedermann D. Flavonolignans As a Novel Class of Sodium Pump Inhibitors. Front Physiol. 2016 Mar 30;7:115. doi: 10.3389/fphys.2016.00115. eCollection 2016. PMID: 27065883; PMCID: PMC4812144.
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Front Physiol. 2016 Mar 30;7:115. doi: 10.3389/fphys.2016.00115. eCollection 2016.

Flavonolignans As a Novel Class of Sodium Pump Inhibitors.

Frontiers in physiology

Martin Kubala, Petra Čechová, Jaroslava Geletičová, Michal Biler, Tereza Štenclová, Patrick Trouillas, David Biedermann

Affiliations

  1. Department of Biophysics, Faculty of Science, Centre of Region Haná for Biotechnological and Agricultural Research, Palacký University Olomouc, Czech Republic.
  2. Department of Biophysics, Faculty of Science, Centre of Region Haná for Biotechnological and Agricultural Research, Palacký UniversityOlomouc, Czech Republic; INSERM UMR 850, School of Pharmacy, University LimogesLimoges, France.
  3. INSERM UMR 850, School of Pharmacy, University LimogesLimoges, France; Department of Physical Chemistry, Faculty of Science, Regional Centre of Advanced Technologies and Materials, Palacký UniversityOlomouc, Czech Republic.
  4. Laboratory of Biotransformation, Institute of Microbiology, Czech Academy of Sciences Prague, Czech Republic.

PMID: 27065883 PMCID: PMC4812144 DOI: 10.3389/fphys.2016.00115

Abstract

We examined the inhibitory effects of three flavonolignans and their dehydro- derivatives, taxifolin and quercetin on the activity of the Na(+)/K(+)-ATPase (NKA). The flavonolignans silychristin, dehydrosilychristin and dehydrosilydianin inhibited NKA with IC50 of 110 ± 40 μM, 38 ± 8 μM, and 36 ± 14 μM, respectively. Using the methods of molecular modeling, we identified several possible binding sites for these species on NKA and proposed the possible mechanisms of inhibition. The binding to the extracellular- or cytoplasmic C-terminal sites can block the transport of cations through the plasma membrane, while the binding on the interface of cytoplasmic domains can inhibit the enzyme allosterically. Fluorescence spectroscopy experiments confirmed the interaction of these three species with the large cytoplasmic segment connecting transmembrane helices 4 and 5 (C45). The flavonolignans are distinct from the cardiac glycosides that are currently used in NKA treatment. Because their binding sites are different, the mechanism of inhibition is different as well as the range of active concentrations, one can expect that these new NKA inhibitors would exhibit also a different biomedical actions than cardiac glycosides.

Keywords: Na+/K+-ATPase; binding sites; flavonolignans; inhibition; sodium pump

References

  1. Science. 2013 Oct 4;342(6154):123-7 - PubMed
  2. J Phys Chem A. 2008 Feb 7;112(5):1054-63 - PubMed
  3. Kidney Int. 2002 Dec;62(6):2097-100 - PubMed
  4. Annu Rev Biochem. 2002;71:511-35 - PubMed
  5. Am J Physiol Cell Physiol. 2001 Oct;281(4):C1355-64 - PubMed
  6. J Comput Chem. 2009 Dec;30(16):2785-91 - PubMed
  7. Physiol Res. 2004;53(1):109-13 - PubMed
  8. Nat Prod Rep. 2014 Sep;31(9):1138-57 - PubMed
  9. Proteins. 2006 Jul 1;64(1):1-12 - PubMed
  10. Biochem Pharmacol. 2012 Jun 1;83(11):1507-13 - PubMed
  11. Eur Biophys J. 2003 Jul;32(4):363-9 - PubMed
  12. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014 Jun;158(2):194-200 - PubMed
  13. Biochim Biophys Acta. 2009 May;1788(5):1081-91 - PubMed
  14. Methods Enzymol. 1988;156:1-468 - PubMed
  15. World J Gastroenterol. 2011 May 14;17(18):2288-301 - PubMed
  16. Nature. 2007 Dec 13;450(7172):1043-9 - PubMed
  17. Annu Rev Physiol. 2003;65:817-49 - PubMed
  18. Biochemistry. 2003 Jun 3;42(21):6446-52 - PubMed
  19. Free Radic Biol Med. 2016 Jan;90:114-25 - PubMed
  20. J Comput Chem. 2010 Jan 30;31(2):455-61 - PubMed
  21. Bioorg Med Chem. 2006 Jun 1;14(11):3793-810 - PubMed
  22. Chem Biol Interact. 2013 Oct 5;205(3):173-80 - PubMed
  23. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13742-7 - PubMed
  24. J R Soc Promot Health. 2004 Jul;124(4):184-7 - PubMed
  25. Circulation. 2004 Jun 22;109(24):2959-64 - PubMed
  26. J Biol Chem. 2008 Oct 10;283(41):27982-90 - PubMed
  27. Anal Biochem. 1976 May 7;72:248-54 - PubMed
  28. J Biol Chem. 1996 Jun 14;271(24):14067-72 - PubMed
  29. Biochim Biophys Acta. 2013 Feb;1828(2):568-76 - PubMed
  30. Anticancer Res. 2006 Nov-Dec;26(6B):4457-98 - PubMed
  31. Mol Interv. 2008 Feb;8(1):36-49 - PubMed
  32. Biophys J. 2009 Sep 16;97(6):1756-64 - PubMed
  33. J Biol Chem. 2009 Jul 10;284(28):18715-25 - PubMed

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