Skip to main content

Advertisement

Log in

Effect of Nitric Oxide on the Functioning of the P-Glycoprotein Transporter

  • BIOPHYSICS AND BIOCHEMISTRY
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

We studied the effect of nitric oxide (NO) on the functioning of P-glycoprotein transporter (Pgp) in Caco-2 cells. NO donor S-nitrosoglutathione (GSNO) was used in concentrations of 1, 10, 50, 100, and 500 μM; the duration of exposure was 24 h. The content of Pgp was analyzed by the Western blotting, activity of the transport protein was analyzed by the transport of its substrate fexofenadine. It was shown that GSNO in concentrations of 10 and 50 μM increased the content and activity of Pgp. Increasing the GSNO concentration to 500 μM led to the development of nitrosative stress and a decrease in the content and activity of the transporter protein.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Dubinina EE, Gavrovskaya SV, Kuzmich EV, Leonova NV, Morozova MG, Kovrugina SV, Smirnova TA. Oxidative modification of proteins: oxidation of tryptophan and production of dityrosine in purified proteins using Fenton’s system. Biochemistry (Moscow). 2002;67(3):343-350. doi: 10.1023/A:1014840617890

  2. Kalinin RE, Shchulkin AV, Suchkov IA, Klimentova EA, Yakusheva EN, Egorov AA, Abalenikhina YuV, Chernykh IV. Vascular endothelial growth factor expression in arterial wall in various vascular diseases. Kardiol. Serd.-Sosud. Khir. 2020;13(6):556-560. doi: 10.17116/kardio202013061556.Russian.

  3. Metelskaya VA, Gumanova NG. Screening as a method for determining the serum level of nitric oxide metabolites. Klin. Lab. Diagnost. 2005;(6):15-18. Russian.

    Google Scholar 

  4. deBoer TR, Palomino RI, Mascharak PK. Peroxynitritemediated dimerization of 3-nitrotyrosine: unique chemistry along the spectrum of peroxynitrite-mediated nitration of tyrosine. Med. One. 2019;4:e190003. doi: 10.20900/mo.20190003

  5. Duan R, Hu N, Liu HY, Li J, Guo HF, Liu C, Liu L, Liu XD. Biphasic regulation of P-glycoprotein function and expression by NO donors in Caco-2 cells. Acta Pharmacol. Sin. 2012;33(6):767-774. doi: https://doi.org/10.1038/aps.2012.25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hemish J, Nakaya N, Mittal V, Enikolopov G. Nitric oxide activates diverse signaling pathways to regulate gene expression. J. Biol. Chem. 2003;278(43):42 321-42 329. doi: 10.1074/jbc.M308192200.

  7. Lobysheva II, Serezhenkov VA, Vanin AF. Interaction of peroxynitrite and hydrogen peroxide with dinitrosyl iron complexes containing thiol ligands in vitro. Biochemistry (Mosc). 1999;64(2):153-158.

    CAS  PubMed  Google Scholar 

  8. Lutzke A, Melvin AC, Neufeld MJ, Allison CL, Reynolds MM. Nitric oxide generation from S-nitrosoglutathione: new activity of indium and a survey of metal ion effects. Nitric Oxide. 2019;84:16-21. doi: https://doi.org/10.1016/j.niox.2019.01.005

    Article  CAS  PubMed  Google Scholar 

  9. Mollazadeh S, Sahebkar A, Hadizadeh F, Behravan J, Arabzadeh S. Structural and functional aspects of Pglycoprotein and its inhibitors. Life Sci. 2018;214:118-123. doi: https://doi.org/10.1016/j.lfs.2018.10.048

    Article  CAS  PubMed  Google Scholar 

  10. Murad F. Shattuck Lecture. Nitric oxide and cyclic GMP in cell signaling and drug development. N. Engl. J. Med. 2006;355(19):2003-2011. doi: https://doi.org/10.1056/NEJMsa063904

    Article  CAS  Google Scholar 

  11. Nawa A, Fujita-Hamabe W, Nakamoto K, Tokuyama S. Nitric oxide synthase-mediated alteration of intestinal P-glycoprotein under hyperglycemic stress. Yakugaku Zasshi. 2011;131(4):487-492. doi: 10.1248/yakushi.131.487

  12. Ramachandran N, Root P, Jiang XM, Hogg PJ, Mutus B. Mechanism of transfer of NO from extracellular S-nitrosothiols into the cytosol by cell-surface protein disulfide isomerase. Proc. Natl Acad. Sci. USA. 2001;98(17):9539-9544. doi: https://doi.org/10.1073/pnas.171180998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Robertson SJ, Mokgokong R, Kania KD, Guedj AS, Hladky SB, Barrand MA. Nitric oxide contributes to hypoxia-reoxygenation-induced P-glycoprotein expression in rat brain endothelial cells. Cell. Mol. Neurobiol. 2011;31(7):1103-1111. doi: https://doi.org/10.1007/s10571-011-9711-4

    Article  CAS  PubMed  Google Scholar 

  14. Shchulkin AV, Abalenikhina YV, Erokhina PD, Chernykh IV, Yakusheva EN. The role of P-glycoprotein in decreasing cell membranes permeability during oxidative stress. Biochemistry (Mosc). 2021;86(2):197-206. doi: https://doi.org/10.1134/S0006297921020085

    Article  CAS  PubMed  Google Scholar 

  15. Socco S, Bovee RC, Palczewski MB, Hickok JR, Thomas DD. Epigenetics: The third pillar of nitric oxide signaling. Pharmacol. Res. 2017;121:52-58. doi: 10.1016/j.phrs.2017.04.011

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yu. V. Abalenikhina.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 173, No. 1, pp. 38-42, January, 2022

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abalenikhina, Y.V., Sudakova, E.A., Slepnev, A.A. et al. Effect of Nitric Oxide on the Functioning of the P-Glycoprotein Transporter. Bull Exp Biol Med 173, 28–32 (2022). https://doi.org/10.1007/s10517-022-05486-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-022-05486-3

Key Words

Navigation