Skip to main content
SpringerLink
Log in

The effect of myeloperoxidase isoforms on biophysical properties of red blood cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Myeloperoxidase (MPO), an oxidant-producing enzyme, stored in azurophilic granules of neutrophils has been recently shown to influence red blood cell (RBC) deformability leading to abnormalities in blood microcirculation. Native MPO is a homodimer, consisting of two identical protomers (monomeric MPO) connected by a single disulfide bond but in inflammatory foci as a result of disulfide cleavage monomeric MPO (hemi-MPO) can also be produced. This study investigated if two MPO isoforms have distinct effects on biophysical properties of RBCs. We have found that hemi-MPO, as well as the dimeric form, bind to the glycophorins A/B and band 3 protein on RBC’s plasma membrane, that lead to reduced cell resistance to osmotic and acidic hemolysis, reduction in cell elasticity, significant changes in cell volume, morphology, and the conductance of RBC plasma membrane ion channels. Furthermore, we have shown for the first time that both dimeric and hemi-MPO lead to phosphatidylserine (PS) exposure on the outer leaflet of RBC membrane. However, the effects of hemi-MPO on the structural and functional properties of RBCs were lower compared to those of dimeric MPO. These findings suggest that the ability of MPO protein to influence RBC’s biophysical properties depends on its conformation (dimeric or monomeric isoform). It is intriguing to speculate that hemi-MPO appearance in blood during inflammation can serve as a regulatory mechanism addressed to reduce abnormalities on RBC response, induced by dimeric MPO.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Furtmüller PG, Burner U, Obinger C (1998) Reaction of myeloperoxidase compound I with chloride, bromide, iodide, and thiocyanate. Biochemistry 37(51):17923–17930. https://doi.org/10.1021/bi9818772

    Article  PubMed  Google Scholar 

  2. Davies MJ, Hawkins CL, Pattison DI, Rees MD (2008) Mammalian heme peroxidases: from molecular mechanisms to health implications. Antioxid Redox Signal 10(7):1199–1234. https://doi.org/10.1089/ars.2007.1927

    Article  CAS  PubMed  Google Scholar 

  3. Morgan PE, Pattison DI, Talib J, Summers FA, Harmer JA, Celermajer DS, Hawkins CL, Davies MJ (2011) High plasma thiocyanate levels in smokers are a key determinant of thiol oxidation induced by myeloperoxidase. Free Radic Biol Med 51(9):1815–1822. https://doi.org/10.1016/j.freeradbiomed.2011.08.008

    Article  CAS  PubMed  Google Scholar 

  4. Chandler JD, Day BJ (2015) Biochemical mechanisms and therapeutic potential of pseudohalide thiocyanate in human health. Free Radic Res 49(6):695–710. https://doi.org/10.3109/10715762.2014.1003372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pattison DI, Davies MJ (2006) Reactions of myeloperoxidase-derived oxidants with biological substrates: gaining chemical insight into human inflammatory diseases. Curr Med Chem 13(27):3271–3290. https://doi.org/10.2174/092986706778773095

    Article  CAS  PubMed  Google Scholar 

  6. Panasenko OM, Gorudko IV, Sokolov AV (2013) Hypochlorous acid as a precursor of free radicals in living systems. Biochemistry (Moscow) 78(13):1466–1489. https://doi.org/10.1134/S0006297913130075

    Article  CAS  Google Scholar 

  7. Panasenko OM, Sergienko VI (2010) Halogenizing stress and its biomarkers [Article in Russian]. Vestn Ross Akad Med Nauk 1:27–39

    Google Scholar 

  8. Yap YW, Whiteman M, Cheung NS (2007) Chlorinative stress: an under appreciated mediator of neurodegeneration? Cell Signal 19(2):219–228. https://doi.org/10.1016/j.cellsig.2006.06.013

    Article  CAS  PubMed  Google Scholar 

  9. Gorudko IV, Sokolov AV, Shamova EV, Grudinina NA, Drozd ES, Shishlo LM, Grigorieva DV, Bushuk SB, Bushuk BA, Chizhik SA, Cherenkevich SN, Vasilyev VB, Panasenko OM (2013) Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry. Biol Open 2(9):916–923. https://doi.org/10.1242/bio.20135314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kolarova H, Klinke A, Kremserova S, Adam M, Pekarova M, Baldus S, Eiserich JP, Kubala L (2013) Myeloperoxidase induces the priming of platelets. Free Radic Biol Med 61:357–369. https://doi.org/10.1016/j.freeradbiomed.2013.04.014

    Article  CAS  PubMed  Google Scholar 

  11. Klinke A, Nussbaum C, Kubala L, Friedrichs K, Rudolph TK, Rudolph V, Paust HJ, Schröder C, Benten D, Lau D, Szocs K, Furtmüller PG, Heeringa P, Sydow K, Duchstein HJ, Ehmke H, Schumacher U, Meinertz T, Sperandio M, Baldus S (2011) Myeloperoxidase attracts neutrophils by physical forces. Blood 117(4):1350–1358. https://doi.org/10.1182/blood-2010-05-284513

    Article  CAS  PubMed  Google Scholar 

  12. Lau D, Mollnau H, Eiserich JP, Freeman BA, Daiber A, Gehling UM, Brümmer J, Rudolph V, Münzel T, Heitzer T, Meinertz T, Baldus S (2005) Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Proc Natl Acad Sci USA 102(2):431–436. https://doi.org/10.1073/pnas.0405193102

    Article  CAS  PubMed  Google Scholar 

  13. Gorudko IV, Sokolov AV, Shamova EV, Grigorieva DV, Mironova EV, Kudryavtsev IV, Gusev SA, Gusev AA, Chekanov AV, Vasilyev VB, Cherenkevich SN, Panasenko OM, Timoshenko AV (2016) Binding of human myeloperoxidase to red blood cells: molecular targets and biophysical consequences at the plasma membrane level. Arch Biochem Biophys 591:87–97. https://doi.org/10.1016/j.abb.2015.12.007

    Article  CAS  PubMed  Google Scholar 

  14. Benson TW, Weintraub NL, Kim HW, Seigler N, Kumar S, Pye J, Horimatsu T, Pellenberg R, Stepp DW, Lucas R, Bogdanov VY, Litwin SE, Brittain JE, Harris RA (2018) A single high-fat meal provokes pathological erythrocyte remodeling and increases myeloperoxidase levels: implications for acute coronary syndrome. Lab Invest 98(10):1300–1310. https://doi.org/10.1038/s41374-018-0038-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Blair-Johnson M, Fiedler T, Fenna R (2001) Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 Å resolution. Biochemistry 40(46):13990–13997. https://doi.org/10.1021/bi0111808

    Article  CAS  PubMed  Google Scholar 

  16. Yamada M, Mori M, Sugimura T (1981) Myeloperoxidase in cultured human promyelocytic leukemia cell line HL-60. Biochem Biophys Res Commun 98(1):219–226. https://doi.org/10.1016/0006-291X(81)91891-X

    Article  CAS  PubMed  Google Scholar 

  17. Yamada M, Mori M, Sugimura T (1983) Myeloperoxidase of human myeloid leukemia cells HL-60 drown in culture and in nude mice. J Biochem 93(6):1661–1668

    Article  CAS  Google Scholar 

  18. Andrews PC, Krinsky NI (1981) The reductive cleavage of myeloperoxidase in half, producing enzymically active hemi-myeloperoxidase. J Biol Chem 256(9):4211–4218

    CAS  PubMed  Google Scholar 

  19. Gorudko IV, Mikhalchik EV, Sokolov AV, Grigorieva DV, Kostevich VA, Vasilyev VB, Cherenkevich SN, Panasenko OM (2017) The production of reactive oxygen and halogen species by neutrophils in response to monomeric forms of myeloperoxidase. Biophysics 62(6):919–925. https://doi.org/10.1134/S0006350917060069

    Article  CAS  Google Scholar 

  20. Gorudko IV, Grigorieva DV, Sokolov AV, Shamova EV, Kostevich VA, Kudryavtsev IV, Syromiatnikova ED, Vasilyev VB, Cherenkevich SN, Panasenko OM (2018) Neutrophil activation in response to monomeric myeloperoxidase. Biochem Cell Biol 96(5):592–601. https://doi.org/10.1139/bcb-2017-0290

    Article  CAS  PubMed  Google Scholar 

  21. Zuurbier KW, van den Berg JD, Van Gelder BF, Muijsers AO (1992) Human hemi-myeloperoxidase. Initial chlorinating activity at neutral pH, compound II and III formation, and stability towards hypochlorous acid and high temperature. Eur J Biochem 205(2):737–742. https://doi.org/10.1111/j.1432-1033.1992.tb16837.x

    Article  CAS  PubMed  Google Scholar 

  22. Sokolov AV, Kostevich VA, Gorbunov NP, Grigorieva DV, Gorudko IV, Vasilyev VB, Panasenko OM (2018) A link between active myeloperoxidase and chlorinated ceruloplasmin in blood plasma of patients with cardiovascular diseases. Med Immunol 20(5):699–710. https://doi.org/10.15789/1563-0625-2018-5-699-710(Russian)

    Article  Google Scholar 

  23. Hope HR, Remsen EE, Lewis C Jr, Heuvelman DM, Walker MC, Jennings M, Connolly DT (2000) Large-scale purification of myeloperoxidase from HL60 promyelocytic cells: characterization and comparison to human neutrophil myeloperoxidase. Protein Expr Purif 18(3):269–276. https://doi.org/10.1006/prep.1999.1197

    Article  CAS  PubMed  Google Scholar 

  24. Sokolov AV, Kostevich VA, Zakharova ET, Samygina VR, Panasenko OM, Vasilyev VB (2015) Interaction of ceruloplasmin with eosinophil peroxidase as compared to its interplay with myeloperoxidase: reciprocal effect on enzymatic properties. Free Radic Re 49(6):800–811. https://doi.org/10.3109/10715762.2015.1005615

    Article  CAS  Google Scholar 

  25. Vakhrusheva TV, Sokolov AV, Kostevich VA, Vasilyev VB, Panasenko OM (2018) Enzymatic and bactericidal activity of monomeric and dimeric forms of myeloperoxidase. Biochem Moscow Suppl Ser B 12(3):258–265. https://doi.org/10.1134/S1990750818030083

    Article  Google Scholar 

  26. Fling SP, Gregerson DS (1986) Peptide and protein molecular weight determination by electrophoresis using a high-molarity tris buffer system without urea. Anal Biochem 155(1):83–88. https://doi.org/10.1016/0003-2697(86)90228-9

    Article  CAS  PubMed  Google Scholar 

  27. Anderson NL, Nance SL, Pearson TW, Anderson NG (1982) Two-dimensional electrophoretic patterns of human plasma membrane proteins immobilized on nitrocellulose. Electrophoresis 3:135–142

    Article  CAS  Google Scholar 

  28. Sokolov AV, Pulina MO, Ageeva KV, Tcherkalina OS, Zakharova ET, Vasilyev VB (2009) Identification of complexes formed by ceruloplasmin with matrix metalloproteinases 2 and 12. Biochemistry (Mosc) 74(12):1388–1392. https://doi.org/10.1134/S0006297909120141

    Article  CAS  Google Scholar 

  29. Drozd ES, Chizhik SA (2008) Combined atomic force microscopy and optical microscopy measurements as a method of erythrocyte investigation. Proc SPIE. https://doi.org/10.1117/12.836481

    Article  Google Scholar 

  30. Mathur AB, Collinsworth AM, Reichert WM, Kraus WE, Truskey GA (2001) Endothelial, cardiac muscle and skeletal muscle exhibit different viscous and elastic properties as determined by atomic force microscopy. J Biomech 34(12):1545–1553. https://doi.org/10.1016/S0021-9290(01)00149-X

    Article  CAS  PubMed  Google Scholar 

  31. Adam M, Gajdova S, Kolarova H, Kubala L, Lau D, Geisler A, Ravekes T, Rudolph V, Tsao PS, Blankenberg S, Baldus S, Klinke A (2014) Red blood cells serve as intravascular carriers of myeloperoxidase. J Mol Cell Cardiol 74:353–363. https://doi.org/10.1016/j.yjmcc.2014.06.009

    Article  CAS  PubMed  Google Scholar 

  32. Gorudko IV, Cherkalina OS, Sokolov AV, Pulina MO, Zakharova ET, Vasilyev VB, Cherenkevich SN, Panasenko OM (2009) New approaches to the measurement of the concentration and peroxidase activity of myeloperoxidase in human blood plasma. Bioorgan Khim 35:629–639

    CAS  Google Scholar 

  33. Zavodnik LB, Zavodnik IB, Lapshyna EA, Buko VU, Bryszewska MJ (2002) Hypochlorous acid-induced membrane pore formation in red blood cells. Bioelectrochemistry 58(2):157–161. https://doi.org/10.1016/S1567-5394(02)00151-2

    Article  CAS  PubMed  Google Scholar 

  34. Zavodnik LB, Zavodnik IB, Lapshina EA, Shkodich AP, Bryszewska M, Buko VU (2000) Hypochlorous acid-induced lysis of human erythrocytes. Inhibition of cellular damage by the isoflavonoid genistein-8-C-glucoside. Biochemistry (Mosc) 65(8):946–951

    CAS  Google Scholar 

  35. Bevers EM, Williamson PL (2010) Phospholipid scramblase: an update. FEBS Lett 584(13):2724–2730. https://doi.org/10.1016/j.febslet.2010.03.020

    Article  CAS  PubMed  Google Scholar 

  36. Wesseling MC, Wagner-Britz L, Huppert H, Hanf B, Hertz L, Nguyen DB, Bernhardt I (2016) Phosphatidylserine exposure in human red blood cells depending on cell age. Cell Physiol Biochem 38(4):1376–1390. https://doi.org/10.1159/000443081

    Article  CAS  PubMed  Google Scholar 

  37. Jacobi J, Lang E, Bissinger R, Frauenfeld L, Modicano P, Faggio C, Abed M, Lang F (2014) Stimulation of erythrocyte cell membrane scrambling by mitotane. Cell Physiol Biochem 33(5):1516–1526. https://doi.org/10.1159/000358715

    Article  CAS  PubMed  Google Scholar 

  38. Nguyen DB, Wagner-Britz L, Maia S, Steffen P, Wagner C, Kaestner L, Bernhardt I (2011) Regulation of phosphatidylserine exposure in red blood cells. Cell Physiol Biochem 28(5):847–856. https://doi.org/10.1159/000335798

    Article  CAS  PubMed  Google Scholar 

  39. Kebir D, József L, Pan W, Filep JG (2008) Myeloperoxidase delays neutrophil apoptosis through CD11b/CD18 integrins and prolongs inflammation. Circ Res 103(4):352–359. https://doi.org/10.1161/01.RES.0000326772.76822.7a

    Article  CAS  PubMed  Google Scholar 

  40. Johansson MW, Patarroyo M, Oberg F, Siegbahn A, Nilsson K (1997) Myeloperoxidase mediates cell adhesion via the alpha M beta 2 integrin (Mac-1, CD11b/CD18). J Cell Sci 110(Pt9):1133–1139

    CAS  PubMed  Google Scholar 

  41. Closse C, Dachary-Prigent J, Boisseau MR (1999) Phosphatidylserine-related adhesion of human erythrocytes to vascular endothelium. Br J Haematol 107:300–302. https://doi.org/10.1046/j.1365-2141.199.01718.x

    Article  CAS  PubMed  Google Scholar 

  42. Grochmal A, Ferrero E, Milanesi L, Tomas S (2013) Modulation of in-membrane receptor clustering upon binding of multivalent ligands. J Am Chem Soc 135(27):10172–10177. https://doi.org/10.1021/ja404428u

    Article  CAS  PubMed  Google Scholar 

  43. Jung H, Robison AD, Cremer PS (2009) Multivalent ligand-receptor binding on supported lipid bilayers. J Struct Biol 168(1):90–94. https://doi.org/10.1016/j.jsb.2009.05.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Nigg EA, Bron C, Girardet M, Cherry RJ (1980) Band 3-glycophorin A association in erythrocyte membrane demonstrated by combining protein diffusion measurements with antibody-induced cross-linking. Biochemistry 19(9):1887–1893. https://doi.org/10.1021/bi00550a024

    Article  CAS  PubMed  Google Scholar 

  45. Auffray I, Marfatia S, de Jong K, Lee G, Huang CH, Paszty C, Tanner MJ, Mohandas N, Chasis JA (2001) Glycophorin A dimerization and band 3 interaction during erythroid membrane biogenesis: in vivo studies in human glycophorin A transgenic mice. Blood 97(9):2872–2878. https://doi.org/10.1182/blood.V97.9.2872

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was partly supported by Russian Foundation for Basic Research (Grant 18-515-00004, Grant 17-54-04009), Belarusian Republican Foundation for Fundamental Research (Grant B18R-058) and Russian President’s grant MD-5133.2018.4.

Author information

Authors and Affiliations

  1. Belarusian State University, Minsk, Belarus

    Ekaterina V. Shamova, Irina V. Gorudko, Daria V. Grigorieva, Anatoli U. Kokhan & Sergey N. Cherenkevich

  2. FSBSI “Institute of Experimental Medicine”, St. Petersburg, Russia

    Alexey V. Sokolov & Vadim B. Vasilyev

  3. Saint-Petersburg State University, St. Petersburg, Russia

    Alexey V. Sokolov & Vadim B. Vasilyev

  4. Federal Research and Clinical Center of Physical–Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia

    Alexey V. Sokolov, Sergey A. Gusev & Oleg M. Panasenko

  5. A.V. Luikov Heat and Mass Transfer Institute of the National Academy of Sciences of Belarus, Minsk, Belarus

    Galina B. Melnikova

  6. State Institution “N.N. Alexandrov Republican Scientific and Practical Center of Oncology and Medical Radiology”, Minsk, Belarus

    Nikolai A. Yafremau

  7. Lomonosov Moscow State University, Moscow, Russia

    Anastasia N. Sveshnikova

  8. Pirogov Russian National Research Medical University, Moscow, Russia

    Oleg M. Panasenko

Authors
  1. Ekaterina V. Shamova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irina V. Gorudko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daria V. Grigorieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexey V. Sokolov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anatoli U. Kokhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Galina B. Melnikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nikolai A. Yafremau
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sergey A. Gusev
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Anastasia N. Sveshnikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vadim B. Vasilyev
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sergey N. Cherenkevich
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Oleg M. Panasenko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ekaterina V. Shamova.

Ethics declarations

Conflict of interest

The authors declare no competing financial and nonfinancial interests.

Ethical approval

This work was approved by the protocol of the Local Ethics Committee at Federal State Budgetary Scientific Institution “Institute of Experimental Medicine”.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 83 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shamova, E.V., Gorudko, I.V., Grigorieva, D.V. et al. The effect of myeloperoxidase isoforms on biophysical properties of red blood cells. Mol Cell Biochem 464, 119–130 (2020). https://doi.org/10.1007/s11010-019-03654-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-019-03654-0

Keywords

Search

Navigation