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Effect of Specific Cleavage of Immunoglobulin G by Plasmin on the Binding and Activation of Plasminogen

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Abstract

A method of ELISA for measuring the binding of different samples of immunoglobulin (IgG) and its fragments to human plasminogen (Pg) has been developed. Instead of plasminogen, the heavy chain of plasminogen (Pg-H) containing five ligand-binding kringle domains, immobilized on the surface of the plate, was used in this method as a detector. It was found that IgG treated with plasmin (IgGPm-t) binds to the immobilized Pg-H 2.84 times more strongly than intact IgG. Both IgG samples showed a weak nonspecific binding to the immobilized light chain of plasminogen (Pg-L). It was shown that 0.2 M L-lysine inhibits the binding of IgGPm-t and does not affect the nonspecific binding of intact IgG to the immobilized Pg-H, indicating the involvement of lysine-binding regions of Pg-H in binding to IgGPm-t. A preliminary treatment of IgG samples with carboxypeptidase В (CPB) inhibited the binding of IgGPm-t and did not affect the nonspecific binding of intact IgG to the immobilized Pg-H, which indicates a key role of the С-terminal lysine of IgGPm-t in the specific binding to the lysine-binding sites of Pg. The study of the effects of intact IgG and IgGPm-t on the rate of activation of Glu- and Lys-forms of Pg (Glu-Pg and Lys-Pg) by a tissue activator of Pg (tPA) and urokinase (uPA) in buffer showed that intact IgG completely inhibited the activation of Glu-Pg and Lys-Pg with both tPA and uPA. Presumably, the inhibitory effect of intact IgG is due to steric hindrances that it creates for protein–protein interactions of the activators with the zymogen. IgGPm-t accelerated the generation of plasmin from Pg. In this case, the stimulatory effect of IgGPm-t on the activation of Glu-Pg under the action of tPA was ∼25% higher than on the activation of Lys-Pg, which is explained by more significant conformational changes in the Glu-Pg molecule compared with the Lys-Pg molecule after their binding to IgGPm-t. The results suggest that the specific cleavage of IgG by plasmin may be one of the ways by which the plasminogen/plasmin system is involved in various physiological and pathological processes.

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Abbreviations

Alb:

human albumin

AlbPm-t :

human albumin treated with plasmin

6-AHA:

6-aminohexanoic acid

uPA:

two-chain urokinase

IgG:

immunoglobulin G

IgGPm-t :

IgG treated with plasmin

CPB:

carboxypeptidase В

K:

kringle domain

LBS:

lysine-binding site

Pm:

plasmin

Pg:

plasminogen

Glu-Pg and Lys-Pg:

Glu- and Lys-forms of plasminogen

NTP:

N-terminal peptide

tPA:

tissue activator of plasminogen

Pg-H and Pg-L:

the heavy and light chains of plasmin(ogen)

References

  1. Ponting, C.P., Marshall, J.M., and Cederholm-Williams, S.A., Blood Coagul. Fibrinolysis, 1992, vol. 3, pp. 605–614.

    Article  CAS  PubMed  Google Scholar 

  2. Aisina, R.B. and Mukhametova, L.I., Russ. J. Bioorg. Chem., 2014, vol. 40, pp. 590–605.

    Article  CAS  Google Scholar 

  3. Thorsen, S., Clemmensen, I., Sottrup Jensen, L., and Magnusson, S., Biochim. Biophys. Acta, 1981, vol. 668, pp. 377–387.

    Article  CAS  PubMed  Google Scholar 

  4. Miles, L.A. and Parmer, R.J., Semin. Thromb. Hemost., 2013, vol. 39, pp. 329–337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rijken, D.C. and Sakharov, D.V., Thromb. Res., 2001, vol. 103, pp. 41–49.

    Article  Google Scholar 

  6. Castellino, F.J. and Ploplis, V.A., Thromb. Haemost., 2005, vol. 93, pp. 647–654.

    CAS  PubMed  Google Scholar 

  7. Ogiwara, K., Nogami, K., Nishiya, K., and Shima, M., Blood Coagul. Fibrinolysis, 2010, vol. 21, pp. 568–576.

    Article  CAS  PubMed  Google Scholar 

  8. Pryzdial, E.L., Lavigne, N., Dupuis, N., and Kessler, G.E., J. Biol. Chem., 1999, vol. 274, pp. 8500–8505.

    Article  CAS  PubMed  Google Scholar 

  9. Waisman, D.M., Plasminogen: Structure, Activation and Regulation, Waisman, D.M., Ed., New York: Springer, Kluwer Academic/Plenum Publishers, 2003.

  10. Santala, A., Saarinen, J., Kovanen, P., and Kuusela, P., FEBS Lett., 1999, vol. 461, pp. 153–156.

    Article  CAS  PubMed  Google Scholar 

  11. Law, R.H.P., Abu-Ssaydeh, D., and Whisstock, C., Curr. Opin. Struct. Biol., 2013, vol. 23, pp. 836–841.

    Article  CAS  PubMed  Google Scholar 

  12. Wiman, B. and Collen, D., Nature, 1978, vol. 272, pp. 549–550.

    Article  CAS  PubMed  Google Scholar 

  13. Radcliffe, R. and Heinze, T., Arch. Biochem. Biophys., 1981, vol. 211, pp. 750–761.

    Article  CAS  PubMed  Google Scholar 

  14. Machovich, R. and Owen, W., Arch. Biochem. Biophys., 1977, vol. 344, pp. 343–349.

    Article  Google Scholar 

  15. Harpel, P.C., Sullivan, R., and Chang, T.-S., J. Biol. Chem., 1989, vol. 264, pp. 616–624.

    CAS  PubMed  Google Scholar 

  16. Dano, K., Behrendt, N., Hoyer-Hansen, G., Johnsen, M., Lund, L.R., Ploug, M., and Romer, J., Thromb. Haemost., 2005, vol. 93, pp. 676–681.

    CAS  PubMed  Google Scholar 

  17. Brezski, R.J. and Jordan, R.E., BioScience, 2010, vol. 2, pp. 212–220.

    Google Scholar 

  18. Gonzalez-Gronow, M., Cuchacovich, M., Grigg, D.M., and Pizzo, S.V., J. Mol. Med., 1996, vol. 74, pp. 463–469.

    Article  CAS  PubMed  Google Scholar 

  19. Stefanescu, M., Szegli, G., Cremer, L., Zarma, L., Mazilu, E., Naghiu, M., Niculescu, D., Gaches, A., and Onu, A., Arch. Roum. Pathol. Exp. Microbiol., 1989, vol. 48, pp. 47–53.

    CAS  PubMed  Google Scholar 

  20. Kozmin, Ya.D., Bliznyukov, O.P., Martynov, A.I., and Alekberova, Z.S., Immunologiya, 2004, vol. 25, pp. 56–62.

    Google Scholar 

  21. Goufman, E.I., Yakovlev, V.N., Tikhonova, N.B., Aisina, R.B., Yarygin, K.N., Mukhametova, L.I., Gershkovich, K.B., and Gulin, D.A., Bull. Experim. Biol. Med., 2015, vol. 158, pp. 493–496.

    Article  CAS  Google Scholar 

  22. Law, R.H., Caradoc-Davies, T., Cowieson, N., Horvath, A.J., Quek, A.J., et al., Cell Rep., 2012, vol. 1, pp. 185–190.

    Article  CAS  PubMed  Google Scholar 

  23. Levashov, M.Yu., Aisina, R.B., Gershkovich, K.B., and Varfolomeyev, S.D., Biochemistry (Moscow), 2007, vol. 72, pp. 707–715.

    Article  CAS  Google Scholar 

  24. Laemmly, U.K., Nature, 1970, vol. 227, pp. 680–685.

    Article  Google Scholar 

  25. Aisina, R.B., Mukhametova, L.I., Gulin, D.A., Levashov, M.Y., Prisyazhnaya, N.V., Gershkovich, K.B., and Varfolomeyev, S.D., Biochemistry (Moscow), 2009, vol. 74, pp. 1104–1113.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Chemical Faculty, Moscow State University, Moscow, 119992, Russia

    R. B. Aisina & L. I. Mukhametova

  2. Bauman State Technical University, Moscow, Russia

    L. I. Mukhametova

  3. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119991, Russia

    K. B. Gershkovich

  4. OOO Angiogen, Moscow, 101000, Russia

    V. N. Yakovlev

  5. Research Institute of Human Morphology, Moscow, 117418, Russia

    E. I. Goufman & N. B. Tikhonova

Authors
  1. R. B. Aisina
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  2. L. I. Mukhametova
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  3. K. B. Gershkovich
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  4. V. N. Yakovlev
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  5. E. I. Goufman
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  6. N. B. Tikhonova
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Correspondence to R. B. Aisina.

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Original Russian Text © R.B. Aisina, L.I. Mukhametova, K.B. Gershkovich, V.N. Yakovlev, E.I. Goufman, N.B. Tikhonova, 2018, published in Bioorganicheskaya Khimiya, 2018, Vol. 44, No. 2, pp. 194–202.

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Aisina, R.B., Mukhametova, L.I., Gershkovich, K.B. et al. Effect of Specific Cleavage of Immunoglobulin G by Plasmin on the Binding and Activation of Plasminogen. Russ J Bioorg Chem 44, 210–216 (2018). https://doi.org/10.1134/S1068162018010028

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  • DOI: https://doi.org/10.1134/S1068162018010028

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