Thromb Haemost 2007; 97(05): 795-802
DOI: 10.1160/TH06-08-0466
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Effect of staphylokinase-derived nonadecapeptide on the activation of plasminogen

Kiyotaka Okada
1   Department of Physiology
,
Shigeru Ueshima
1   Department of Physiology
2   Department of Food Science and Nutrition, Kinki University School of Agriculture, Nara, Japan
,
Hiroyuki Matsuno
3   Department of Clinical Pathological Biochemistry, Doshisha Women’s College of Liberal Arts, Kyoto, Japan
,
Naoyuki Kawao
1   Department of Physiology
,
Chikako Okamoto
1   Department of Physiology
,
Masaki Tanaka
4   Department of Surgery, Kinki University School of Medicine, Osakasayama, Japan
,
Osamu Matsuo
1   Department of Physiology
› Author Affiliations
Further Information

Publication History

Received 25 August 2006

Accepted after resubmission 02 March 2007

Publication Date:
24 November 2017 (online)

Summary

Staphylokinase (SAK) expresses plasminogen activator (PA) activity by forming a complex with plasmin. The interaction between the plasmin-SAK complex and plasminogen was investigated using synthesized peptides, which were constructed according to the amino acid sequence of the SAK molecule.A synthetic nonadecapeptide (SAK22–40) corresponding to Glu22-Leu40 by the SAK molecule enhanced the activation of Glu-plasminogen by the plasmin-SAK complex.Analysis of IAsys resonant mirror biosensor showed that SAK22–40 bound to Glu-plasminogen.This binding was completely inhibited by IgG against the B-chain in the plasminogen molecule. But, this binding was not inhibited by IgG against lysine-binding sites (LBS) of the A-chain in the plasminogen molecule. The substitution of Lys35 with Ala in SAK22–40 did not enhance the activation of Glu-plasminogen by the plasmin-SAK complex. When SAK22–40 was administrated in a mouse thrombosis model, earlier recanalization was observed than in mice with vehicle administration. Thus, a newly synthesized peptide, SAK22–40 enhanced Glu-plasminogen activation and induced effective thrombolysis.

 
  • References

  • 1 Lack CH. Staphylokinase: an activator of plasma protease. Nature 1948; 161: 559-560.
  • 2 Lijnen HR, Van Hoef B, De Cock F. et al. On the mechanism of fibrin-specific plasminogen activation by staphylokinase. J Biol Chem 1991; 266: 11826-11832.
  • 3 Sakai M, Watanuki M, Matsuo O. Mechanism of fibrin- specific fibrinolysis by staphylokinase: participation of α2-plasmin inhibitor. Biochem Biophys Res Commun 1989; 162: 830-837.
  • 4 Okada K, Ueshima S, Takaishi T. et al. Effects of fibrin and α2-antiplasmin on plasminogen activation by staphylokinase. Am J Hemat 1996; 53: 151-157.
  • 5 Matsuo O, Okada K, Fukao H. et al. Thrombolytic properties of staphylokinase. Blood 1990; 76: 925-929.
  • 6 Haijar KA. Cellular receptors in the regulation of plasmin generation. Thromb Haemost 1995; 74: 294-301.
  • 7 Molgaard L, Ponting CP, Christensen U. Glycosylation at Asn-289 facilitates the ligand-induced conformational changes of human Glu-plasminogen. FEBS Lett 1997; 405: 363-368.
  • 8 Petersen LC, Handest P, Brender J. et al. A sensitive solid-phase immunosorbent assay for tissue-type plasminogen activator activity in plasma using trinitrobenzoylated poly-D-lysine as a stimulator for plasminogen activation. Thromb Haemost 1987; 57: 205-211.
  • 9 Ohyama S, Harada T, Chikanishi T. et al. Nonlysine- analog plasmin(ogen) modulators promote autoproteolytic generation of plasminogen fragments with angiostatin-like activity. Eur J Biochem 2004; 271: 809-820.
  • 10 Rabijns A, De Bondt HL, De Ranter C. Three-dimensional structure of staphylokinase, a plasminogen activator with therapeutic potential. Nature Struct Biol 1997; 04: 357-360.
  • 11 Parry MAA, Fernandez-Catalan C, Bergner A. et al. The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor- substrate complex in action. Nature Struct Biol 1998; 05: 917-923.
  • 12 Jespers L, Van Herzeele N, Lijnen HR. et al. Arginine719 in human plasminogen mediator formation of the staphylokinase:plasmin activator complex. Biochemistry 1998; 37: 6380-6386.
  • 13 Jespers L, Vanwetswinkel S, Lijnen HR. et al. Structural and functional basis of plasminogen activation by staphylokinase. Thromb Haemost 1999; 81: 479-485.
  • 14 Sako T. Overproduction of staphylokinase in Escherichia coli and its characterization. Eur J Biochem 1985; 149: 557-563.
  • 15 Deutsch DG, Mertz ET. Plasminogen: purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096.
  • 16 Okada K, Nonaka T, Matsumoto H. et al. Effects of α2-plasmin inhibitor on plasminogen activation by staphylokinase/ plasminogen complex. Thromb Res 1994; 76: 211-220.
  • 17 Nieuwenhuizen W, Verheigen JH, Vermond A. et al. Plasminogen activation by tissue activator is accelerated in the presence of fibrin(ogen) cyanogens bromide fragment FCB-2. Biochem Biophys Acta 1983; 755: 531-533.
  • 18 Okada K, Ueshima S, Fukao H. et al. Analysis of complex formation between plasmin(ogen) and staphylokinase or streptokinase. Arch Biochem Biophys 2001; 393: 330-341.
  • 19 Okada K, Ueshima S, Tanaka M. et al. Analysis of plasminogen activation by the plasmin-staphylokinase complex in plasma of α2-antiplasmin-deficient mice. Blood Coagul Fibrin 2000; 11: 645-655.
  • 20 Ueshima S, Matsuno H, Hayashi M. et al. Function of tissue-type plasminogen activator releaser on vascular endothelial cells and thrombolysis in vivo. Thromb Haemost 2002; 87: 1069-1074.
  • 21 Mangel WF, Lin BH, Ramakrishnan V. Characterization of an extremely large, ligand-induced conformational change in plasminogen. Science 1990; 248: 69-73.
  • 22 An SS, Carreno C, Marti DN, Schaller J. et al. Lysine- 50 is a likely site for anchoring the plasminogen N-terminal peptide to lysine-binding kringles. Protein Sci 1998; 07: 1960-1969.
  • 23 Sun Z, Chen Y, Wang P. et al. The blockage of the high-affinity lysine binding sites of plasminogen by EACA significantly inhibits prourokinase-induced plasminogen activation. Biochim Biophy Acta 2002; 1596: 182-192.
  • 24 Yonekawa O, Vermond A, Nieuwenhuizen W. Localization in the fibrinogen gamma-chain of a new site that is involved in the acceleration of the tissue-type plasminogen activator-catalysed activation of plasminogen. Biochem J 1992; 283: 187-191.