Effect of staphylokinase-derived nonadecapeptide on the activation of plasminogen

Kiyotaka Okada; Shigeru Ueshima; Hiroyuki Matsuno; Naoyuki Kawao; Chikako Okamoto; Masaki Tanaka; Osamu Matsuo

doi:10.1160/TH06-08-0466

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Physiology

,

Shigeru Ueshima

¹Department of Physiology

²Department of Food Science and Nutrition, Kinki University School of Agriculture, Nara, Japan

,

Hiroyuki Matsuno

³Department of Clinical Pathological Biochemistry, Doshisha Women’s College of Liberal Arts, Kyoto, Japan

,

Naoyuki Kawao

¹Department of Physiology

,

Chikako Okamoto

¹Department of Physiology

,

Masaki Tanaka

⁴Department of Surgery, Kinki University School of Medicine, Osakasayama, Japan

,

Osamu Matsuo

¹Department of Physiology

› Author Affiliations

Abstract

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.

Keywords

Staphylokinase - plasminogen - synthetic peptide - plasminogen activation - thrombolysis

Full Text

References

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