Purification and Characterization of a New RGD/KGD-Containing Dimeric Disintegrin, Piscivostatin, from the Venom of Agkistrodon piscivorus piscivorus : The Unique Effect of Piscivostatin on Platelet Aggregation

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Author(s)

Abstract

Piscivostatin, a novel dimeric disintegrin containing Arg-Gly-Asp (RGD) and Lys-Gly-Asp (KGD) sequences, was isolated from the venom of <i>Agkistrodon piscivorus piscivorus.</i> The molecule consisted of two chains designated as the α and β chains, comprising 65 and 68 amino acid residues, respectively. Piscivostatin had two binding motifs recog-nized by platelet glycoprotein IIb/IIIa (GPIIb/IIIa), and the biological activity of dimeric disintegrin piscivostatin toward platelet aggregation differed from those of other mono-meric disintegrins such as trimestatin and echistatin. We measured platelet aggregation by the laser light scattering method during the process of ADP-induced platelet aggre-gation. Both dimeric and monomeric disintegrins inhibited the formation of small (9 to 25 _??_m in diameter), medium-sized and large aggregates (25 to 70 _??_m in diameter) in a dose-dependent manner. The platelet aggregates disaggregated after reaching a maxi-mal number on either treatment with ADP alone or monomeric disintegrin/ADP. How-ever, the small aggregates did not disaggregate on treatment with piscivostatin/ADP even when applied over time. When washed platelets were incubated with an anti-GPIIb/IIIa monoclonal antibody, PT25-2, which induces conformational changes of GPIIb/IIIa to a form accessible to fibrinogen and other adhesion proteins without plate-let activation, piscivostatin induced a platelet shape change alone with no aggregate formation. The present study indicated that piscivostatin has two unique contradictory activities; acting as a double inhibitor of platelet aggregation and platelet aggregate dis-sociation.

Journal

  • The Journal of Biochemistry

    The Journal of Biochemistry 130(3), 407-415, 2001-09-01

    The Japanese Biochemical Society

References:  36

Codes

  • NII Article ID (NAID)
    10007858582
  • NII NACSIS-CAT ID (NCID)
    AA00694073
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    0021924X
  • NDL Article ID
    5898341
  • NDL Source Classification
    ZR2(科学技術--生物学--生化学)
  • NDL Call No.
    Z53-B472
  • Data Source
    CJP  NDL  J-STAGE 
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