Interaction of a plasminogen activator proteinase, LV-PA with human α2-macroglobulin

Ana L. Hermogenes, Michael Richardson, Arinos Magalhaes, Armando Yarleque, Edith Rodriguez, Eladio F. Sanchez

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Lachesis venom plasminogen activator (LV-PA) is a 33-kDa serine proteinase isolated from bushmaster (Lachesis muta muta) snake venom, which activates the fibrinolytic system in vitro. This study has examined the effect of the plasma proteinase inhibitor α2-macroglobulin (α2-M) towards LV-PA and compares it with the effect on tissue type plasminogen activator (t-PA). The proteolytic activity of LV-PA alone or previously incubated with human plasminogen (Plg) on the large molecular mass protein substrates, dimethylcasein (DMC) and fibrinogen (Fg) was completely inhibited by human α2-M. However, the synthetic peptides Tos-Gly-Pro-Lys-pNA and H-D-Pro-Phe-Arg-pNA (S-2302) were hydrolyzed with almost no reduction in rate. At pH 7.4 and 37 °C the proteinase (0.15 μM over 15 min) interacted with α2-M, and each mole of α2-M bound 2 mol of enzyme. Sodium dodecyl sulfate gel electrophoresis of reduced samples showed that the interaction of α2-M with either LV-PA or t-PA preincubated with Plg resulted in the formation of ∼90 kDa fragments and high molecular mass complexes (Mr 180 kDa), generated by the incubation mixture (LV-PA or t-PA) and Plg. The data suggest that LV-PA is a direct-type PA and its fibrinolytic effect can be reduced by α2-M in vivo.

Original languageEnglish
Pages (from-to)490-494
Number of pages5
JournalToxicon
Volume47
Issue number4
DOIs
StatePublished - 15 Mar 2006

Bibliographical note

Funding Information:
This work was supported by Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) Processos CBB 306/2 and EDT- 24000/01.

Keywords

  • Fibrinolysis
  • Lachesis muta
  • Plasminogen activator
  • Serineproteinase
  • α2-macroglobulin

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