Identification of α2β1 integrin inhibitor VP-i with anti-platelet properties in the venom of Vipera palaestinae

Toxicon. 2013 Mar 15:64:96-105. doi: 10.1016/j.toxicon.2013.01.001. Epub 2013 Jan 11.

Abstract

Integrins are receptors of the extracellular matrix (ECM), playing a vital role in pathophysiological processes. They bind to ECM ligands like collagens and can mediate wound healing as well as tumor metastasis and thrombosis, thus being a part of cell adhesion and migration as well as platelet aggregation. For this reason, identifying α2β1 integrin-specific antagonists can assist in the development of drugs to treat tumor progression, angiogenesis, and cardiovascular diseases. Snake venoms have been shown to contain antagonists which target collagen-binding integrins. EMS16, rhodocetin, and VP12 are three toxins belonging to the C-type lectin-related protein family and have been proven to inhibit the α2β1 integrin, specifically the α2 integrin A domain. To specifically isolate antagonists targeting the α2β1 integrin A domain, we developed a protocol based on affinity chromatography. Using this novel approach, the toxin VP-i was isolated from Vipera palaestinae venom. We show that VP-i binds to the α2 integrin A domain and that it successfully inhibits adhesion of various cells to type I collagen as well as cell migration. Moreover, our results indicate that VP-i differs structurally from the previously purified VP12, although not functionally, and therefore is a further venom compound which can be utilized for drug development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Fibrosarcoma / drug therapy
  • Humans
  • Integrin alpha2beta1 / antagonists & inhibitors*
  • Integrin alpha2beta1 / metabolism
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / analysis
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / pharmacology*
  • Viper Venoms / chemistry
  • Viper Venoms / metabolism*
  • Viper Venoms / toxicity
  • Viperidae / metabolism*

Substances

  • Integrin alpha2beta1
  • Platelet Aggregation Inhibitors
  • Viper Venoms