Identification of ¦Á2¦Â1 integrin inhibitor VP-i with anti-platelet properties in the venom of Vipera palaestinae

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• 作者：Franziska T. Arlinghaus^a ; ^{arlinghaus@med.uni-frankfurt.de} ; Tatjana Momic^b ; Narmeen Abu Ammar^b ; ^c ; Ela Shai^c ; Galia Spectre^c ; David Varon^c ; Cezary Marcinkiewicz^d ; Heinrich Heide^e ; Philip Lazarovici^b ; Johannes A. Eble^a ; ^{eble@med.uni-frankfurt.de}
• 关键词：VP12 ; Integrin ¦Á2¦Â1 ; A domain ; C-type lectin-related protein
• 刊名：Toxicon
• 出版年：2013
• 出版时间：15 March, 2013
• 年：2013
• 卷：64
• 期：Complete
• 页码：96-105
• 全文大小：1008 K

文摘

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 ¦Á2¦Â1 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 ¦Á2¦Â1 integrin, specifically the ¦Á2 integrin A domain.

To specifically isolate antagonists targeting the ¦Á2¦Â1 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 ¦Á2 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.