勒贝他汀是一种来自巨蝰蛇毒液的整合素，可抑制整合素介导的细胞黏附、迁移和血管生成。

Lebestatin, a disintegrin from Macrovipera venom, inhibits integrin-mediated cell adhesion, migration and angiogenesis.

作者信息

Olfa Kallech-Ziri, José Luis, Salma Daoud, Amine Bazaa, Najet Srairi Abid, Nicolas Andreotti, Maxime Lehmann, Raoudha Zouari, Kamel Mabrouk, Jacques Marvaldi, Jean-Marc Sabatier, Mohamed El Ayeb, Naziha Marrakchi

机构信息

Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunis Belvédère, Tunisie.

出版信息

Lab Invest. 2005 Dec;85(12):1507-16. doi: 10.1038/labinvest.3700350.

DOI:10.1038/labinvest.3700350

PMID:16200076

Abstract

Lebestatin, a new member of the lysine-threonine-serine (KTS)-disintegrin family, was purified to homogeneity from Tunisian snake (Macrovipera lebetina) venom. It is a single-chain polypeptide composed of 41 amino acids. The amino-acid sequence of lebestatin shows that it displays a pattern of cysteines similar to other short disintegrins, but contains the sequence KTS rather than RGD in its integrin-binding loop. Lebestatin presents a high homology with obtustatin and viperistatin. Lebestatin interacts specifically with the alpha1beta1 integrin. It was thus able to inhibit both adhesion and migration of PC12 and alpha1beta1 integrin-expressing CHO cells (CHO-alpha1) to type I and IV collagens. This disintegrin also affected adhesion and migration of endothelial cells and exhibited an anti-angiogenic effect in vivo when using the 8-day-old embryo chick chorioallantoic membrane model.

摘要

莱贝他汀是赖氨酸 - 苏氨酸 - 丝氨酸（KTS）- 去整合素家族的新成员，从突尼斯蛇（大蝰蛇）毒液中纯化至同质。它是由41个氨基酸组成的单链多肽。莱贝他汀的氨基酸序列表明，它显示出与其他短去整合素相似的半胱氨酸模式，但在其整合素结合环中含有KTS序列而非RGD序列。莱贝他汀与钝吻他汀和蝰蛇他汀具有高度同源性。莱贝他汀与α1β1整合素特异性相互作用。因此，它能够抑制PC12细胞和表达α1β1整合素的CHO细胞（CHO - α?）对I型和IV型胶原蛋白的粘附和迁移。这种去整合素还影响内皮细胞的粘附和迁移，并在使用8日龄胚胎鸡绒毛尿囊膜模型时在体内表现出抗血管生成作用。