Lebestatin, a disintegrin from Macrovipera venom, inhibits integrin-mediated cell adhesion, migration and angiogenesis.
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.
Olfa
Kallech-Ziri
KZ
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunis Belvédère, Tunisie.
José
Luis
L
Salma
Daoud
D
Amine
Bazaa
B
Najet
Srairi Abid
SA
Nicolas
Andreotti
A
Maxime
Lehmann
L
Raoudha
Zouari
Z
Kamel
Mabrouk
M
Jacques
Marvaldi
M
Jean-Marc
Sabatier
S
Mohamed
El Ayeb
el A
Naziha
Marrakchi
M
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002642:Chick Embryo; D006224:Cricetinae; D003412:Cricetulus; D019483:Disintegrins / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D039222:Integrin alpha1beta1 / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D014757:Viper Venoms / Q000737:chemistry*; D017819:Viperidae
D019483:Disintegrins; D039222:Integrin alpha1beta1; D014757:Viper Venoms