Snake venom disintegrin, saxatilin, inhibits platelet aggregation, human umbilical vein endothelial cell proliferation, and smooth muscle cell migration.
A novel disintegrin, saxatilin, was purified from Korean snake (Gloydius saxatilis) venom by means of chromatographic fractionations. We have also isolated the cDNA encoding the disintegrin using cDNA library of the snake venom gland and analyzed its complete nucleotide sequence. Saxatilin is a single-chain polypeptide composed of 73 amino acids including 12 cysteines as well as the tripeptide sequence Arg-Gly-Asp (RGD), a proposed recognition site of adhesive proteins. Molecular mass of saxatilin was determined to be 7712 Da by matrix-assisted laser desorption ionization mass spectrometry. Saxatilin inhibits glycoprotein (GP) IIb-IIIa binding to immobilized fibrinogen with IC(50) of 2.0 nM and ADP-induced platelet aggregation with IC(50) of 127 nM, respectively. The snake venom disintegrin also significantly suppresses basic fibroblast growth factor-induced human umbilical vein endothelial cell (HUVEC) proliferation, but has little effect on normal growth of the cell. Interaction of human umbilical vein cell to immobilized vitronectin is also inhibited by binding of saxatilin to alpha(v)beta(3) integrin. Adhesion of smooth muscle cells (SMCs) to vitronectin as well as vitronectin-induced migration of the cells was strongly inhibited by saxatilin. Several lines of experimental evidence suggest potential use of saxatilin for development of therapeutic agents.
Hong
Sung-Yu
SY
Department of Biochemistry, College of Science, and Bioproducts Research Center, Yonsei University, Seoul 120-749, South Korea.
Koh
You-Seok
YS
Chung
Kwang-Hoe
KH
Kim
Doo-Sik
DS
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D019483:Disintegrins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D004336:Drug Antagonism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005340:Fibrinogen / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology; D019096:Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism
D019483:Disintegrins; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019096:Vitronectin; C459080:saxatilin; D016222:Fibroblast Growth Factor 2; D005340:Fibrinogen