Suppressive effect and mechanism of saxatilin, a disintegrin from Korean snake ( Gloydius saxatilis), in vascular smooth muscle cells

RGD-peptides can inhibit the binding of ligands to certain β3 integrins, αIIbβ3 and αvβ3, both of which are involved in neointimal hyperplasia that contributes to atherosclerosis and restenosis of arterial walls. Saxatilin, a disintegrin from a Korean snake ( Gloydius saxatilis), interacts with inte...

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Bibliographic Details
Published in:Toxicon (Oxford) 2008-09, Vol.52 (3), p.474-480
Main Authors: Sohn, Young-Doug, Cho, Kil-Sang, Sun, Sae-Ah, Sung, Hee-Jin, Kwak, Kyu-Won, Hong, Sung-Yu, Kim, Doo-Sik, Chung, Kwang-Hoe
Format: Article
Language:English
Subjects:
Animal poisons toxicology. Antivenoms
Animals
Biological and medical sciences
Cell Adhesion - drug effects
Cell cycle
Cell Cycle - drug effects
Cell Proliferation - drug effects
Cells, Cultured
De-adhesion
Disintegrin
Disintegrins - pharmacology
Extracellular Signal-Regulated MAP Kinases - metabolism
Focal adhesion
Focal Adhesion Protein-Tyrosine Kinases - metabolism
Humans
Integrin
Medical sciences
Muscle, Smooth, Vascular - cytology
Myocytes, Smooth Muscle - drug effects
Proliferation
Saxatilin
Smooth muscle cells
Snake Venoms - chemistry
Toxicology
Viperidae - physiology
αvβ3
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Summary:RGD-peptides can inhibit the binding of ligands to certain β3 integrins, αIIbβ3 and αvβ3, both of which are involved in neointimal hyperplasia that contributes to atherosclerosis and restenosis of arterial walls. Saxatilin, a disintegrin from a Korean snake ( Gloydius saxatilis), interacts with integrins αIIbβ3 and αvβ3. It suppressed the adhesion of human coronary artery smooth muscle cells (HCASMCs) to vitronectin with an IC 50 of 2.5 μM, and growth factor (PDGF-BB or bFGF)-induced proliferation was inhibited at an IC 50 of 25 μM. Saxatilin disassembled the actin cytoskeleton of focal adhesion and induced cell detachment. This disassembly of focal adhesion in saxatilin-treated HCASMCs involved caspase-induced paxillin degradation. Saxatilin temporally phosphorylated FAK and ERKs and affected the cell cycle of HCASMCs by increasing CDK inhibitors (p21 and p27) and reducing cyclins (D1/2 and E). These results may have significant implications for integrin antagonistic therapy used for the treatment of atherosclerosis and restenosis.
ISSN:0041-0101
1879-3150
DOI:10.1016/j.toxicon.2008.06.020