The snake venom disintegrin salmosin induces apoptosis by disassembly of focal adhesions in bovine capillary endothelial cells.
Salmosin, a disintegrin purified from a Korean snake (Agkistrodon halys brevicaudus) venom, interacts with integrin alpha(v)beta(3) and inhibits the proliferation of bovine capillary endothelial (BCE) cells induced by basic fibroblast growth factor (bFGF). We investigated salmosin's mechanism of inhibition of BCE cell proliferation by examining changes in the cytoskeleton and activation of integrin-mediated signaling molecules. Salmosin disassembled cortical actins at focal adhesions and induced cells to be rounded and detached, but it did not alter microtubule structures in the early stage of cells being rounded. Immunolocalization of paxillin also demonstrated that focal adhesions were disassembled by salmosin. In salmosin-treated BCE cells, focal adhesion kinase (FAK) was dephosphorylated and expression of paxillin and p130(CAS) was decreased, but PI3 kinase, ILK, and beta-catenin were not expressed in decreased amounts or modified, suggesting that salmosin inactivated FAK-dependent integrin signaling pathways. While BCE cells proliferated normally on plates coated with salmosin, cells treated with salmosin eventually underwent apoptosis. These observations strongly suggest that salmosin disorganizes focal contacts to detach cells by competing with the extracellular matrix (ECM) for direct binding to integrin alpha(v)beta(3) on the cell surface, eventually leading to apoptosis.
Hong
Sung-Yu
SY
BioBud Co., Ltd., Seoul 120-110, Republic of Korea.
Lee
Hyeryung
H
You
Weon-Kyoo
WK
Chung
Kwang-Hoe
KH
Kim
Doo-Sik
DS
Song
Kiwon
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002196:Capillaries / Q000187:drug effects*; D002417:Cattle; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein; D003435:Crotalid Venoms / Q000378:metabolism* / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects*; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D051419:Paxillin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D051176:beta Catenin; D000099200:Scaffold Protein ILK
D000199:Actins; D050719:Crk-Associated Substrate Protein; D003435:Crotalid Venoms; D003598:Cytoskeletal Proteins; D016222:Fibroblast Growth Factor 2; D051419:Paxillin; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D015534:Trans-Activators; D014404:Tubulin; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C115393:salmosin