Involvement of specific integrins in apoptosis induced by vascular apoptosis-inducing protein 1.
Hemorrhagic snake venom induces apoptosis in vascular endothelial cells (VEC). In previous reports, we described the purification and cDNA cloning from Crotalus atrox of vascular apoptosis-inducing protein 1 (VAP1) that specifically induces apoptosis in VEC. VAP1 belongs to the metalloprotease/disintegrin family. Yet the mechanism of inducing apoptosis by VAP1 is still not known. Since other various metalloproteases and disintegrins in snake venoms are known to influence extracellular matrix and cell adhesion, we investigated here the involvement of these adhesion molecules in VAP1-induced apoptosis. Consequently, VAP1 induced apoptosis without degrading extracellular matrix or inhibiting adhesion of VEC. However, VAP1-induced apoptosis was inhibited by antibodies for integrin alpha3, alpha6, beta1. Additionally, apoptosis was inhibited by antibody for CD9, an integrin associated protein. These results suggest that integrins are involved in VAP1-induced apoptosis by some specific role rather than that of adhesion to extracellular matrix.
Araki
Satohiko
S
Marine Biological Laboratory, Graduate School of Science, Nagoya University, Toba, 517-0004, Mie, Japan. saraki@bio.nagoya-u.ac.jp
Masuda
Shinako
S
Maeda
Hiroki
H
Ying
Miao Jun
MJ
Hayashi
Hiroshi
H
D000818:Animals; D023102:Anoikis / Q000187:drug effects; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002448:Cell Adhesion / Q000187:drug effects; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism; D003435:Crotalid Venoms / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D039422:Integrin alpha3; D039503:Integrin alpha6; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D008666:Metalloendopeptidases / Q000235:genetics / Q000494:pharmacology*
D000906:Antibodies; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D003435:Crotalid Venoms; D039422:Integrin alpha3; D039503:Integrin alpha6; D019012:Integrin beta1; D016023:Integrins; D003094:Collagen; D008666:Metalloendopeptidases; C417254:vascular apoptosis-inducing protein 1, Crotalus atrox