Cell adhesion and integrin expression are modulated by oxidative stress in EA.hy 926 cells.
The effects of oxidative stress on integrin-mediated cell adhesion to the extracellular matrix (ECM) and related apoptosis were investigated using the EA.hy926 endothelial cells treated (or not) with two oxidants: the hypoxanthine/xanthine oxidase system (HX/XO) or the tert-butyl hydroperoxide (t-BHP) which both increased cell apoptosis. Cell adhesion onto vitronectin (Vn) and fibronectin (Fn) was increased at low concentrations of HX/XO (up to 5 mU/ml) or t-BHP (up to 125 microM) and prevented ROS-induced apoptosis. Flow cytometry analysis of integrin expression showed that the expression of integrin alphav and alpha5 subunits was, respectively, increased and decreased. Cell adhesion inhibition experiments using function-blocking monoclonal antibodies against integrin subunits indicated that alphavbeta1 and alphavbeta3 integrins were involved in adhesion of cells to Vn, and alphavbeta3 integrin played a major role in oxidant-treated cells. For adhesion to Fn, alpha5beta1 and alphavbeta1 integrins were required for oxidant-treated cells. Taken together, the results suggest that reactive oxygen species (ROS) produced either by HX/XO or t-BHP could affect expression and/or activation of specific integrins in the interaction of EA.hy926 cells with ECM.
Lamari
Foudil
F
Laboratoire de Biochimie Générale et de Glycobiologie, U.F.R. des Sciences Pharmaceutiques et Biologiques, Université paris, 5 René Descartes, Paris, France.
Braut-Boucher
Francoise
F
Pongnimitprasert
Nushjira
N
Bernard
Maguy
M
Foglietti
Marie-Jose
MJ
Derappe
Christian
C
Aubery
Michele
M
D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D019271:Hypoxanthine / Q000494:pharmacology; D016023:Integrins / Q000235:genetics*; D007700:Kinetics; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D019820:Xanthine / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D016023:Integrins; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D019820:Xanthine; D019271:Hypoxanthine; D020122:tert-Butylhydroperoxide