title: Regulation of brain endothelial cells migration and angiogenesis by P-glycoprotein/caveolin-1 interaction.
abstract: We have investigated the involvement of P-glycoprotein (P-gp)/caveolin-1 interaction in the regulation of brain endothelial cells (EC) migration and tubulogenesis. P-gp overexpression in MDCK-MDR cells was correlated with enhanced cell migration whereas treatment with P-gp inhibitors CsA or PSC833 reduced it. Transfection of RBE4 rat brain endothelial cells with mutated versions of MDR1, in the caveolin-1 interaction motif, decreased the interaction between P-gp and caveolin-1, enhanced P-gp transport activity and cell migration. Moreover, down-regulation of caveolin-1 in RBE4 cells by siRNA against caveolin-1 stimulated cell migration. Interestingly, the inhibition of P-gp/caveolin-1 interaction increased also EC tubulogenesis. Furthermore, decrease of P-gp expression by siRNA inhibited EC tubulogenesis. These data indicate that the level of P-gp/caveolin-1 interaction can modulate brain endothelial angiogenesis and P-gp dependent cell migration.
authors.affiliation: Departement de Chimie-Biochimie, Laboratoire de Médecine Moléculaire, Université du Québec à Montréal, CP 8888, Succursale Centre-Ville, Montréal, QC, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Barakat
authors.forename: Sandra
authors.initials: S
authors.lastname: Turcotte
authors.forename: Michel
authors.initials: M
authors.lastname: Demeule
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Lachambre
authors.forename: Anthony
authors.initials: A
authors.lastname: Régina
authors.forename: Loris G
authors.initials: LG
authors.lastname: Baggetto
authors.forename: Richard
authors.initials: R
authors.lastname: Béliveau
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000098:blood supply*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D004285:Dogs; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051242:Caveolin 1; D003524:Cyclosporins; D034741:RNA, Small Interfering; D016572:Cyclosporine; C070272:valspodar