title: Xanthine Oxidase-Derived ROS Display a Biphasic Effect on Endothelial Cells Adhesion and FAK Phosphorylation.
abstract: In pathological situations such as ischemia-reperfusion and acute respiratory distress syndrome, reactive oxygen species (ROS) are produced by different systems which are involved in endothelial cells injury, ultimately leading to severe organ dysfunctions. The aim of this work was to study the effect of ROS produced by hypoxanthine-xanthine oxidase (Hx-XO) on the adhesion of human umbilical vein endothelial cells (HUVEC) and on the signaling pathways involved. Results show that Hx-XO-derived ROS induced an increase in HUVEC adhesion in the early stages of the process (less than 30 min), followed by a decrease in adhesion in the later stages of the process. Interestingly, Hx-XO-derived ROS induced the same biphasic effect on the phosphorylation of the focal adhesion kinase (FAK), a nonreceptor tyrosine kinase critical for cell adhesion, but not on ERK1/2 phosphorylation. The biphasic effect was not seen with ERK1/2 where a decrease in phosphorylation only was observed. Wortmannin, a PI3-kinase inhibitor, inhibited ROS-induced cell adhesion and FAK phosphorylation. Orthovanadate, a protein tyrosine phosphatase inhibitor, and Resveratrol (Resv), an antioxidant agent, protected FAK and ERK1/2 from dephosphorylation and HUVEC from ROS-induced loss of adhesion. This study shows that ROS could have both stimulatory and inhibitory effects on HUVEC adhesion and FAK phosphorylation and suggests that PI3-kinase and tyrosine phosphatase control these effects.
authors.affiliation: Veterinary National Superior School of Algiers, BP 161, Hacène Badi, El Harrach, 16200 Algiers, Algeria; INSERM-U1149, CNRS-ERL 8252, Centre de Recherche sur l'Inflammation, 75018 Paris, France; Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Site Xavier Bichat, 75018 Paris, France.
authors.forename: Meriem H
authors.identifier: 0000-0003-4202-5364
authors.initials: MH
authors.lastname: Ben-Mahdi
authors.affiliation: INSERM-U1149, CNRS-ERL 8252, Centre de Recherche sur l'Inflammation, 75018 Paris, France; Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Site Xavier Bichat, 75018 Paris, France.
authors.forename: Pham My-Chan
authors.initials: PM
authors.lastname: Dang
authors.affiliation: INSERM-U1149, CNRS-ERL 8252, Centre de Recherche sur l'Inflammation, 75018 Paris, France; Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Site Xavier Bichat, 75018 Paris, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Gougerot-Pocidalo
authors.affiliation: INSERM-U1149, CNRS-ERL 8252, Centre de Recherche sur l'Inflammation, 75018 Paris, France; Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Site Xavier Bichat, 75018 Paris, France.
authors.forename: Yvonne
authors.identifier: 0000-0002-0027-9131
authors.initials: Y
authors.lastname: O'Dowd
authors.affiliation: INSERM-U1149, CNRS-ERL 8252, Centre de Recherche sur l'Inflammation, 75018 Paris, France; Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Site Xavier Bichat, 75018 Paris, France.
authors.forename: Jamel
authors.identifier: 0000-0001-5733-216X
authors.initials: J
authors.lastname: El-Benna
authors.affiliation: INSERM-U1149, CNRS-ERL 8252, Centre de Recherche sur l'Inflammation, 75018 Paris, France; Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Site Xavier Bichat, 75018 Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pasquier
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019271:Hypoxanthine / Q000494:pharmacology; D047468:Immunoprecipitation; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D000077191:Wortmannin; D014969:Xanthine Oxidase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000730:Androstadienes; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019271:Hypoxanthine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017382:Reactive Oxygen Species; D000077185:Resveratrol; D013267:Stilbenes; D000077191:Wortmannin; D014969:Xanthine Oxidase