Xanthine Oxidase-Derived ROS Display a Biphasic Effect on Endothelial Cells Adhesion and FAK Phosphorylation.

Oxid Med Cell Longev

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.

Published: March 2017

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978831PMC
http://dx.doi.org/10.1155/2016/9346242DOI Listing

Publication Analysis

Top Keywords

endothelial cells
12
adhesion fak
12
fak phosphorylation
12
adhesion
9
ros produced
8
study ros
8
hx-xo-derived ros
8
ros induced
8
huvec adhesion
8
stages process
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!