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Role of NADPH oxidase-mediated superoxide production in the regulation of E-selectin expression by endothelial cells subjected to anoxia/reoxygenation.

Abstract：

OBJECTIVE:Anoxia followed by reoxygenation (A/R) increases endothelial cell superoxide (O2-) generation which is implicated in E-selectin overexpression. The mechanisms which govern these processes are not fully understood and therefore the goal of our study was to determine the functional importance of NADPH oxidase in the regulation of E-selectin expression in human umbilical veins endothelial cells (HUVECs) submitted to A/R. METHODS:O2- production was estimated using lucigenin chemiluminescence and formazan accumulation. NADPH oxidase expression in HUVECs was studied by RT-PCR and Western blot and E-selectin by Northern blot analysis. NFkappaB activation was assessed by electrophoretic mobility shift assay. RESULTS:A/R caused an increased O2- production which was inhibited by the superoxide dismutase mimetic M40403 (50 micromol/l), the protein kinase C inhibitor chelerythrine (10 micromol/l), the NADPH oxidase inhibitor diphenyleneiodonium (DPI, 10 micromol/l) and the NADPH oxidase assembly blocker apocynin (600 micromol/l). At the end of the anoxic period, the mRNA expression and the protein p47phox was increased as compared to normoxic HUVECs. NFkappaB activation of anoxic HUVECs was maximal after 1 h of reoxygenation and returned to basal normoxic levels after 2 h of reoxygenation. Apocynin reduced the NFkappaB activation at 1 h of reoxygenation. E-selectin mRNA expression was increased after 3 h of reoxygenation of anoxic HUVECs and the SOD mimetic M40403 as well as apocynin prevented this overexpression. CONCLUSIONS:Activated NADPH oxidase is a critical enzyme in E-selectin overexpression after A/R of HUVECs. Moreover, A/R increased expression of membranous and cytosolic NADPH oxidase subunits as well as the protein p47phox. Strategies aimed at preventing endothelial NADPH oxidase activation and/or activity may be useful in controlling leukocyte adhesion during ischemia/reperfusion.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Rupin A,Paysant J,Sansilvestri-Morel P,Lembrez N,Lacoste JM,Cordi A,Verbeuren TJ

doi

10.1016/j.cardiores.2004.03.018

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

323-30

issue

eissn

0008-6363

issn

1755-3245

pii

S0008636304001476

journal_volume

pub_type

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Role of NADPH oxidase-mediated superoxide production in the regulation of E-selectin expression by endothelial cells subjected to anoxia/reoxygenation.