on September 22, 2005
Published online before print September 22, 2005, doi: 10.1161/01.ATV.0000187472.55437.af
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Submitted on May 18, 2005
Accepted on September 14, 2005
IQGAP1 Regulates Reactive Oxygen Species-Dependent Endothelial Cell Migration Through Interacting With Nox2
Satoshi Ikeda ;
From Division of Cardiology (S.I., M.Y.-T., L.H., N.A.P., G.M.A., M.U.-F.), Department of Medicine, Emory University School of Medicine, Atlanta, Ga; and the Department of Veterinary Molecular Biology (M.T.Q.), Montana State University, Bozeman, Mt.
* To whom correspondence should be addressed. E-mail: mfukai{at}emory.edu.
Objective--Endothelial cell (EC) migration is a key event for repair process after vascular injury and angiogenesis. EC migration is regulated by reorganization of the actin cytoskeleton at the leading edge and localized production of reactive oxygen species (ROS) at the site of injury. However, underlying mechanisms are unclear. We reported that IQGAP1, an actin binding scaffold protein, mediates VEGF-induced activation of gp91phox (Nox2)-dependent NAD(P)H oxidase and EC migration. We thus hypothesized that Nox2 and IQGAP1 may play important roles in ROS-dependent EC migration in response to injury.
Methods and Results--Using a monolayer scratch assay with confluent ECs, we show that ROS production is increased at the margin of scratch area and Nox2 translocates to the leading edge, where it colocalizes and associates with both actin and IQGAP1 in migrating ECs. Knockdown of IQGAP1 using siRNA and inhibition of the actin cytoskeleton blocked scratch injury-induced H2O2 production, Nox2 translocation and its interaction with actin, and EC migration toward the injured site.
Conclusions--These suggest that IQGAP1 may function to link Nox2 to actin at the leading edge, thereby facilitating ROS production at the site of injury, which may contribute to EC migration.
Key words: actin cytoskeleton • endothelial cell migration • IQGAP1 • NAD(P)H oxidase • reactive oxygen species
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