IQGAP1 regulates reactive oxygen species-dependent endothelial cell migration through interacting with Nox2

Satoshi Ikeda, Minako Yamaoka-Tojo, Lula Hilenski, Nikolay A. Patrushev, Ghulam M. Anwar, Mark T. Quinn, Masuko Ushio-Fukai

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

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 H 2O2 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.

Original languageEnglish (US)
Pages (from-to)2295-2300
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number11
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

Keywords

  • Actin cytoskeleton
  • Endothelial cell migration
  • IQGAP1
  • NAD(P)H oxidase
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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