Regulation of endothelial NADPH oxidase by the cytoskeleton

$438,325P01FY2007HLNIH

University Of Chicago, Chicago IL

Investigators

Linked publications & trials

Paper 35856787 Paper 33243842 Paper 29480069 Paper 29343719 Paper 29337590 Paper 29075667 Paper 29075042 Paper 28680579 Paper 27879274 Paper 27543902 Paper 27529643 Paper 27473658 Paper 27442243 Paper 27313980 Paper 26729554 Paper 26697178 Paper 26697169 Paper 26604306 Paper 26596768 Paper 26572585 Paper 26496151 Paper 26432864 Paper 26412935 Paper 26361873 Paper 26272033 Paper 26111161 Paper 26086333 Paper 25862132 Paper 25795725 Paper 25480336 Paper 25271083 Paper 25072537 Paper 25029266 Paper 25006447 Paper 24851274 Paper 24801999 Paper 24634221 Paper 24477234 Paper 24428690 Paper 24416715 Paper 24370952 Paper 24335440 Paper 24053186 Paper 24050723 Paper 24028293 Paper 23911438 Paper 23748834 Paper 23729486 Paper 23720293 Paper 23667561 Paper 23662180 Paper 23583905 Paper 23526214 Paper 23523769 Paper 23492194 Paper 23449739 Paper 23306835 Paper 23296034 Paper 23212923 Paper 23056240 Paper 22931549 Paper 22790920 Paper 22771388 Paper 22728435 Paper 22683568 Paper 22592920 Paper 22511173 Paper 22345573 Paper 22303475 Paper 22235241 Paper 22219181 Paper 22213015 Paper 22047509 Paper 22015949 Paper 22008516 Paper 21997484 Paper 21925517 Paper 21864676 Paper 21765345 Paper 21741394 Paper 21732359 Paper 21617203 Paper 21596828 Paper 21570987 Paper 21543796 Paper 21520057 Paper 21478254 Paper 21443946 Paper 21441351 Paper 21420028 Paper 21337123 Paper 21297081 Paper 21156980 Paper 21146549 Paper 21111731 Paper 21071472 Paper 21045234 Paper 20883826 Paper 20861316 Paper 20729389

Abstract

While differences between vascular and phagocytic NADPH oxidase are yet to be identified, reactive oxygen species (ROS) have emerged as important regulatory molecules which function as critical second messengers modulating signal transduction pathways involved in endothelial cell growth, migration, adhesion and barrier function. While actin cytoskeleton has been implicated in phagocytosis and oxidative burst in neutrophils, very little is known regarding the role of actin cytoskeleton in endothelial NAD[P]H oxidase assembly and activation. Our preliminary studies demonstrate that acute hyperoxia-mediated activation of NAD[P]H oxidase and enhanced production of superoxide is regulated by cortical actin cytoskeleton rearrangement, phosphorylated myosin light chain, small G-proteins and phosphatidic acid. We hypothesize that acute hyperoxia-induced endothelial NAD[P]H oxidase activation is mediated by signal transduction pathways regulating cortical actin cytoskeleton remodeling and by facilitating the assembly of the oxidase sub-components. The following specific aims will investigate the relationship between acute hyperoxia, actin cytoskeletal remodeling and NAD[P]H oxidase assembly and activation in human pulmonary artery endothelial cells in the absence of cytotoxicity. SA#1: Will investigate pathways linking actin cytoskeleton remodeling in NAD[P]H oxidase activation; SA#2: Will characterize the role of myosin light-chain phosphorylation in NAD[P]H oxidase activation; SA#3: Will define the role of cortactin and coronin in endothelial NAD[P]H oxidase activation and SA#4: Will characterize the role of phospholipase D / phosphatidic acid signaling in endothelial NAD[P]H oxidase activation. An understanding of the role of actin cytoskeletal remodeling in NAD[P]H oxidase assembly and activation will allow development of targeted therapies to modulate ROS-induced signaling and prevent lung injury and endothelial dysfunction.

View original record on NIH RePORTER →