Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox is critical for alpha-platelet-derived growth factor receptor-induced production of reactive oxygen species.

Platelet-derived growth factor (PDGF) plays a critical role in the pathogenesis of proliferative diseases. NAD(P)H oxidase (Nox)-derived reactive oxygen species (ROS) are essential for signal transduction by growth factor receptors. Here we investigated the dependence of PDGF-AA-induced ROS production on the cytosolic Nox subunits Rac-1 and p47(phox), and we systematically evaluated the signal relay mechanisms by which the alphaPDGF receptor (alphaPDGFR) induces ROS liberation.

Down-regulation of Rac-1 GTPase by Estrogen.

Rac1 GTPase is essential for the activation of the NAD(P)H oxidase complex and, thereby, regulates the release of reactive oxygen species (ROS) in the vessel wall. 17 beta-estradiol (E2) inhibits vascular ROS production. To elucidate the underlying molecular mechanisms we investigated the potential regulation of Rac1 by E2 in vascular smooth muscle cells.

Impact of HMG CoA reductase inhibition on small GTPases in the heart.

Objective: Members of the Rho GTPase family, Rac1 and RhoA have been suggested to be mediators of cardiac hypertrophy in mice. Rho proteins are posttranslationally isoprenylated. In addition to cholesterol-lowering, statins inhibit the isoprenylation of small G proteins.

Cellular antioxidant effects of atorvastatin in vitro and in vivo.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may exert direct effects on vascular cells and beneficially influence endothelial dysfunction. Because reactive oxygen species (ROS) may lead to vascular damage and dysfunction, we investigated the effect of atorvastatin on ROS production and the underlying mechanisms in vitro and in vivo. Cultured rat aortic vascular smooth muscle cells were incubated with 10 micromol/L atorvastatin.