A Differential Role for Endocytosis in Receptor-Mediated Activation of Nox1
- 1 March 2010
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 12 (5), 583-593
- https://doi.org/10.1089/ars.2009.2857
Abstract
Internalization of activated receptors to a compartment enriched with NAPDH oxidase and associated signaling molecules is expected to facilitate regulation of redox-mediated signal transduction. The aim of this study was to test the hypothesis that endocytosis is necessary for generation of reactive oxygen species (ROS) by Nox1 and for redox-dependent signaling in smooth muscle cells (SMCs). Within minutes of treatment with tumor necrosis factor (TNF)-α or thrombin, SMCs increased cellular levels of ROS that was inhibited by shRNA to Nox1. Treatment of SMC with TNF-α induced a dynamin-dependent endosomal generation of ROS, whereas thrombin-mediated ROS production did not occur within endosomes and was not prevented by dominant-negative dynamin (dn-dynamin), but instead required transactivation of the epidermal growth factor receptor (EGFR). Activation of the phosphatidylinositol 3-kinase (PI3K)-Akt-activating transcription factor-1 (ATF-1) pathway by TNF-α and thrombin were both Nox1- and dynamin-dependent. In conclusion, we show that formation of specific ligand–receptor complexes results in spatially distinct mechanisms of Nox1 activation and generation of ROS. These findings provide novel insights into the role of compartmentalization for integrating redox-dependent cell signaling. Antioxid. Redox Signal. 12, 583–593.Keywords
This publication has 56 references indexed in Scilit:
- Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide productionFree Radical Biology & Medicine, 2008
- Regulation of ROS signal transduction by NADPH oxidase 4 localizationThe Journal of cell biology, 2008
- Signaling on the endocytic pathwayCurrent Opinion in Cell Biology, 2007
- Superoxide Flux in Endothelial Cells via the Chloride Channel-3 Mediates Intracellular SignalingMolecular Biology of the Cell, 2007
- Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts of endothelial cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- Nox4 Is Required for Maintenance of the Differentiated Vascular Smooth Muscle Cell PhenotypeArteriosclerosis, Thrombosis, and Vascular Biology, 2007
- Inhibition of receptor internalization attenuates the TNFα-induced ROS generation in non-phagocytic cellsBiochemical and Biophysical Research Communications, 2006
- Reactive oxygen species signaling in vascular smooth muscle cellsCardiovascular Research, 2006
- Tumor necrosis factor signalingCell Death & Differentiation, 2003
- G Protein-coupled Receptors Desensitize and Down-regulate Epidermal Growth Factor Receptors in Renal Mesangial CellsPublished by Elsevier BV ,2001