A differential role for endocytosis in receptor-mediated activation of Nox1.
Journal Article (Journal Article)
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)-alpha or thrombin, SMCs increased cellular levels of ROS that was inhibited by shRNA to Nox1. Treatment of SMC with TNF-alpha 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-alpha 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.
Full Text
Duke Authors
Cited Authors
- Miller, FJ; Chu, X; Stanic, B; Tian, X; Sharma, RV; Davisson, RL; Lamb, FS
Published Date
- March 1, 2010
Published In
Volume / Issue
- 12 / 5
Start / End Page
- 583 - 593
PubMed ID
- 19737091
Pubmed Central ID
- PMC2861543
Electronic International Standard Serial Number (EISSN)
- 1557-7716
Digital Object Identifier (DOI)
- 10.1089/ars.2009.2857
Language
- eng
Conference Location
- United States