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The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells
- Source :
-
Free Radical Biology & Medicine . Mar2005, Vol. 38 Issue 5, p616-630. 15p. - Publication Year :
- 2005
-
Abstract
- Abstract: Endothelial dysfunction is characterized by increased levels of reactive oxygen species (ROS) and a prothrombotic state. The mechanisms linking thrombosis to ROS production in the endothelium are not well understood. We investigated the role of thrombin in regulating NADPH oxidase-dependent ROS production and expression of its subunit p22phox in the endothelial cell line EaHy926. Thrombin elicited a biphasic increase in ROS generation peaking within 15 min, but also at 3 h. The delayed response was accompanied by increased p22phox mRNA and protein expression. Two-photon confocal laser microscopy showed colocalization between p22phox and ROS production. Antioxidant treatment with vitamin C or diphenyleneiodonium abrogated thrombin-induced ROS production and p22phox expression, whereas H2O2 elevated ROS production and p22phox levels. Both responses were dependent on p38 MAP kinase and phosphatidylinositol-3-kinase (PI3 kinase)/Akt. Finally, p22phox was required for thrombin- or H2O2-stimulated proliferation. These data show that thrombin rapidly increases ROS production in endothelial cells, resulting, via activation of p38 MAP kinase and PI3 kinase/Akt, in upregulation of p22phox accompanied by a delayed increase in ROS generation and enhanced proliferation. These findings suggest a positive feedback mechanism whereby ROS, possibly generated by the NADPH oxidase, lead to elevated levels of p22phox and, thus, sustained ROS generation as is observed in endothelial dysfunction. [Copyright &y& Elsevier]
- Subjects :
- *HEMOSTATICS
*ORGANIC compounds
*CELL lines
*REACTIVE oxygen species
Subjects
Details
- Language :
- English
- ISSN :
- 08915849
- Volume :
- 38
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Free Radical Biology & Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 16205702
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2004.09.036