Journal article
The Actin Cytoskeleton Reorganization Induced by Rac1 Requires the Production of Superoxide
Antioxidants & redox signaling, Vol.1(1), pp.29-43
03/1999
DOI: 10.1089/ars.1999.1.1-29
PMID: 11225730
Abstract
The small GTPase rac1 controls actin redistribution to membrane ruffles in fibroblasts and other cell types, as well as the activation of the NADPH oxidase in phagocytes. We explored the possibility that these two processes could be related. We used a replication-deficient adenoviral vector to overexpress the constitutively active form of rac1, racV12, in human and mouse aortic endothelial cells. We show here that, in addition to membrane ruffle formation, racV12 induced an increase in the total amount of F-actin within endothelial cells. Concurrently, racV12-overexpressing cells produced significantly higher amounts of free radicals, as detected by the fluorescent probe 5-(and-6)-chloromethyl-2',7'-dichloro-dihydrofluorescein diacetate, than cells infected with a control virus encoding the bacterial beta-galactosidase (Ad-betaGal). To assess the specific role of superoxide in racV12-induced actin reorganization, we co-expressed the human enzyme Cu,Zn-superoxide dismutase (SOD), by means of another adenoviral vector construct. Overexpressed SOD reduced the concentration of superoxide detected in Ad-racV12-transfected cells and reversed the effects of Ad-racV12 on the content of filamentous actin. MnTMPyP, an SOD mimetic, as well as the antioxidant N-acetyl cysteine, had similar effects, in that they reduced not only the free radicals production, but also ruffle formation and the concentration of F-actin within racV12-overexpressing endothelial cells. Our data support the hypothesis that superoxide is one of the important mediators acting downstream of rac1 on the pathway of actin cytoskeleton remodeling in endothelial cells.
Details
- Title: Subtitle
- The Actin Cytoskeleton Reorganization Induced by Rac1 Requires the Production of Superoxide
- Creators
- Leni Moldovan - Heart and Lung Institute and Division of Cardiology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210Kaikobad Irani - Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287Nicanor I Moldovan - Heart and Lung Institute and Division of Cardiology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210Toren Finkel - Cardiology Branch, National Heart, Blood, and Lung Institute, National Institutes of Health, Bethesda, Maryland 20892Pascal J Goldschmidt-Clermont - Heart and Lung Institute and Division of Cardiology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.1(1), pp.29-43
- DOI
- 10.1089/ars.1999.1.1-29
- PMID
- 11225730
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Language
- English
- Date published
- 03/1999
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984047616002771
Metrics
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