The Actin Cytoskeleton Reorganization Induced by Rac1 Requires the Production of Superoxide

Leni Moldovan, Kaikobad Irani, Nicanor I. Moldovan, Toren Finkel, Pascal Goldschmidt-Clermont

Research output: Contribution to journalArticle

68 Citations (Scopus)

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 β-galactosidase (Ad-βGal). 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 AdracV12-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.

Original languageEnglish
Pages (from-to)29-43
Number of pages15
JournalAntioxidants and Redox Signaling
Volume1
Issue number1
StatePublished - Mar 1 1999
Externally publishedYes

Fingerprint

Actin Cytoskeleton
Superoxides
Actins
Endothelial cells
Endothelial Cells
Superoxide Dismutase
Free Radicals
Galactosidases
Acetylcysteine
Membranes
Monomeric GTP-Binding Proteins
NADPH Oxidase
Phagocytes
Fluorescent Dyes
Cysteine
Fibroblasts
Viruses
Antioxidants
Chemical activation
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Moldovan, L., Irani, K., Moldovan, N. I., Finkel, T., & Goldschmidt-Clermont, P. (1999). The Actin Cytoskeleton Reorganization Induced by Rac1 Requires the Production of Superoxide. Antioxidants and Redox Signaling, 1(1), 29-43.

The Actin Cytoskeleton Reorganization Induced by Rac1 Requires the Production of Superoxide. / Moldovan, Leni; Irani, Kaikobad; Moldovan, Nicanor I.; Finkel, Toren; Goldschmidt-Clermont, Pascal.

In: Antioxidants and Redox Signaling, Vol. 1, No. 1, 01.03.1999, p. 29-43.

Research output: Contribution to journalArticle

Moldovan, L, Irani, K, Moldovan, NI, Finkel, T & Goldschmidt-Clermont, P 1999, 'The Actin Cytoskeleton Reorganization Induced by Rac1 Requires the Production of Superoxide', Antioxidants and Redox Signaling, vol. 1, no. 1, pp. 29-43.
Moldovan L, Irani K, Moldovan NI, Finkel T, Goldschmidt-Clermont P. The Actin Cytoskeleton Reorganization Induced by Rac1 Requires the Production of Superoxide. Antioxidants and Redox Signaling. 1999 Mar 1;1(1):29-43.
Moldovan, Leni ; Irani, Kaikobad ; Moldovan, Nicanor I. ; Finkel, Toren ; Goldschmidt-Clermont, Pascal. / The Actin Cytoskeleton Reorganization Induced by Rac1 Requires the Production of Superoxide. In: Antioxidants and Redox Signaling. 1999 ; Vol. 1, No. 1. pp. 29-43.
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