Roles of reactive oxygen species in angiopoietin-1/tie-2 receptor signaling

Rania Harfouche; Nelly Abdel Malak; Ralf P Brandes; Aly Karsan; Kaikobad Irani; Sabah N A Hussain

doi:10.1096/fj.04-3621fje

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Roles of reactive oxygen species in angiopoietin-1/tie-2 receptor signaling

Journal article

Peer reviewed

Roles of reactive oxygen species in angiopoietin-1/tie-2 receptor signaling

Rania Harfouche, Nelly Abdel Malak, Ralf P Brandes, Aly Karsan, Kaikobad Irani and Sabah N A Hussain

The FASEB journal, Vol.19(12), pp.1728-1730

10/2005

DOI: 10.1096/fj.04-3621fje

PMID: 16049136

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Abstract

In this study we identified the involvement of reactive oxygen species (ROS) in signaling and biological effects of the angiopoietin-1 (Ang-1)/tie-2 receptor pathway. Exposure of human umbilical vein endothelial cells to Ang-1 (50 ng/ml) induced rapid and transient production of ROS, particularly superoxide anions. ROS production was attenuated by preincubation with a peptide (gp91ds-tat) that inhibits the association of the gp91(phox) subunit with the p47(phox) subunit of NADPH oxidase and by the expression of a dominant-negative form of Rac-1 (Rac1N17). These results suggest that ROS production in response to Ang-1 exposure originates mainly from a Rac-1-dependent NADPH oxidase. Overexpression of antioxidants (superoxide dismutase and catalase) and Rac1N17, as well as preincubation with selective inhibitors of NADPH oxidase augmented basal p38 phosphorylation, inhibited Ang-1-induced PAK-1 phosphorylation and potentiated Ang-1-induced Erk1/2 phosphorylation but had no influence on AKT and SAPK/JNK phosphorylation by Ang-1. Exposure to Ang-1 (100 ng/ml) for 5 h induced a threefold increase in endothelial cell migration, a response that was strongly inhibited by overexpression of antioxidants, Rac1N17, and selective NADPH oxidase inhibitors. We conclude that activation of tie-2 receptors by Ang-1 triggers the production of ROS through activation of NADPH oxidase and that ROS generation by Ang-1 promotes endothelial cell migration while negatively regulating Erk1/2 phosphorylation.

Endothelium, Vascular - cytology

p21-Activated Kinases

Phosphorylation

Reactive Oxygen Species

Antioxidants - chemistry

Membrane Glycoproteins - metabolism

Antioxidants - metabolism

Humans

NADPH Oxidases - metabolism

Immunoblotting

Angiopoietin-1 - metabolism

Phosphoproteins - metabolism

Transfection

Genes, Dominant

Time Factors

Receptor, TIE-2 - metabolism

p38 Mitogen-Activated Protein Kinases - metabolism

Proto-Oncogene Proteins c-akt - metabolism

Umbilical Veins - cytology

Protein-Serine-Threonine Kinases - metabolism

Superoxide Dismutase - metabolism

Green Fluorescent Proteins - metabolism

Angiopoietins - metabolism

Peptides - chemistry

Signal Transduction

Acridines - metabolism

Cells, Cultured

Enzyme Inhibitors - pharmacology

NADPH Oxidase 2

Catalase - metabolism

Gene Expression Regulation, Enzymologic

Mitogen-Activated Protein Kinase 3 - metabolism

Endothelial Cells - cytology

Protein Binding

Enzyme Activation

Microscopy, Fluorescence

Cell Movement

Mitogen-Activated Protein Kinase 1 - metabolism

Details

Title: Subtitle: Roles of reactive oxygen species in angiopoietin-1/tie-2 receptor signaling
Creators: Rania Harfouche - Critical Care and Respiratory Divisions, Royal Victoria Hospital and Meakins-Christie Laboratories, McGill University, Montreal, Québec, Canada
Nelly Abdel Malak
Ralf P Brandes
Aly Karsan
Kaikobad Irani
Sabah N A Hussain
Resource Type: Journal article
Publication Details: The FASEB journal, Vol.19(12), pp.1728-1730
Publisher: United States
DOI: 10.1096/fj.04-3621fje
PMID: 16049136
ISSN: 0892-6638
eISSN: 1530-6860
Grant note: DOI: 10.13039/100004411, name: Heart and Stroke Foundation of Canada
Language: English
Date published: 10/2005
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984047989102771

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