Vascular endothelial growth factor induces manganese-superoxide dismutase expression in endothelial cells by a Rac1-regulated NADPH oxidase-dependent mechanism

M R Abid; J C Tsai; K C Spokes; S S Deshpande; K Irani; W C Aird

doi:10.1096/fj.01-0338fje

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Vascular endothelial growth factor induces manganese-superoxide dismutase expression in endothelial cells by a Rac1-regulated NADPH oxidase-dependent mechanism

Journal article

Peer reviewed

Vascular endothelial growth factor induces manganese-superoxide dismutase expression in endothelial cells by a Rac1-regulated NADPH oxidase-dependent mechanism

M R Abid, J C Tsai, K C Spokes, S S Deshpande, K Irani and W C Aird

The FASEB journal, Vol.15(13), pp.2548-2550

11/2001

DOI: 10.1096/fj.01-0338fje

PMID: 11641265

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Abstract

Vascular endothelial growth factor (VEGF) is a potent vascular endothelial cell-specific mitogen that modulates endothelial cell function. In the present study, we show that VEGF induces manganese-superoxide dismutase (MnSOD) mRNA and protein in human coronary artery endothelial cells (HCAEC) and pulmonary artery endothelial cells. VEGF-mediated induction of MnSOD mRNA was inhibited by pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium (DPI), and 4-(2-aminoethyl)-benzenesulfonyl fluoride, but not with the nitric oxide synthase inhibitor L-NAME (N-monomethyl-L-arginine) or the xanthine oxidase inhibitor allopurinol. VEGF stimulation of MnSOD was also inhibited by adenoviral-mediated overexpression of catalase Cu, Zn-SOD and a dominant-negative form of the small GTPase component of NADPH oxidase Rac1 (Rac1N17). Treatment of HCAEC with VEGF resulted in a transient increase in ROS production at 20 min, as measured by 2,7-dichlorodihydrofluorescein oxidation. This effect was abrogated by expression of Rac1N17. Taken together, these findings suggest that VEGF induces MnSOD by an NADPH oxidase-dependent mechanism and that VEGF signaling in the endothelium is coupled to the redox state of the cell.

Endothelium, Vascular - cytology

Free Radical Scavengers - pharmacology

Gene Expression Regulation, Enzymologic - drug effects

Vascular Endothelial Growth Factor A

Superoxide Dismutase - genetics

Reactive Oxygen Species - metabolism

Vascular Endothelial Growth Factors

Humans

NADPH Oxidases - metabolism

Endothelium, Vascular - drug effects

Endothelial Growth Factors - pharmacology

RNA, Messenger - metabolism

Dose-Response Relationship, Drug

Adenoviridae - genetics

Lymphokines - pharmacology

Superoxide Dismutase - metabolism

RNA, Messenger - drug effects

Catalase - genetics

NADPH Oxidases - antagonists & inhibitors

RNA, Messenger - genetics

Cells, Cultured

Superoxide Dismutase - drug effects

Blotting, Western

Genetic Vectors - genetics

Catalase - metabolism

Blotting, Northern

rac1 GTP-Binding Protein - physiology

Endothelium, Vascular - metabolism

rac1 GTP-Binding Protein - genetics

Details

Title: Subtitle: Vascular endothelial growth factor induces manganese-superoxide dismutase expression in endothelial cells by a Rac1-regulated NADPH oxidase-dependent mechanism
Creators: M R Abid - Departments of Medicine and Molecular Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 01125, USA
J C Tsai
K C Spokes
S S Deshpande
K Irani
W C Aird
Resource Type: Journal article
Publication Details: The FASEB journal, Vol.15(13), pp.2548-2550
Publisher: United States
DOI: 10.1096/fj.01-0338fje
PMID: 11641265
ISSN: 0892-6638
eISSN: 1530-6860
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: HL63609-01, HL60585-04, HL65216-01
Language: English
Date published: 11/2001
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Internal Medicine
Record Identifier: 9984047711402771

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