Mechanisms of H2O2-induced oxidative stress in endothelial cells

Christian H Coyle; Luis J Martinez; Mitchell C Coleman; Douglas R Spitz; Neal L Weintraub; Khalid N Kader

doi:10.1016/j.freeradbiomed.2006.02.017

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Mechanisms of H2O2-induced oxidative stress in endothelial cells

Journal article

Peer reviewed

Mechanisms of H2O2-induced oxidative stress in endothelial cells

Christian H Coyle, Luis J Martinez, Mitchell C Coleman, Douglas R Spitz, Neal L Weintraub and Khalid N Kader

Free radical biology & medicine, Vol.40(12), pp.2206-2213

06/15/2006

DOI: 10.1016/j.freeradbiomed.2006.02.017

PMID: 16785034

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Abstract

Hydrogen peroxide, produced by inflammatory and vascular cells, induces oxidative stress that may contribute to endothelial dysfunction. In smooth muscle cells, H(2)O(2) induces production of O(2)*(-) by activating NADPH oxidase. However, the mechanisms whereby H(2)O(2) induces oxidative stress in endothelial cells are poorly understood. We examined the effects of H(2)O(2) on O(2)*(-) levels on porcine aortic endothelial cells (PAEC). Treatment with 60 micromol/L H(2)O(2) markedly increased intracellular O(2)*(-) levels (determined by conversion of dihydroethidium to hydroxyethidium) and produced cytotoxicity (determined by propidium iodide staining) in PAEC. Overexpression of human manganese superoxide dismutase in PAEC reduced O(2)*(-) levels and attenuated cytotoxicity resulting from treatment with H(2)O(2). L-NAME, an inhibitor of nitric oxide synthase (NOS), and apocynin, an inhibitor of NADPH oxidase, reduced O(2)*(-) levels in PAEC treated with H(2)O(2), suggesting that both NOS and NADPH oxidase contribute to H(2)O(2)-induced O(2)*(-) in PAEC. Inhibition of NADPH oxidase using apocynin and NOS rescue with L-sepiapterin together reduced O(2)*(-) levels in PAEC treated with H(2)O(2) to control levels. This suggests interaction-distinct NOS and NADPH oxidase pathways to superoxide. We conclude that H(2)O(2) produces oxidative stress in endothelial cells by increasing intracellular O(2)*(-) levels through NOS and NADPH oxidase. These findings suggest a complex interaction between H(2)O(2) and oxidant-generating enzymes that may contribute to endothelial dysfunction.

Superoxide Dismutase - genetics

Oxidative Stress

Humans

NADPH Oxidases - metabolism

Superoxides - analysis

Nitric Oxide Synthase - antagonists & inhibitors

Endothelium, Vascular - drug effects

Endothelium, Vascular - enzymology

Swine

Acetophenones - pharmacology

Superoxides - metabolism

Aorta - enzymology

Superoxide Dismutase - metabolism

Hydrogen Peroxide - toxicity

NG-Nitroarginine Methyl Ester - pharmacology

Endothelial Cells - metabolism

Aorta - drug effects

NADPH Oxidases - antagonists & inhibitors

Cells, Cultured

Enzyme Inhibitors - pharmacology

Antioxidants - pharmacology

Animals

Nitric Oxide Synthase - metabolism

Aorta - cytology

Endothelial Cells - enzymology

Endothelial Cells - drug effects

Details

Title: Subtitle: Mechanisms of H2O2-induced oxidative stress in endothelial cells
Creators: Christian H Coyle - Cell and Synthetic Interface Engineering Laboratory, Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA
Luis J Martinez
Mitchell C Coleman
Douglas R Spitz
Neal L Weintraub
Khalid N Kader
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.40(12), pp.2206-2213
DOI: 10.1016/j.freeradbiomed.2006.02.017
PMID: 16785034
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Publisher: United States
Grant note: CA-086862 / NCI NIH HHS HL-076684 / NHLBI NIH HHS HL-62984 / NHLBI NIH HHS HL-070860 / NHLBI NIH HHS
Language: English
Date published: 06/15/2006
Academic Unit: Pathology; Orthopedics and Rehabilitation; Radiation Oncology
Record Identifier: 9984040344002771

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