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      Role of Reactive Oxygen Species-Sensitive Extracellular Signal-Regulated Kinase Pathway in Angiotensin II-Induced Endothelin-1 Gene Expression in Vascular Endothelial Cells

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          Abstract

          Background: Circulating angiotensin II (Ang II) increases vascular endothelin-1 (ET-1) tissue levels, which in turn mediate a major part of Ang II-stimulated vascular growth and hypertension in vivo. Ang II also stimulates the generation of reactive oxygen species (ROS) within vascular endothelial cells. However, whether ROS are involved in Ang II-induced ET-1 gene expression, and the related intracellular mechanisms occurring within vascular endothelial cells remain unclear. Methods: Cultured endothelial cells were stimulated with Ang II, and the thus elicited ET-1 gene expression was examined by Northern blotting and a promoter activity assay. Antioxidant pretreatment of endothelial cells was performed prior to Ang II-induced extracellular signal-regulated kinase (ERK) phosphorylation in order to elucidate the redox-sensitive pathway for ET-1 gene expression. Results: The ET-1 gene was induced with Ang II, which was inhibited with Ang II type 1 receptor antagonist (irbesartan). Ang II-enhanced intracellular ROS levels were inhibited by irbesartan and several antioxidants, and antioxidants also suppressed Ang II-induced ET-1 gene expression. Further, Ang II-activated ERK phosphorylation was also significantly inhibited by certain antioxidants. An ERK inhibitor, U0126, inhibited Ang II-induced ET-1 expression completely. Cotransfection of the dominant negative mutant of Ras, Raf and MEK1 (ERK kinase) attenuated the Ang II-enhanced ET-1 promoter activity, suggesting that the Ras/Raf/ERK pathway is required for Ang II-induced ET-1 gene expression. Ang II-induced activator protein-1 (AP-1) reporter activities were inhibited by antioxidants. Moreover, mutational analysis of the ET-1 gene promoter showed that the AP-1 binding site was an important cis element in Ang II-induced ET-1 gene expression. Conclusions: Our data suggest that ROS are involved in Ang II-induced ET-1 gene expression within endothelial cells. The redox-sensitive ERK-mediated AP-1 transcriptional pathway plays an important role in Ang II-induced ET-1 gene expression.

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          Most cited references 15

          • Record: found
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          • Article: not found

          The role of oxidized lipoproteins in atherogenesis

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            • Record: found
            • Abstract: not found
            • Article: not found

            Activation of Mitogen-activated Protein Kinase by HO

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              • Record: found
              • Abstract: found
              • Article: not found

              Increased generation of superoxide by angiotensin II in smooth muscle cells from resistance arteries of hypertensive patients: role of phospholipase D-dependent NAD(P)H oxidase-sensitive pathways.

              We tested the hypothesis that increased responsiveness of phospholipase D (PLD) to angiotensin II (Ang II) is associated with increased oxidative stress and exaggerated growth responses in vascular smooth muscle cells (VSMC) from untreated essential hypertensive patients. VSMCs from peripheral resistance arteries of normotensive and hypertensive subjects were studied. Production of reactive oxygen species (ROS) was measured with the fluoroprobe 5-(and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA). PLD and reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase were assessed with the inhibitors, dihydro-D-erythro-sphingosine (sphinganine) and diphenylene iodinium (DPI), respectively, and protein kinase C (PKC) effects were determined using chelerythrine chloride and calphostin C. PLD activity was measured by the transphosphatidylation assay. Ang II increased the CM-H2DCFDA fluorescence signal, derived predominantly from H2O2. Ang II-induced generation of DPI-inhibitable ROS was significantly enhanced in cells from hypertensives compared with normotensives (Emax = 72 +/- 2 versus 56.9 +/- 1.8 fluorescence units, P< 0.01). PLD inhibition attenuated Ang II-induced ROS generation, with greater effects in the hypertensive group than the normotensive group (delta = 42 +/- 3.3 versus 21 +/- 2 units). PKC inhibition partially decreased Ang II-elicited signals. Ang II-stimulated PLD activity and DNA and protein synthesis were significantly greater in cells from hypertensives than normotensives. These effects were normalized by DPI and sphinganine. Our results suggest that in essential hypertension enhanced oxidative stress and augmented growth-promoting actions of Ang II are associated with increased activation of PLD-dependent pathways. These processes may contribute to vascular remodeling in hypertension.
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                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                2004
                February 2004
                20 February 2004
                : 41
                : 1
                : 64-74
                Affiliations
                aDepartment of Medicine, Taipei Medical University-Wan Fang Hospital, bDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, cDepartment of Medicine, Taipei Medical University Hospital, dDepartment of Cardiac Surgery, Shin Kong Wu Ho-Su Memorial Hospital, eDepartment of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC
                Article
                76247 J Vasc Res 2004;41:64–74
                10.1159/000076247
                14730203
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 7, References: 39, Pages: 11
                Categories
                Research Paper

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