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      Oxidative Processes in Glomerulonephritides: Additional Facts

      Nephron

      S. Karger AG

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          Most cited references 6

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          Regulation of gene expression by reactive oxygen.

          Reactive oxygen intermediates are produced in all aerobic organisms during respiration and exist in the cell in a balance with biochemical antioxidants. Excess reactive oxygen resulting from exposure to environmental oxidants, toxicants, and heavy metals perturbs cellular redox balance and disrupts normal biological functions. The resulting imbalance may be detrimental to the organism and contribute to the pathogenesis of disease and aging. To counteract the oxidant effects and to restore a state of redox balance, cells must reset critical homeostatic parameters. Changes associated with oxidative damage and with restoration of cellular homeostasis often lead to activation or silencing of genes encoding regulatory transcription factors, antioxidant defense enzymes, and structural proteins. In this review, we examine the sources and generation of free radicals and oxidative stress in biological systems and the mechanisms used by reactive oxygen to modulate signal transduction cascades and redirect gene expression.
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            Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxynitrite during the respiratory burst of human neutrophils.

            Nitric oxide (.NO) release, oxygen uptake and hydrogen peroxide (H2O2) production elicited by increasing phorbol 12-myristate 13-acetate (PMA) concentrations were measured in human neutrophils. Half-maximal activities were sequentially elicited at about 0.0001-0.001 micrograms PMA/ml (.NO) and 0.001-0.01 micrograms PMA/ml (H2O2). At saturated PMA concentrations, .NO production, oxygen uptake and H2O2 release were 0.56 +/- 0.04, 3.32 +/- 0.52 and 1.19 +/- 0.17 nmol.min-1.10(6) cells-1. .NO production accounts for about 30% of the total oxygen uptake. Luminol-dependent chemiluminescence, reported to detect NO reactions in other inflammatory cells, was also half-maximally activated at about 0.001-0.01 micrograms PMA/ml. Preincubation with NG-monomethyl-L-arginine (L-NMMA) decreased O2 uptake and .NO release but increased H2O2 production, while superoxide dismutase (SOD) increased .NO detection by 30%. Chemiluminescence was also reduced by preincubation with L-NMMA and/or SOD. The results indicate that .NO release is part of the integrated response of stimulated human neutrophils and that, in these cells, kinetics of .NO and O2.- release favour the formation of other oxidants like peroxynitrite.
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              Apoptosis or necrosis: intracellular levels of glutathione influence mode of cell death.

              The effect of lowering intracellular glutathione (GSH) concentrations on the toxicity of alkylating agents, and RNA synthesis inhibitor and topoisomerase 1 and 2 inhibitors to a number of human leukaemic cell lines were evaluated. By using the GSH synthesis inhibitor DL-buthionine-(S,R)-sulfoximine (BSO), GSH levels were artificially reduced. Cells with low GSH concentrations were exposed to a number of cytotoxic agents and the resultant mode of cell death was analysed using morphological and biochemical criteria. It was found that untreated cells exposed to the above drugs underwent apoptosis to varying extents. However, the toxicity of alkylating agents was dramatically increased to all cell lines on lowering GSH levels, with the mode of cell death switching from apoptosis to necrosis. The reduction of GSH levels had no effect on the toxicity of actinomycin-D, camptothecin or etoposide, nor did it affect the mode of cell death induced by these agents. These observations suggest that modulation of GSH levels effect the toxicity of alkylating agents and that GSH influences the mode of cell death induced by alkylating agents.
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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2000
                June 2000
                31 May 2000
                : 85
                : 2
                : 103-106
                Affiliations
                Oxon, UK
                Article
                45641 Nephron 2000;85:103–106
                10.1159/000045641
                10867514
                © 2000 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
                References: 44, Pages: 4
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/45641
                Categories
                Minireview

                Cardiovascular Medicine, Nephrology

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