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      Hydrogen Peroxide Induces Necrosis, Apoptosis, Oncosis and Apoptotic Oncosis of Mouse Terminal Proximal Straight Tubule Cells

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          Abstract

          Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) has been shown to be an important mediator of ischemic and toxic tubular damage. The purpose of this study was to identify the mode of cell death observed in H<sub>2</sub>O<sub>2</sub>-exposed cultures of mouse terminal proximal straight tubule (S<sub>3</sub>) cells. H<sub>2</sub>O<sub>2</sub> induced a dose- and time-dependent decrease in viability of S<sub>3</sub> cells. Morphologically, S<sub>3</sub> cells exposed to H<sub>2</sub>O<sub>2</sub> (0.05–0.1 mM) showed features of necrosis, apoptosis, oncosis and apoptotic oncosis, whereas necrosis occurred most frequently in every experimental condition tested. On the other hand, agarose gel electrophoresis of DNA extracted from S<sub>3</sub> cells exposed to H<sub>2</sub>O<sub>2</sub> revealed a typical DNA ladder pattern. These data suggest that H<sub>2</sub>O<sub>2</sub>-induced proximal tubule damages are associated with the induction of various modes of cell death including necrosis, apoptosis, oncosis and apoptotic oncosis, and with the activation of endonuclease.

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          Most cited references 3

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          Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth.

           K Sudo,  T. Fujita,  J Folkman (1990)
          Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects.
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            Cell death in human atherosclerotic plaques involves both oncosis and apoptosis.

             M Crisby (1997)
            The aim of the present study was to analyze the frequency and mechanism of cell-death in atherosclerotic plaques with a recent history ( 70% diameter reduction undergoing carotid endarterectomy. In situ tailing and nick translation of fragmented DNA, agarose gel electrophoresis of plaque DNA and electron microscopy were used to identify cell death by apoptosis (programmed cell death) and oncosis. The mean number of cells containing fragmented DNA in the plaques was 12.7 +/- 3.5% (n = 15). Focal accumulations of cells with DNA fragmentation occurred in the fibrous cap, at sites of rupture, close to lipid deposits and necrosis and was always accompanied by the presence of inflammatory cells. Electrophoretic separation of DNA isolated from part of plaques, where the presence of DNA fragmentation had previously been demonstrated by in situ DNA nick translation, resulted in multiple ladders of 180-200 base pairs characteristic of apoptosis. Electron microscopic analysis revealed presence of cells with morphological signs of degeneration in a frequency even higher than that found by in situ nick translation. Some of these cells had a characteristic apoptotic appearance with condensed chromatin and cytoplasm, but the large majority of the cells had an ultrastructure typical for cells undergoing cell death by oncosis with membrane disruption and swollen, disintegrating organelles. Thus, although apoptosis clearly takes place in atherosclerotic plaques, oncosis appears to be a much more common mechanism for cell death.
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              • Record: found
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              • Article: found

              Cyclosporine Induces Apoptosis of Mouse Terminal Proximal Straight Tubule Cells

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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                1999
                1999
                10 February 1999
                : 81
                : 2
                : 234-238
                Affiliations
                aDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka-shi, Tokyo and bDivision of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan
                Article
                45282 Nephron 1999;81:234–238
                10.1159/000045282
                9933761
                © 1999 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: 3, Tables: 1, References: 25, Pages: 5
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/45282
                Categories
                Original Paper

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