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      Caspase-9 Takes Part in Programmed Cell Death in Developing Mouse Kidney

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          Abstract

          Programmed cell death is a mechanism by which organisms dispose of unwanted cells, and it is thought to be an important process in organogenesis. We have already reported the role of caspase-3 in the developing metanephros. While caspase-3 is thought to be positioned downstream of the caspase-activating cascade, the upstream caspase for programmed cell death in the developing kidney is still unknown. In an attempt to identify it, we blocked caspase activity in metanephric explants with caspase inhibitors. Administration of a caspase-9 inhibitor (Ac-IETD-CHO) effectively prevented both ureteric bud branching and nephrogenesis, the same as a caspase-3 inhibitor (Ac-DEVD-CHO). On the other hand, administration of a caspase-8 inhibitor (Ac-LETD-CHO) did not inhibit ureteric bud branching or nephrogenesis. Apaf-1, which executes programmed cell death in the caspase-9-related pathway, was detected in the cells exhibiting caspase-9 activity, and our results suggest that Apaaf-1/caspase-9 activates caspase-3 in kidney organogenesis.

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          Most cited references 15

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          Programmed cell death in animal development.

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            Apoptosis in development.

            Essential to the construction, maintenance and repair of tissues is the ability to induce suicide of supernumerary, misplaced or damaged cells with high specificity and efficiency. Study of three principal organisms--the nematode, fruitfly and mouse--indicate that cell suicide is implemented through the activation of an evolutionarily conserved molecular programme intrinsic to all metazoan cells. Dysfunctions in the regulation or execution of cell suicide are implicated in a wide range of developmental abnormalities and diseases.
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              Longevity in Caenorhabditis elegans reduced by mating but not gamete production.

              Theories of life-history evolution propose that trade-offs occur between fitness components, including longevity and maximal reproduction. In Drosophila, female lifespan is shortened by increased egg production, receipt of male accessory fluid and courting. Male lifespan is also reduced by courting and/or mating. Here we show that in the nematode Caenorhabditis elegans, mating with males reduces the lifespan of hermaphrodites by a mechanism independent of egg production or receipt of sperm. Conversely, males appear unaffected by mating. Thus, in C. elegans there is no apparent trade-off between longevity and increased egg or sperm production, but there is a substantial cost to hermaphrodites associated with copulation.
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                Author and article information

                Journal
                NEE
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2003
                March 2003
                17 November 2004
                : 93
                : 3
                : e117-e124
                Affiliations
                aDepartment of Internal Medicine, Keio University School of Medicine, Tokyo; bBioarchitect Research Group, Cellular and Molecular Biology Laboratory, RIKEN (Institute of Physical and Chemical Research), Saitama, Japan
                Article
                69552 Nephron Exp Nephrol 2003;93:e117–e124
                10.1159/000069552
                12660414
                © 2003 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: 40, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/69552
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Nephrogenesis, Apoptosis, Metanephros, Caspase

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