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      Lens Fibre Cell Differentiation – A Link with Apoptosis?

      Ophthalmic Research

      S. Karger AG

      Apoptosis, Programmed cell death, Lens fibre cell differentiation, Denucleation

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          Abstract

          During the process of terminal differentiation, the fibre cells in the eye lens undergo many changes that are reminiscent of apoptotic/necrotic changes. Mitochondria, for instance, undergo permeability transition and nuclear degradation is accompanied by chromatin condensation, disintegration of the nucleolus, dissolution of the nuclear lamina, nuclear pore clustering and fragmentation of the DNA into oligonucleosomal fragments. As during apoptosis, members of the caspase family of proteases were shown to be active during fibre cell differentiation and Bcl-2 overexpression was demonstrated to block normal differentiation of lens cells. In this review, the current knowledge of the sequence of events during cell death is summarised and contrasted with events during lens fibre cell differentiation. Due to the numerous similarities between these processes, lens fibre cell differentiation is suggested to represent an attenuated form of cell death.

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          Most cited references 38

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          Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.

          Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
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            Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis.

            The protease responsible for the cleavage of poly(ADP-ribose) polymerase and necessary for apoptosis has been purified and characterized. This enzyme, named apopain, is composed of two subunits of relative molecular mass (M(r)) 17K and 12K that are derived from a common proenzyme identified as CPP32. This proenzyme is related to interleukin-1 beta-converting enzyme (ICE) and CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans. A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death.
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              Caspases: intracellular signaling by proteolysis.

               V M Dixit,  G Salvesen (1997)
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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                1999
                June 1999
                30 April 1999
                : 31
                : 3
                : 163-183
                Affiliations
                Department of Biochemistry, Medical Sciences Institute, University of Dundee, UK
                Article
                55530 Ophthalmic Res 1999;31:163–183
                10.1159/000055530
                10224500
                © 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: 2, Tables: 2, References: 149, Pages: 21
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