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      Caspase-7, Fas and FasL in Long-Term Renal Ischaemia/Reperfusion and Immunosuppressive Injuries in Rats

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          Abstract

          Background/Aims: Ischaemia/reperfusion (I/R) injury is important in kidney transplantation. We have previously demonstrated that long-term I/R injury and immunosuppression affect apoptosis and inflammation, but the underlying mechanisms are far from clear. In this study, the involvement of caspase-7, Fas and FasL was further investigated. Methods: The right renal pedicle was clamped for 45 min followed by left nephrectomy in 40 rats. Cyclosporine (CsA), tacrolimus (Tac), rapamycin (Rap) or mycophenolate mofetil (MMF) were administered daily for 16 weeks. Caspase-7, Fas and FasL expression, and their correlations with caspase-3, apoptosis, inflammation, renal structure and function were evaluated. Results: Active caspase-7 was significantly increased in I/R and CsA-treated kidneys and decreased by Tac, Rap and MMF, while the caspase-7 precursor was enhanced by Rap. Active caspase-7-stained cells were scattered throughout the tubulointerstitium and often had apoptotic features. Fas, but not FasL, was increased in I/R and CsA-treated kidneys and decreased by Rap and MMF. Fas and FasL proteins were mainly located in dilated tubules. There were close correlations among caspase-7, Fas, caspase-3, apoptosis, inflammation, renal structure and function. Conclusion: Caspase-7, associated with caspase-3, apoptosis and inflammation, might be involved in long-term I/R and immunosuppressive injury, at least in part through the Fas-signalling pathway.

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          Author and article information

          Journal
          AJN
          Am J Nephrol
          10.1159/issn.0250-8095
          American Journal of Nephrology
          S. Karger AG
          0250-8095
          1421-9670
          2007
          July 2007
          26 June 2007
          : 27
          : 4
          : 397-408
          Affiliations
          aDepartment of Infection, Immunity and Inflammation, bDepartment of Cancer Studies and Molecular Medicine and cDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK
          Article
          104741 Am J Nephrol 2007;27:397–408
          10.1159/000104741
          17596683
          30adf956-d7d7-4ce1-8969-6abad8d404d1
          © 2007 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.

          History
          : 21 February 2007
          : 14 May 2007
          Page count
          Figures: 4, Tables: 1, References: 33, Pages: 12
          Categories
          Original Report: Laboratory Investigation

          Cardiovascular Medicine,Nephrology
          Ischaemia/reperfusion injury,Immunosuppression,Caspase-7,Fas,FasL,Apoptosis,Inflammation

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