Oxidant Preconditioning Protects Human Proximal Tubular Cells against Lethal Oxidant Injury via p38 MAPK and Heme Oxygenase-1

Abstract

Ischemic preconditioning protects the kidney from subsequent ischemic injury but the signal transduction pathways involved are unknown. Human proximal tubular (HK-2) cells were protected from injury with 2.5 m M H₂O₂ by preconditioning with a single 15-min exposure to 500 µ M H₂O₂ followed by 16 h of recovery (oxidant preconditioning). To identify the signaling pathways involved in oxidant preconditioning, we utilized inhibitors of several signaling intermediates (MAPK/ERK kinase I, p38 mitogen-activated protein kinase (MAPK), protein kinase C and tyrosine kinase). A rapid but transient increase in p38 MAPK was observed following oxidant preconditioning and an inhibitor of p38 MAPK (SB203580) abolished the protection provided by oxidant preconditioning. Oxidant preconditioning was also associated with heat shock protein-27 phosphorylation (by p38 MAPK) and an increased synthesis of heme oxygenease-1 (HO-1). Stimulation or inhibition of HO-1 with hemin or Zn(II) protoporphyrin IX, respectively, mimicked or abolished oxidant preconditioning-mediated cytoprotection. Inhibitors of new protein synthesis (cycloheximide) and gene transcription (actinomycin D) also blocked the cytoprotection by oxidant preconditioning. We conclude that oxidant preconditioning protects HK-2 cells against more severe oxidant injury via activation of signaling pathways that include p38 MAPK and increased synthesis of HO-1.

Journal

Journal ID (publisher-id): AJN

Journal ID (nlm-ta): Am J Nephrol

Journal ID (doi): 10.1159/issn.0250-8095

Title: American Journal of Nephrology

Publisher: S. Karger AG

ISSN (Print): 0250-8095

ISSN (Electronic): 1421-9670

Publication date Subscription-year: 2003

Publication date (Print): October 2003

Publication date (Electronic): 08 September 2003

Volume: 23

Issue: 5

Pages: 324-333

Affiliations

Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, N.Y., USA

Article

Publisher ID: 72914 Other ID: Am J Nephrol 2003;23:324–333

DOI: 10.1159/000072914

PubMed ID: 12915776

Copyright statement: © 2003 S. Karger AG, Basel

License:

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: 8, Tables: 1, References: 36, Pages: 10

Product

Self URI (application/pdf): https://www.karger.com/Article/Pdf/72914

Self URI (text/html): https://www.karger.com/Article/FullText/72914

Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology

Categories

Subject: Original Article: Laboratory Investigation