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      Activation of Peroxisome Proliferator-Activated Receptor-g Inhibits Apoptosis Induced by Serum Deprivation in LLC-PK1 Cells

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          Abstract

          Peroxisome proliferator-activated receptor-γ (PPARγ) belongs to a superfamily of nuclear receptors, which plays important roles in lipid and glucose metabolism. However, expression of PPARγ in extra-adipose tissues and stimulation of apoptosis by PPARγ activators has been previously reported. We investigated the functions of PPARγ using a clonal kidney cell line (LLC-PK1). RT-PCR revealed the expression of PPARγ in LLC-PK1 cells. The cells accumulated fat droplets and increased β-oxidation of free fatty acids in response to troglitazone, a ligand for PPARγ. At physiological concentrations, ligands for PPARγ including troglitazone, BRL49653, and 15-deoxy-δ-12,14-prostaglandin J<sub>2</sub> inhibited serum-deprivation-induced apoptosis of the cells. On the other hand, PPARα activators did not inhibit the apoptosis. Apoptosis of LLC-PK1 cells was determined by a cell viability assay, condensation of the nucleus on fluorescent and electron microscopy, and DNA fragmentation as indicated by the appearance of nucleosomal ladders on an agarose gel. Troglitazone also suppressed serum-deprivation-induced activation of Caspase 3. However, troglitazone did not suppress apoptosis induced by ATP deprivation. Anti-apoptotic effects of troglitazone were partially blocked by a phosphatidylinositol-3-kinase (PI3K) inhibitor, wortmannin, but not by other kinase inhibitors such as PD98059 and AG490. These results suggest that PPARγ is functionally expressed in LLC-PK1 cells, and its activation inhibits apoptosis induced by serum deprivation, at least in part, through the PI3K pathway.

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          Most cited references 8

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          PI3K: Downstream AKTion Blocks Apoptosis

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            Fatty acid-induced   cell apoptosis: A link between obesity and diabetes

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              Direct Regulation of the Akt Proto-Oncogene Product by Phosphatidylinositol-3,4-bisphosphate

               T Franke (1997)
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                Author and article information

                Journal
                EXN
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2002
                2002
                09 October 2002
                : 10
                : 5-6
                : 393-401
                Affiliations
                Third Department of Internal Medicine, Yamanashi Medical University, Tamaho, Yamanashi, Japan
                Article
                65303 Exp Nephrol 2002;10:393–401
                10.1159/000065303
                12381924
                © 2002 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: 8, Tables: 1, References: 39, Pages: 9
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/65303
                Categories
                Original Paper

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