+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Heparin Increases Protein S Levels in Cultured Endothelial Cells by Causing a Block in Degradation


      Journal of Vascular Research

      S. Karger AG

      Protein S, Heparin, Endothelial cells

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Heparin is a natural anticoagulant molecule that can alter the activity and/or levels of other molecules involved in blood coagulation. Protein S, an anticoagulant protein, is synthesized and released into the plasma by endothelial cells. Immunological assays revealed a significant increase in protein S found in the media and in the endothelial cells after heparin treatment. Time assays revealed a rapid heparin effect on protein S levels in the media. Upon treatment with chondroitin sulfate, a small increase in the amount of protein S in the conditioned medium was also detected but the change in the cell-associated protein S levels after chondroitin sulfate treatment was a decrease rather than the increase implying that heparin and chondroitin sulfate are operating through different mechanisms. Radioimmunoprecipitations and cycloheximide treatments indicated no significant difference in protein S synthesis in heparin treated cells. In experiments comparing heparin and ammonium chloride effects, heparin seems to mimic the ammonium chloride effect on the levels of protein S in the media. Together, the data indicate that heparin increases the levels of protein S found in the media of cultured endothelial cells by producing a specific block in protein S degradation.

          Related collections

          Most cited references 2

          • Record: found
          • Abstract: not found
          • Article: not found

          Mechanisms of intracellular protein breakdown.

            • Record: found
            • Abstract: found
            • Article: not found

            Trans-repressor activity of nuclear glycosaminoglycans on Fos and Jun/AP-1 oncoprotein-mediated transcription

            Heparin blocks the phorbol ester-induced progression of nontransformed cells through the G0/G1 phase (Wright, T.C., L.A. Pukac, J.J. Castellot, M.J. Karnovsky, R.A. Levine, H.-Y. Kim-Park, and J. Campisi. 1989. Proc. Natl. Acad. Sci. USA. 86: 3199-3203) or G1 to S phase (Reilly, C. F., M. S. Kindy, K. E. Brown, R. D. Rosenberg, and G. E Sonenshein. 1989. J. Biol. Chem. 264:6990-6995) of the cell cycle. Cell cycle arrest was associated with decreased levels of stage-specific mRNAs suggesting transcriptional regulation of cell growth. In the present report, we show that heparin selectively repressed TPA- inducible AP-1-mediated gene expression. Heparin-induced trans- repression was observed in primary vascular smooth muscle cells, as well as in the transformed HeLa cell line and in nondifferentiated F9 teratocarcinoma cells. Inhibition of AP-1-mediated trans-activation occurred with heparin and pentosan polysulfate but not with chondroitin sulfate A or C. Heparin-binding peptides or heparitinase I addition to nuclear lysates of heparin-treated cells allowed enhanced recovery of endogenous AP-1-specific DNA binding activity. We propose a model in which nuclear glycosaminoglycans play a trans-regulatory role in altering the patterns of inducible gene expression.

              Author and article information

              J Vasc Res
              Journal of Vascular Research
              S. Karger AG
              December 1998
              23 September 2008
              : 35
              : 6
              : 437-448
              Department of Biological Sciences, Lehigh University, Bethlehem, Pa., USA
              25615 J Vasc Res 1998;35:437–448
              © 1998 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: 9, Tables: 1, References: 41, Pages: 12
              Research Paper


              Comment on this article