Journal Mobile Options
Table of Contents
Vol. 18, No. 4-5, 2006
Issue release date: 2006
Cell Physiol Biochem 2006;18:223–232
(DOI:10.1159/000097669)

Stimulation of Suicidal Erythrocyte Death by Methylglyoxal

Nicolay J.P.1 · Schneider J.1 · Niemoeller O.M.1 · Artunc F.1 · Portero-Otin M.2 · Haik Jr. G.3 · Thornalley P.J.2 · Schleicher E.4 · Wieder T.1 · Lang F.1
1Department of Physiology, and 4Department of Internal Medicine, University of Tübingen, 2Department of Biological Sciences, University of Essex, 3George Haik Eye Clinic, New Orleans, Louisiana
email Corresponding Author

Abstract

Diabetes increases the percentage of circulating erythrocytes exposing phosphatidylserine (PS) at the cell surface. PS-exposing erythrocytes are recognized, bound, engulfed and degraded by macrophages. Thus, PS exposure, a feature of suicidal erythrocyte death or eryptosis, accelerates clearance of affected erythrocytes from circulating blood. Moreover, PS-exposing erythrocytes bind to the vascular wall thus interfering with microcirculation. The present study explored mechanisms involved in the triggering of PS exposure by methylgloxal, an extra- and intracellular metabolite which is enhanced in diabetes. PS exposure, cell size and cytosolic Ca2+-activity after methylglyoxal treatment were measured by FACS analysis of annexin V binding, forward scatter and Fluo-3-fluorescence, respectively, and it was shown that the treatment significantly enhanced the percentage of PS-exposing erythrocytes at concentrations (0.3 µM) encountered in diabetic patients. Surprisingly, methylglyoxal did not significantly increase cytosolic Ca2+ concentration, and at concentrations up to 3 µM, did not decrease the forward scatter. Instead, exposure to methylglyoxal inhibited glycolysis thus decreasing ATP and GSH concentrations. In conclusion, methylglyoxal impairs energy production and anti-oxidative defense, effects contributing to the enhanced PS exposure of circulating erythrocytes and eventually resulting in anemia and deranged microcirculation.


 Outline


 goto top of outline Abstract

Diabetes increases the percentage of circulating erythrocytes exposing phosphatidylserine (PS) at the cell surface. PS-exposing erythrocytes are recognized, bound, engulfed and degraded by macrophages. Thus, PS exposure, a feature of suicidal erythrocyte death or eryptosis, accelerates clearance of affected erythrocytes from circulating blood. Moreover, PS-exposing erythrocytes bind to the vascular wall thus interfering with microcirculation. The present study explored mechanisms involved in the triggering of PS exposure by methylgloxal, an extra- and intracellular metabolite which is enhanced in diabetes. PS exposure, cell size and cytosolic Ca2+-activity after methylglyoxal treatment were measured by FACS analysis of annexin V binding, forward scatter and Fluo-3-fluorescence, respectively, and it was shown that the treatment significantly enhanced the percentage of PS-exposing erythrocytes at concentrations (0.3 μM) encountered in diabetic patients. Surprisingly, methylglyoxal did not significantly increase cytosolic Ca2+ concentration, and at concentrations up to 3 μM, did not decrease the forward scatter. Instead, exposure to methylglyoxal inhibited glycolysis thus decreasing ATP and GSH concentrations. In conclusion, methylglyoxal impairs energy production and anti-oxidative defense, effects contributing to the enhanced PS exposure of circulating erythrocytes and eventually resulting in anemia and deranged microcirculation.

Copyright © 2006 S. Karger AG, Basel


goto top of outline 


 goto top of outline Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut der Universität Tübingen
Gmelinstr. 5, D-72076 Tübingen (Germany)
Tel. +49 7071 29 72194, Fax: +49 7071 29 5618
E-Mail florian.lang@uni-tuebingen.de


 goto top of outline Article Information

Accepted: July 27, 2006
Number of Print Pages : 10


 goto top of outline Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 18, No. 4-5, Year 2006 (Cover Date: 2006)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (print), 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


Copyright / Drug Dosage / Disclaimer

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.

Abstract

Diabetes increases the percentage of circulating erythrocytes exposing phosphatidylserine (PS) at the cell surface. PS-exposing erythrocytes are recognized, bound, engulfed and degraded by macrophages. Thus, PS exposure, a feature of suicidal erythrocyte death or eryptosis, accelerates clearance of affected erythrocytes from circulating blood. Moreover, PS-exposing erythrocytes bind to the vascular wall thus interfering with microcirculation. The present study explored mechanisms involved in the triggering of PS exposure by methylgloxal, an extra- and intracellular metabolite which is enhanced in diabetes. PS exposure, cell size and cytosolic Ca2+-activity after methylglyoxal treatment were measured by FACS analysis of annexin V binding, forward scatter and Fluo-3-fluorescence, respectively, and it was shown that the treatment significantly enhanced the percentage of PS-exposing erythrocytes at concentrations (0.3 µM) encountered in diabetic patients. Surprisingly, methylglyoxal did not significantly increase cytosolic Ca2+ concentration, and at concentrations up to 3 µM, did not decrease the forward scatter. Instead, exposure to methylglyoxal inhibited glycolysis thus decreasing ATP and GSH concentrations. In conclusion, methylglyoxal impairs energy production and anti-oxidative defense, effects contributing to the enhanced PS exposure of circulating erythrocytes and eventually resulting in anemia and deranged microcirculation.



 goto top of outline Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut der Universität Tübingen
Gmelinstr. 5, D-72076 Tübingen (Germany)
Tel. +49 7071 29 72194, Fax: +49 7071 29 5618
E-Mail florian.lang@uni-tuebingen.de


 goto top of outline Article Information

Accepted: July 27, 2006
Number of Print Pages : 10


 goto top of outline Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 18, No. 4-5, Year 2006 (Cover Date: 2006)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (print), 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


Copyright / Drug Dosage

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.