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Vol. 26, No. 6, 2010
Issue release date: 2010
Cell Physiol Biochem 2010;26:859–868
(DOI:10.1159/000323995)

Stimulation of Suicidal Erythrocyte Death by α-Lipoic Acid

Bhavsar S.K. · Bobbala D. · Xuan N.T. · FÖller M. · Lang F.
Department of Physiology, University of Tübingen, Tübingen
email Corresponding Author

Abstract

α-lipoic acid, a nutrient with both, antioxidant and oxidant activity induces apoptosis in a variety of cells. Owing to its proapoptotic potency α-lipoic acid has been suggested for the therapy of cancer. α-Lipoic acid stimulates apoptosis by induction of oxidative stress and subsequent activation of caspases. Oxidative stress could similarly trigger caspase activation and suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling and cell shrinkage. Eryptosis is triggered by increase of cytosolic Ca2+ concentration and/or ceramide formation. The present study explored whether α -lipoic acid influences eryptosis. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca2+ concentration from Fluo3 fluorescence, caspase activation and ceramide formation utilizing respective antibodies, cytosolic ATP concentration from a luciferase-assay. Within 48 hours, exposure to α-lipoic acid (10 - 75 mM) significantly decreased forward scatter, increased cytosolic Ca2+ concentration, decreased ATP concentration, activated caspase 3, stimulated formation of ceramide and triggered annexin V-binding. Glucose depletion (48 h) was followed by decrease of forward scatter and increase of annexin V-binding, effects significantly augmented in the presence of α-lipoic acid (20 mM). Oxidative stress (30 min 0.3 mM tert-butylhydroperoxide) similarly triggered annexin binding, an effect slightly but significantly blunted by α-lipoic acid. In conclusion, α-lipoic acid triggers eryptosis but by the same token counteracts eryptosis during oxidative stress. α-lipoic acid sensitive eryptosis may lead to anemia and derangements of microcirculation.


 Outline


 goto top of outline Key Words

  • Phosphatidylserine
  • Scrambling
  • Calcium
  • Cell volume
  • Eryptosis
  • Apoptosis

 goto top of outline Abstract

α-lipoic acid, a nutrient with both, antioxidant and oxidant activity induces apoptosis in a variety of cells. Owing to its proapoptotic potency α-lipoic acid has been suggested for the therapy of cancer. α-Lipoic acid stimulates apoptosis by induction of oxidative stress and subsequent activation of caspases. Oxidative stress could similarly trigger caspase activation and suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling and cell shrinkage. Eryptosis is triggered by increase of cytosolic Ca2+ concentration and/or ceramide formation. The present study explored whether α -lipoic acid influences eryptosis. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca2+ concentration from Fluo3 fluorescence, caspase activation and ceramide formation utilizing respective antibodies, cytosolic ATP concentration from a luciferase-assay. Within 48 hours, exposure to α-lipoic acid (10 - 75 mM) significantly decreased forward scatter, increased cytosolic Ca2+ concentration, decreased ATP concentration, activated caspase 3, stimulated formation of ceramide and triggered annexin V-binding. Glucose depletion (48 h) was followed by decrease of forward scatter and increase of annexin V-binding, effects significantly augmented in the presence of α-lipoic acid (20 mM). Oxidative stress (30 min 0.3 mM tert-butylhydroperoxide) similarly triggered annexin binding, an effect slightly but significantly blunted by α-lipoic acid. In conclusion, α-lipoic acid triggers eryptosis but by the same token counteracts eryptosis during oxidative stress. α-lipoic acid sensitive eryptosis may lead to anemia and derangements of microcirculation.

Copyright © 2010 S. Karger AG, Basel


 goto top of outline Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut, Universität Tübingen
Gmelinstr. 5, 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: October 20, 2010
Published online: January 04, 2011
Number of Print Pages : 10


 goto top of outline Publication Details

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

Vol. 26, No. 6, Year 2010 (Cover Date: 2010)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 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

α-lipoic acid, a nutrient with both, antioxidant and oxidant activity induces apoptosis in a variety of cells. Owing to its proapoptotic potency α-lipoic acid has been suggested for the therapy of cancer. α-Lipoic acid stimulates apoptosis by induction of oxidative stress and subsequent activation of caspases. Oxidative stress could similarly trigger caspase activation and suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling and cell shrinkage. Eryptosis is triggered by increase of cytosolic Ca2+ concentration and/or ceramide formation. The present study explored whether α -lipoic acid influences eryptosis. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca2+ concentration from Fluo3 fluorescence, caspase activation and ceramide formation utilizing respective antibodies, cytosolic ATP concentration from a luciferase-assay. Within 48 hours, exposure to α-lipoic acid (10 - 75 mM) significantly decreased forward scatter, increased cytosolic Ca2+ concentration, decreased ATP concentration, activated caspase 3, stimulated formation of ceramide and triggered annexin V-binding. Glucose depletion (48 h) was followed by decrease of forward scatter and increase of annexin V-binding, effects significantly augmented in the presence of α-lipoic acid (20 mM). Oxidative stress (30 min 0.3 mM tert-butylhydroperoxide) similarly triggered annexin binding, an effect slightly but significantly blunted by α-lipoic acid. In conclusion, α-lipoic acid triggers eryptosis but by the same token counteracts eryptosis during oxidative stress. α-lipoic acid sensitive eryptosis may lead to anemia and derangements of microcirculation.



 goto top of outline Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut, Universität Tübingen
Gmelinstr. 5, 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: October 20, 2010
Published online: January 04, 2011
Number of Print Pages : 10


 goto top of outline Publication Details

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

Vol. 26, No. 6, Year 2010 (Cover Date: 2010)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 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.