Age Sensitivity of NFκB Abundance and Programmed Cell Death in Erythrocytes Induced by NFκB Inhibitors

Age Sensitivity of NFκB Abundance and Programmed Cell Death in Erythrocytes Induced by NFκB Inhibitors

Background/Aims: Erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte outer membrane. Susceptibility to eryptosis is enhanced in aged erythrocytes and stimulated by NFκB-inhibitors Bay 11-7082 and parthenolide....

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Bibliographic Details
Main Authors: Mehrdad Ghashghaeinia, Judith C. Cluitmans, Mahmoud Toulany, Mohammad Saki, Martin Köberle, Elisabeth Lang, Peter Dreischer, Tilo Biedermann, Michael Duszenko, Florian Lang, Giel J. Bosman, Thomas Wieder
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2013-09-01
Series:Cellular Physiology and Biochemistry
Subjects:
Cell volume
Eryptosis
Phosphatidylserine
Bay 11-7082
Parthenolide
Online Access:http://www.karger.com/Article/FullText/354481
Description
Summary:Background/Aims: Erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte outer membrane. Susceptibility to eryptosis is enhanced in aged erythrocytes and stimulated by NFκB-inhibitors Bay 11-7082 and parthenolide. Here we explored whether expression of NFκB and susceptibility to inhibitor-induced eryptosis is sensitive to erythrocyte age. Methods: Human erythrocytes were separated into five fractions, based on age-associated characteristics cell density and volume. NFκB compared to ß-actin protein abundance was estimated by Western blotting and cell volume from forward scatter. Phosphatidylserine exposure was identified using annexin-V binding. Results: NFκB was most abundant in young erythrocytes but virtually absent in aged erythrocytes. A 24h or 48h exposure to Ringer resulted in spontaneous decrease of forward scatter and increase of annexin V binding, effects more pronounced in aged than in young erythrocytes. Both, Bay 11-7082 (20 µM) and parthenolide (100 µM) triggered eryptosis, effects again most pronounced in aged erythrocytes. Conclusion: NFκB protein abundance is lowest and spontaneous eryptosis as well as susceptibility to Bay 11-7082 and parthenolide highest in aged erythrocytes. Thus, inhibition of NFκB signalling alone is not responsible for the stimulation of eryptosis by parthenolide or Bay 11-7082.
ISSN:1015-8987
1421-9778

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