| Potential roles of the NFκB and glutathione pathways in mature human erythrocytes. | |
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MedLine Citation:
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PMID: 22105338 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Anucleated erythrocytes were long considered as oxygen-transporting cells with limited regulatory functions. Components of different nuclear signaling pathways have not been investigated in those cells, yet. Surprisingly, we repeatedly found significant amounts of transcription factors in purified erythrocyte preparations, i.e. nuclear factor κB (NFκB), and major components of the canonical NFκB signaling pathway. To investigate the functional role of NFκB signaling, the effects of the preclinical compounds Bay 11-7082 and parthenolide on the survival of highly purified erythrocytes were investigated. Interestingly, both inhibitors of the NFκB pathway triggered erythrocyte programmed cell death as demonstrated by enhanced phospholipid scrambling (phosphatidylserine exposure) and cell shrinkage. Anucleated erythrocytes are an ideal cellular model allowing the study of nongenomic mechanisms contributing to suicidal cell death. As NFκB inhibitors might also interfere with the anti-oxidative defense systems of the cell, we measured the levels of reduced glutathione (GSH) after challenge with the inhibitors. Indeed, incubation of erythrocytes with Bay 11-7082 clearly decreased erythrocyte GSH levels. In conclusion, the pharmacological inhibitors of the NFκB pathway Bay 11-7082 and parthenolide interfere with the survival of erythrocytes involving mechanisms other than disruption of NFκB-dependent gene expression. Besides affecting erythrocyte survival, NFκB inhibition and induction of erythrocyte phosphatidylserine exposure may influence blood clotting. Future studies will be aimed at discriminating between NFκB-dependent and NFκB-independent GSH-mediated effects of Bay 11-7082 and parthenolide on erythrocyte death. |
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Authors:
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Mehrdad Ghashghaeinia; Mahmoud Toulany; Mohammad Saki; H Peter Rodemann; Ulrich Mrowietz; Florian Lang; Thomas Wieder |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-21 |
Journal Detail:
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Title: Cellular & molecular biology letters Volume: - ISSN: 1689-1392 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9607427 Medline TA: Cell Mol Biol Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Physiology, Eberhard Karls University Tübingen, Gmelinstr. 5, D-72076, Tübingen, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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