Efavirenz Induced Suicidal Death of Human Erythrocytes
| Autor: | Salem Abbes, Rosi Bissinger, Ghada Bouguerra, Sabrina Waibel, Abdulla Al Mamun Bhuyan, Florian Lang |
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| Přispěvatelé: | Laboratory of Molecular and Cellular Hematology, Laboratoire d'hématologie moléculaire et cellulaire (LR11IPT07), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Department of Physiology, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Physiologisches Institut |
| Rok vydání: | 2015 |
| Předmět: |
Cyclopropanes
Ceramide Programmed cell death Efavirenz Erythrocytes Physiology [SDV]Life Sciences [q-bio] Eryptosis Biology Pharmacology In Vitro Techniques p38 kinase lcsh:Physiology lcsh:Biochemistry chemistry.chemical_compound Annexin Cell volume Extracellular Humans lcsh:QD415-436 Phosphatidylserine lcsh:QP1-981 Cell Death Flow Cytometry 3. Good health Benzoxazines Oxidative Stress chemistry Biochemistry Apoptosis Alkynes Reverse Transcriptase Inhibitors Calcium Casein kinase 1 Casein kinase |
| Zdroj: | Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry, Karger, 2015, 37 (6), pp.2496-2507. ⟨10.1159/000438602⟩ Cellular Physiology and Biochemistry, Vol 37, Iss 6, Pp 2496-2507 (2015) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | International audience; Background/Aims: The reverse transcriptase inhibitor efavirenz utilized for the treatment of human immunodeficiency virus (HIV)-1 infection, triggers suicidal cell death or apoptosis, an effect in part due to interference with mitochondrial potential. Side effects of efavirenz include anemia. Causes of anemia include accelerated clearance of circulating erythrocytes. Even though lacking mitochondria, erythrocytes may enter suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca2+ entry and increase of cytosolic Ca2+ activity ([Ca2+](i)), oxidative stress, ceramide, as well as activation of p38 kinase, casein kinase 1 alpha and/or cyclooxygenase. The present study explored, whether and how efavirenz induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca2+](i) from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence, and ceramide abundance utilizing selective antibodies. Results: A 48 hours exposure of human erythrocytes to efavirenz (>= 2 mu g/ml) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter (2 mu g/ml), significantly increased Fluo3-fluorescence (>= 2 mu g/ml), but did not significantly modify DCFDA fluorescence or ceramide abundance. The effect of efavirenz on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. The effect of efavirenz on annexin-V-binding was further significantly blunted by p38 kinase inhibitor SB203580 (2 mu M) and casein kinase 1 alpha inhibitor D4476 (10 mu M), but not by cyclooxygenase inhibitor aspirin (50 mu M). Conclusions: Efavirenz triggers cell shrinkage and phosphatidylserine translocation to the erythrocyte surface, an effect in part due to stimulation of Ca2+ entry as well as activation of p38 kinase and casein kinase 1 alpha. (C) 2015 The Author(s) Published by S. Karger AG, Basel |
| Databáze: | OpenAIRE |
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