Saquinavir Induced Suicidal Death of Human Erythrocytes
| Autor: | Salem Abbes, Sabrina Waibel, Florian Lang, Rosi Bissinger, Ghada Bouguerra |
|---|---|
| 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 |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Ceramide
Erythrocytes Physiology [SDV]Life Sciences [q-bio] Eryptosis Apoptosis Phosphatidylserines Pharmacology Biology Ceramides medicine.disease_cause Hemolysis lcsh:Physiology lcsh:Biochemistry chemistry.chemical_compound Phospholipid scrambling Cell volume medicine Extracellular Humans lcsh:QD415-436 Phosphatidylserine Saquinavir chemistry.chemical_classification Reactive oxygen species Aniline Compounds lcsh:QP1-981 3. Good health Spectrometry Fluorescence Xanthenes Biochemistry chemistry Oxidative stress Calcium Reactive Oxygen Species medicine.drug |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 37, Iss 5, Pp 1973-1982 (2015) Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry, Karger, 2015, 37 (5), pp.1973-1982. ⟨10.1159/000438558⟩ |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | International audience; Background/Aims: The antiretroviral protease inhibitor saquinavir is used for the treatment of HIV infections. Effects of saquinavir include induction of apoptosis, the suicidal death of nucleated cells. Saquinavir treatment may further lead to anemia. In theory, anemia could result from accelerated erythrocyte loss by enhanced suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+](i)), oxidative stress with increase of reactive oxygen species (ROS) and ceramide. The present study explored, whether and how saquinavir induces eryptosis. Methods: To this end, flow cytometry was employed to estimate erythrocyte volume from forward scatter, phosphatidylserine exposure at the cell surface from annexin-V-binding, [Ca2+](i) from Fluo3-fluorescence, ROS abundance from DCFDA fluorescence and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to saquinavir significantly decreased forward scatter (>= 5 mu g/ml), significantly increased the percentage of annexin-V-binding cells (>= 10 mu g/ml), significantly increased Fluo3-fluorescence (15 mu g/ml), significantly increased DCFDA fluorescence (15 mu g/ml), but did not significantly modify ceramide abundance. The effect of saquinavir on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusions: Saquinavir triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of ROS formation and Ca2+ entry. (C) 2015 The Author(s) Published by S. Karger AG, Basel |
| Databáze: | OpenAIRE |
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