Saquinavir Induced Suicidal Death of Human Erythrocytes
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-11-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/438558 |
| _version_ | 1819150279866580992 |
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| author | Sabrina Waibel Rosi Bissinger Ghada Bouguerra Salem Abbès Florian Lang |
| author_facet | Sabrina Waibel Rosi Bissinger Ghada Bouguerra Salem Abbès Florian Lang |
| author_sort | Sabrina Waibel |
| collection | DOAJ |
| description | 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 µg/ml), significantly increased the percentage of annexin-V-binding cells (≥ 10 µg/ml), significantly increased Fluo3-fluorescence (15 µg/ml), significantly increased DCFDA fluorescence (15 µg/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. |
| first_indexed | 2024-12-22T14:14:59Z |
| format | Article |
| id | doaj.art-3361f12f173a45b49045a7d93c5a6449 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-22T14:14:59Z |
| publishDate | 2015-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-3361f12f173a45b49045a7d93c5a64492022-12-21T18:23:08ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-11-013751973198210.1159/000438558438558Saquinavir Induced Suicidal Death of Human ErythrocytesSabrina WaibelRosi BissingerGhada BouguerraSalem AbbèsFlorian LangBackground/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 µg/ml), significantly increased the percentage of annexin-V-binding cells (≥ 10 µg/ml), significantly increased Fluo3-fluorescence (15 µg/ml), significantly increased DCFDA fluorescence (15 µg/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.http://www.karger.com/Article/FullText/438558PhosphatidylserineCell volumeEryptosisOxidative stressCalcium |
| spellingShingle | Sabrina Waibel Rosi Bissinger Ghada Bouguerra Salem Abbès Florian Lang Saquinavir Induced Suicidal Death of Human Erythrocytes Cellular Physiology and Biochemistry Phosphatidylserine Cell volume Eryptosis Oxidative stress Calcium |
| title | Saquinavir Induced Suicidal Death of Human Erythrocytes |
| title_full | Saquinavir Induced Suicidal Death of Human Erythrocytes |
| title_fullStr | Saquinavir Induced Suicidal Death of Human Erythrocytes |
| title_full_unstemmed | Saquinavir Induced Suicidal Death of Human Erythrocytes |
| title_short | Saquinavir Induced Suicidal Death of Human Erythrocytes |
| title_sort | saquinavir induced suicidal death of human erythrocytes |
| topic | Phosphatidylserine Cell volume Eryptosis Oxidative stress Calcium |
| url | http://www.karger.com/Article/FullText/438558 |
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