Triggering of Erythrocyte Death by Triparanol
The cholesterol synthesis inhibitor Triparanol has been shown to trigger apoptosis in several malignancies. Similar to the apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine transloca...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-08-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/7/8/3359 |
| _version_ | 1811186044607922176 |
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| author | Arbace Officioso Caterina Manna Kousi Alzoubi Florian Lang |
| author_facet | Arbace Officioso Caterina Manna Kousi Alzoubi Florian Lang |
| author_sort | Arbace Officioso |
| collection | DOAJ |
| description | The cholesterol synthesis inhibitor Triparanol has been shown to trigger apoptosis in several malignancies. Similar to the apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress which may activate erythrocytic Ca2+ permeable unselective cation channels with subsequent Ca2+ entry and increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored whether and how Triparanol induces eryptosis. To this end, phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ROS formation from 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) dependent fluorescence. As a result, a 48 h exposure of human erythrocytes to Triparanol (20 µM) significantly increased DCFDA fluorescence and significantly increased Fluo3-fluorescence. Triparanol (15 µM) significantly increased the percentage of annexin-V-binding cells, and significantly decreased the forward scatter. The effect of Triparanol on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. In conclusion, Triparanol leads to eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane. Triparanol is at least in part effective by stimulating ROS formation and Ca2+ entry. |
| first_indexed | 2024-04-11T13:40:31Z |
| format | Article |
| id | doaj.art-4661f167c1874dd49cd56fb059933bd0 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T13:40:31Z |
| publishDate | 2015-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-4661f167c1874dd49cd56fb059933bd02022-12-22T04:21:16ZengMDPI AGToxins2072-66512015-08-01783359337110.3390/toxins7083359toxins7083359Triggering of Erythrocyte Death by TriparanolArbace Officioso0Caterina Manna1Kousi Alzoubi2Florian Lang3Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tuebingen, GermanyDepartment of Biochemistry, Biophysics and General Pathology, School of Medicine and Surgery, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, ItalyDepartment of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tuebingen, GermanyDepartment of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tuebingen, GermanyThe cholesterol synthesis inhibitor Triparanol has been shown to trigger apoptosis in several malignancies. Similar to the apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress which may activate erythrocytic Ca2+ permeable unselective cation channels with subsequent Ca2+ entry and increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored whether and how Triparanol induces eryptosis. To this end, phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ROS formation from 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) dependent fluorescence. As a result, a 48 h exposure of human erythrocytes to Triparanol (20 µM) significantly increased DCFDA fluorescence and significantly increased Fluo3-fluorescence. Triparanol (15 µM) significantly increased the percentage of annexin-V-binding cells, and significantly decreased the forward scatter. The effect of Triparanol on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. In conclusion, Triparanol leads to eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane. Triparanol is at least in part effective by stimulating ROS formation and Ca2+ entry.http://www.mdpi.com/2072-6651/7/8/3359phosphatidylserinecell volumeeryptosisoxidative stresscalcium |
| spellingShingle | Arbace Officioso Caterina Manna Kousi Alzoubi Florian Lang Triggering of Erythrocyte Death by Triparanol Toxins phosphatidylserine cell volume eryptosis oxidative stress calcium |
| title | Triggering of Erythrocyte Death by Triparanol |
| title_full | Triggering of Erythrocyte Death by Triparanol |
| title_fullStr | Triggering of Erythrocyte Death by Triparanol |
| title_full_unstemmed | Triggering of Erythrocyte Death by Triparanol |
| title_short | Triggering of Erythrocyte Death by Triparanol |
| title_sort | triggering of erythrocyte death by triparanol |
| topic | phosphatidylserine cell volume eryptosis oxidative stress calcium |
| url | http://www.mdpi.com/2072-6651/7/8/3359 |
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