Stimulation of Suicidal Erythrocyte Death by Phosphatase Inhibitor Calyculin A
Background/Aims: The serine/threonine protein phosphatase 1 and 2a inhibitor Calyculin A may trigger suicidal death or apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2016-11-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/452534 |
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| author | Mustafa Almasry Mohamed Jemaà Morena Mischitelli Caterina Faggio Florian Lang |
| author_facet | Mustafa Almasry Mohamed Jemaà Morena Mischitelli Caterina Faggio Florian Lang |
| author_sort | Mustafa Almasry |
| collection | DOAJ |
| description | Background/Aims: The serine/threonine protein phosphatase 1 and 2a inhibitor Calyculin A may trigger suicidal death or apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+] i). Eryptosis is fostered by activation of staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, and D4476 sensitive casein kinase. Eryptosis may further involve zVAD sensitive caspases. The present study explored, whether Calyculin A induces eryptosis and, if so, whether its effect requires Ca2+ entry, kinases and/or caspases Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, and [Ca2+] i from Fluo-3 fluorescence, as determined by flow cytometry. Results: A 48 hours exposure of human erythrocytes to Calyculin A (≥ 2.5 nM) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter and significantly increased Fluo-3 fluorescence. The effect of Calyculin A on annexin-V-binding was significantly blunted by removal of extracellular Ca2+, by staurosorine (1 µM), SB203580 (2 µM), D4476 (10 µM), and zVAD (10 µM). Conclusions: Calyculin A triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part requiring Ca2+ entry, kinase activity and caspase activation. |
| first_indexed | 2024-04-12T06:02:25Z |
| format | Article |
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| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-12T06:02:25Z |
| publishDate | 2016-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-23b6f6767c2c470db9352730af8dfbf32022-12-22T03:45:00ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-11-01401-216317110.1159/000452534452534Stimulation of Suicidal Erythrocyte Death by Phosphatase Inhibitor Calyculin AMustafa AlmasryMohamed JemaàMorena MischitelliCaterina FaggioFlorian LangBackground/Aims: The serine/threonine protein phosphatase 1 and 2a inhibitor Calyculin A may trigger suicidal death or apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+] i). Eryptosis is fostered by activation of staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, and D4476 sensitive casein kinase. Eryptosis may further involve zVAD sensitive caspases. The present study explored, whether Calyculin A induces eryptosis and, if so, whether its effect requires Ca2+ entry, kinases and/or caspases Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, and [Ca2+] i from Fluo-3 fluorescence, as determined by flow cytometry. Results: A 48 hours exposure of human erythrocytes to Calyculin A (≥ 2.5 nM) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter and significantly increased Fluo-3 fluorescence. The effect of Calyculin A on annexin-V-binding was significantly blunted by removal of extracellular Ca2+, by staurosorine (1 µM), SB203580 (2 µM), D4476 (10 µM), and zVAD (10 µM). Conclusions: Calyculin A triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part requiring Ca2+ entry, kinase activity and caspase activation.http://www.karger.com/Article/FullText/452534PhosphatidylserineCell volumeEryptosisCalcium |
| spellingShingle | Mustafa Almasry Mohamed Jemaà Morena Mischitelli Caterina Faggio Florian Lang Stimulation of Suicidal Erythrocyte Death by Phosphatase Inhibitor Calyculin A Cellular Physiology and Biochemistry Phosphatidylserine Cell volume Eryptosis Calcium |
| title | Stimulation of Suicidal Erythrocyte Death by Phosphatase Inhibitor Calyculin A |
| title_full | Stimulation of Suicidal Erythrocyte Death by Phosphatase Inhibitor Calyculin A |
| title_fullStr | Stimulation of Suicidal Erythrocyte Death by Phosphatase Inhibitor Calyculin A |
| title_full_unstemmed | Stimulation of Suicidal Erythrocyte Death by Phosphatase Inhibitor Calyculin A |
| title_short | Stimulation of Suicidal Erythrocyte Death by Phosphatase Inhibitor Calyculin A |
| title_sort | stimulation of suicidal erythrocyte death by phosphatase inhibitor calyculin a |
| topic | Phosphatidylserine Cell volume Eryptosis Calcium |
| url | http://www.karger.com/Article/FullText/452534 |
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