Inhibition of Suicidal Erythrocyte Death by Reversine
Background/Aims: The A3 adenosine receptor antagonist reversine (2-(4-morpholinoanilino)-6-cyclohexylaminopurine) influences cellular differentiation, inhibits cell proliferation, induces cell-cycle arrest, triggers apoptosis, causes cell swelling with polyploidy and stimulates autophagy. The effect...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-04-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/475654 |
| _version_ | 1819206291133825024 |
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| author | Mohamed Jemaà Myriam Fezai Florian Lang |
| author_facet | Mohamed Jemaà Myriam Fezai Florian Lang |
| author_sort | Mohamed Jemaà |
| collection | DOAJ |
| description | Background/Aims: The A3 adenosine receptor antagonist reversine (2-(4-morpholinoanilino)-6-cyclohexylaminopurine) influences cellular differentiation, inhibits cell proliferation, induces cell-cycle arrest, triggers apoptosis, causes cell swelling with polyploidy and stimulates autophagy. The effect on apoptosis involves mitochondria and caspases. Erythrocytes are lacking mitochondria but express caspases and are, similar to apoptosis of nucleated cells, able to enter suicidal erythrocyte death or eryptosis. Stimulators of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), energy depletion and oxidative stress. The present study explored, whether reversine influences eryptosis. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding and cell volume from forward scatter. Measurements were made without or with energy depletion (glucose deprivation for 48 hours), Ca2+ loading (30 minutes treatment with 1 µM Ca2+ ionophore ionomycin), or oxidative stress (15 min exposure to 0.3 mM tert-butylhydroperoxide). Results: A 48 hours exposure of human erythrocytes to reversine (1-10 µM) did not significantly modify the percentage of annexin-V-binding cells and forward scatter. Energy depletion, Ca2+ loading, and oxidative stress were each followed by profound and significant increase of the percentage annexin-V-binding erythrocytes and a significant decrease of forward scatter. The effects of each, Ca2+ loading, energy depletion and oxidative stress on annexin-V-binding were significantly blunted in the presence of reversine (1-10 µM). The effect of ionomycin, but not the effects of energy depletion and oxidative stress on forward scatter were again significantly blunted in the presence of reversine (≥1 µM]. Conclusions: Reversine is a powerful inhibitor of cell membrane scrambling following energy depletion, Ca2+ loading and oxidative stress. |
| first_indexed | 2024-12-23T05:05:16Z |
| format | Article |
| id | doaj.art-1e4a0d44e0774de28b786eb3b16483f5 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-23T05:05:16Z |
| publishDate | 2017-04-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-1e4a0d44e0774de28b786eb3b16483f52022-12-21T17:59:07ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-04-014162363237310.1159/000475654475654Inhibition of Suicidal Erythrocyte Death by ReversineMohamed JemaàMyriam FezaiFlorian LangBackground/Aims: The A3 adenosine receptor antagonist reversine (2-(4-morpholinoanilino)-6-cyclohexylaminopurine) influences cellular differentiation, inhibits cell proliferation, induces cell-cycle arrest, triggers apoptosis, causes cell swelling with polyploidy and stimulates autophagy. The effect on apoptosis involves mitochondria and caspases. Erythrocytes are lacking mitochondria but express caspases and are, similar to apoptosis of nucleated cells, able to enter suicidal erythrocyte death or eryptosis. Stimulators of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), energy depletion and oxidative stress. The present study explored, whether reversine influences eryptosis. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding and cell volume from forward scatter. Measurements were made without or with energy depletion (glucose deprivation for 48 hours), Ca2+ loading (30 minutes treatment with 1 µM Ca2+ ionophore ionomycin), or oxidative stress (15 min exposure to 0.3 mM tert-butylhydroperoxide). Results: A 48 hours exposure of human erythrocytes to reversine (1-10 µM) did not significantly modify the percentage of annexin-V-binding cells and forward scatter. Energy depletion, Ca2+ loading, and oxidative stress were each followed by profound and significant increase of the percentage annexin-V-binding erythrocytes and a significant decrease of forward scatter. The effects of each, Ca2+ loading, energy depletion and oxidative stress on annexin-V-binding were significantly blunted in the presence of reversine (1-10 µM). The effect of ionomycin, but not the effects of energy depletion and oxidative stress on forward scatter were again significantly blunted in the presence of reversine (≥1 µM]. Conclusions: Reversine is a powerful inhibitor of cell membrane scrambling following energy depletion, Ca2+ loading and oxidative stress.http://www.karger.com/Article/FullText/475654PhosphatidylserineEryptosisReversineEnergy depletionOxidative stressCalcium |
| spellingShingle | Mohamed Jemaà Myriam Fezai Florian Lang Inhibition of Suicidal Erythrocyte Death by Reversine Cellular Physiology and Biochemistry Phosphatidylserine Eryptosis Reversine Energy depletion Oxidative stress Calcium |
| title | Inhibition of Suicidal Erythrocyte Death by Reversine |
| title_full | Inhibition of Suicidal Erythrocyte Death by Reversine |
| title_fullStr | Inhibition of Suicidal Erythrocyte Death by Reversine |
| title_full_unstemmed | Inhibition of Suicidal Erythrocyte Death by Reversine |
| title_short | Inhibition of Suicidal Erythrocyte Death by Reversine |
| title_sort | inhibition of suicidal erythrocyte death by reversine |
| topic | Phosphatidylserine Eryptosis Reversine Energy depletion Oxidative stress Calcium |
| url | http://www.karger.com/Article/FullText/475654 |
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