Sensitization of Erythrocytes to Suicidal Erythrocyte Death Following Water Deprivation
Background/Aims: Klotho deficiency results in excessive formation of 1,25(OH) 2 D 3 , accelerated ageing and early death. Moreover, klotho deficiency enhances eryptosis, the suicidal erythrocyte death characterized by phosphatidylserine exposure at the erythrocyte surface. Triggers of eryptosis incl...
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Veröffentlicht in: | Kidney & blood pressure research 2013-01, Vol.37 (6), p.567-578 |
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Sprache: | eng |
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Zusammenfassung: | Background/Aims: Klotho deficiency results in excessive formation of 1,25(OH) 2 D 3 , accelerated ageing and early death. Moreover, klotho deficiency enhances eryptosis, the suicidal erythrocyte death characterized by phosphatidylserine exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca 2+ -activity ([Ca 2+ ] i ), glucose depletion, hyperosmotic shock and oxidative stress. Klotho expression is decreased and 1,25(OH) 2 D 3 -formation enhanced by dehydration. The present study thus explored whether dehydration influences eryptosis. Methods: Blood was drawn from hydrated or 36h dehydrated mice. Plasma osmolarity was determined by vapour pressure method, plasma 1,25(OH) 2 D 3 and aldosterone concentrations using ELISA, and plasma Ca 2+ -concentration utilizing photometry. Erythrocytes were exposed to Ca 2+ -ionophore ionomycin (1 µM, 30 min), energy depletion (12 h glucose removal), hyperosmotic shock (500 mM sucrose added, 2 h) and oxidative stress (100 µM tert-butyl-hydroperoxide, 30 min) and phosphatidylserine exposure at the erythrocyte surface estimated from annexin V binding. Results: Dehydration increased plasma osmolarity and plasma 1,25(OH) 2 D 3 and aldosterone concentrations. Dehydration did not significantly modify phosphatidylserine-exposure of freshly drawn erythrocytes but significantly enhanced the increase of phosphatidylserine-exposure under control conditions and following treatment with ionomycin, glucose-deprivation, hyperosmolarity or tert-butyl-hydroperoxide. Conclusions: Dehydration sensitizes the erythrocytes to spontaneous eryptosis and to the triggering of eryptosis by excessive Ca 2+ -entry, energy depletion, hyperosmotic shock and oxidative stress. |
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ISSN: | 1420-4096 1423-0143 |
DOI: | 10.1159/000355737 |