Effect of Thioridazine on Erythrocytes

被引:43
作者
Lang, Elisabeth [1 ]
Modicano, Paola [1 ,2 ]
Arnold, Markus [1 ]
Bissinger, Rosi [1 ]
Faggio, Caterina [2 ]
Abed, Majed [1 ]
Lang, Florian [1 ]
机构
[1] Univ Tubingen, Dept Physiol, D-72076 Tubingen, Germany
[2] Univ Messina, Dept Biol & Environm Sci, I-98166 Agata Messina, Italy
关键词
phosphatidylserine; thioridazine; calcium; cell volume; eryptosis; PROGRAMMED CELL-DEATH; RED-BLOOD-CELLS; SUICIDAL DEATH; APOPTOTIC DEATH; CATION CHANNELS; PHOSPHATIDYLSERINE EXPOSURE; ERYPTOTIC ERYTHROCYTES; INFECTED ERYTHROCYTES; INDUCED ADHESION; CA2+ ENTRY;
D O I
10.3390/toxins5101918
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Background: Thioridazine, a neuroleptic phenothiazine with antimicrobial efficacy is known to trigger anemia. At least in theory, the anemia could result from stimulation of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and by phospholipid scrambling of the cell membrane with phosphatidylserine exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+-concentration ([Ca2+](i)) and activation of p38 kinase. The present study explored, whether thioridazine elicits eryptosis. Methods: [Ca2+](i) has been estimated from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin-V-binding, and hemolysis from hemoglobin release. Results: A 48 hours exposure to thioridazine was followed by a significant increase of [Ca2+](i) (30 mu M), decrease of forward scatter (30 mu M), and increase of annexin-V-binding (12 mu M). Nominal absence of extracellular Ca2+ and p38 kinase inhibitor SB203580 (2 mu M) significantly blunted but did not abolish annexin-V-binding following thioridazine exposure. Conclusions: Thioridazine stimulates eryptosis, an effect in part due to entry of extracellular Ca2+ and activation of p38 kinase.
引用
收藏
页码:1918 / 1931
页数:14
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