Nguyen Tan Thanh, Föller Michael, Lang Florian
Physiologisches Institut der Universitat Tubingen, Tubingen, Germany.
J Appl Toxicol. 2009 Jan;29(1):79-83. doi: 10.1002/jat.1390.
Suicidal erythrocyte death or eryptosis is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure at the erythrocyte surface. Triggers of eryptosis include increase in cytosolic Ca(2+) activity, formation of ceramide and energy depletion. Excessive eryptosis contributes to several anemic conditions. Intoxication with inorganic tin(II) may lead to anemia. The present study therefore explored whether tin influences eryptosis. To this end, erythrocytic phosphatidylserine exposure was estimated from annexin V-binding, cell volume from forward scatter, cytosolic Ca(2+) activity from Fluo3 fluorescence, ceramide formation from binding of fluorescent antibodies and cytosolic ATP utilizing a luciferin-luciferase assay kit. Under control conditions, eryptosis was observed in less than 5% of the erythrocytes. Exposure to tin (1-100 microm) significantly increased the percentage of PS-exposing erythrocytes and decreased cell volume. The effect was paralleled by an increase in the cytosolic Ca(2+) concentration, ceramide formation and a decrease of intracellular ATP concentration. In conclusion, tin triggers eryptosis, an effect at least partially due to Ca(2+ )entry, ceramide formation and ATP depletion. The effect could contribute to tin-induced anemia.
自杀性红细胞死亡或红细胞凋亡的特征是细胞皱缩以及细胞膜磷脂酰丝氨酸（PS）外翻至红细胞表面。红细胞凋亡的触发因素包括胞质Ca(2+)活性增加、神经酰胺形成和能量耗竭。过度的红细胞凋亡会导致多种贫血症状。无机锡（II）中毒可能导致贫血。因此，本研究探讨了锡是否会影响红细胞凋亡。为此，通过膜联蛋白V结合来评估红细胞磷脂酰丝氨酸外翻情况，通过前向散射评估细胞体积，通过Fluo3荧光评估胞质Ca(2+)活性，通过荧光抗体结合评估神经酰胺形成，并使用荧光素-荧光素酶检测试剂盒评估胞质ATP。在对照条件下，观察到不到5%的红细胞发生凋亡。暴露于锡（1 - 100微摩尔）显著增加了磷脂酰丝氨酸外翻的红细胞百分比并减小了细胞体积。这种效应伴随着胞质Ca(2+)浓度增加、神经酰胺形成以及细胞内ATP浓度降低。总之，锡触发红细胞凋亡，这种效应至少部分归因于Ca(2+)内流、神经酰胺形成和ATP耗竭。这种效应可能导致锡诱导的贫血。
