Lupescu Adrian, Jilani Kashif, Zbidah Mohanad, Lang Florian
Department of Physiology, University of Tuebingen, Tuebingen, Germany.
Cell Physiol Biochem. 2013;32(2):291-9. doi: 10.1159/000354437. Epub 2013 Jul 31.
Patulin, the most common mycotoxin in apples and apple-derived products, triggers apoptosis and has thus been considered for the treatment of cancer. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling leading to phosphatidylserine-exposure at the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). The present study explored, whether exposure of human erythrocytes to patulin is followed by eryptosis.
Forward scatter was measured to estimate cell volume, annexin V binding to detect phosphatidylserine-exposure, hemoglobin release to quantify hemolysis, and Fluo3-fuorescence to determine [Ca(2+)]i.
A 48 h exposure to patulin significantly increased [Ca(2+)]I (5 µM), significantly decreased forward scatter (5 µM) and significantly increased annexin-V-binding (2.5 µM). Patulin (10 µM) induced annexin-V-binding was virtually abrogated by removal of extracellular Ca(2+).
Patulin stimulates Ca(2+) entry into erythrocytes, an effect triggering suicidal erythrocyte death or eryptosis.
展青霉素是苹果及其衍生产品中最常见的霉菌毒素,可引发细胞凋亡,因此被考虑用于癌症治疗。与有核细胞的凋亡类似,红细胞可能进入自杀性死亡或红细胞凋亡,其特征为细胞萎缩和细胞膜磷脂酰丝氨酸外翻,导致红细胞表面暴露磷脂酰丝氨酸。红细胞凋亡的刺激因素包括胞质Ca(2+)活性([Ca(2+)]i)增加。本研究探讨了人红细胞暴露于展青霉素后是否会发生红细胞凋亡。
通过测量前向散射来估计细胞体积,用膜联蛋白V结合检测磷脂酰丝氨酸暴露,血红蛋白释放定量溶血,用Fluo3荧光测定[Ca(2+)]i。
展青霉素48小时暴露显著增加[Ca(2+)]i(5μM),显著降低前向散射(5μM),并显著增加膜联蛋白V结合(2.5μM)。去除细胞外Ca(2+)后,展青霉素(10μM)诱导的膜联蛋白V结合几乎被消除。
展青霉素刺激Ca(2+)进入红细胞,这种作用引发红细胞自杀性死亡或红细胞凋亡。