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玉米赤霉烯酮暴露后依赖钙(Ca2+)的自杀性红细胞死亡。

Ca(2+)-dependent suicidal erythrocyte death following zearalenone exposure.

机构信息

Department of Physiology, Physiologisches Institut, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.

出版信息

Arch Toxicol. 2013 Oct;87(10):1821-8. doi: 10.1007/s00204-013-1037-1. Epub 2013 Mar 21.

DOI:10.1007/s00204-013-1037-1
PMID:23515940
Abstract

Zearalenone, a cereal mycotoxin with mycoestrogen activity and effect on fertility, is known to trigger apoptosis of a variety of nucleated cell types including hematopoietic progenitor cells. In analogy to apoptosis of nucleated cells, eryptosis, the suicidal death of erythrocytes, leads to cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. The most important stimulator of eryptosis is an increase in cytosolic Ca(2+) activity ([Ca(2+)]i). The present study explored whether zearalenone triggers eryptosis. Erythrocyte volume was estimated from forward scatter, phosphatidylserine exposure at the erythrocyte surface from annexin-V binding, hemolysis from hemoglobin release, and [Ca(2+)]i from Fluo3 fluorescence. A 48-h exposure to zearalenone (≥25 μM) was followed by a significant increase in [Ca(2+)]i and annexin-V binding, and a significant decrease in forward scatter. The effect on annexin-V binding was significantly blunted in the nominal absence of extracellular Ca(2+). Zearalenone stimulates the suicidal erythrocyte death, an effect at least partially due to stimulation of Ca(2+) entry.

摘要

玉米赤霉烯酮是一种具有类雌激素活性和生殖毒性的谷物真菌毒素,已知它能诱导包括造血祖细胞在内的各种有核细胞类型的凋亡。类似于有核细胞的凋亡,红细胞的细胞自杀死亡即红细胞皱缩,导致细胞膜磷脂酰丝氨酸外翻。细胞内钙离子浓度([Ca(2+)]i)升高是诱导红细胞发生凋亡的最重要的刺激因素。本研究旨在探讨玉米赤霉烯酮是否能诱导红细胞发生凋亡。用细胞前向散射来评估红细胞体积,用 annexin-V 结合来评估细胞膜磷脂酰丝氨酸的暴露,用血红蛋白释放来评估溶血,用 Fluo3 荧光来评估 [Ca(2+)]i。48 小时暴露于玉米赤霉烯酮(≥25μM)后,细胞内钙离子浓度显著升高,annexin-V 结合显著增加,前向散射显著降低。在不存在细胞外钙离子的情况下,玉米赤霉烯酮对 annexin-V 结合的影响显著减弱。玉米赤霉烯酮刺激红细胞发生自杀性死亡,这一效应至少部分是由于刺激了钙离子内流。

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