Mycotoxin deoxynivalenol (DON) mediates biphasic cellular response in intestinal porcine epithelial cell lines IPEC-1 and IPEC-J2
Mycotoxin deoxynivalenol (DON) mediates biphasic cellular response in intestinal porcine epithelial cell lines IPEC-1 and IPEC-J2
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DOI：
10.1016/j.toxlet.2010.10.006
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发表时间：
2011-01-15
影响因子：
3.5
通讯作者：
Kahlert, Stefan
中科院分区：
文献类型：
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作者：
Diesing, Anne-Kathrin;Nossol, Constanze;Kahlert, Stefan
镰刀菌衍生的真菌毒素脱氧雪腐镰刀菌醇（DON）经常存在于用于人类和动物营养的谷物中。我们研究了低浓度（200 ng/mL）和高浓度（2000 ng/mL）下DON对猪小肠源性非转化、非癌、极化上皮细胞（IPEC-1和IPEC-J2）的影响。高浓度DON的应用显示出明显的毒性作用，如细胞数量减少、MTT测定的细胞还原能力下降、中性红（NR）摄取减少和细胞增殖减少。高剂量毒性表现为紧密连接蛋白ZO-1的崩解和细胞周期G2/M期的延长。caspase 3的激活是在高DON浓度下的早期事件，在6-8 h后达到初始最大值。相比之下，200 ng/mL DON的应用表现出与高剂量DON毒性不同的反应模式。细胞周期、ZO-1的表达和分布以及caspase 3的激活均未发生变化。在200 ng/mL DON孵育72 h后，BrdU掺入显著增加，而NR摄取仅在24 h后短暂减少。低剂量DON对肠上皮细胞的影响由不同于高剂量毒性的机制触发。2010爱思唯尔爱尔兰有限公司版权所有。
The Fusarium derived mycotoxin deoxynivalenol (DON) is frequently found in cereals used for human and animal nutrition. We studied effects of DON in non-transformed, non-carcinoma, polarized epithelial cells of porcine small intestinal origin (IPEC-1 and IPEC-J2) in a low (200 ng/mL) and a high (2000 ng/mL) concentration. Application of high DON concentrations showed significant toxic effects as indicated by a reduction in cell number, in cellular reduction capacity measured by MTT assay, reduced uptake of neutral red (NR) and a decrease in cell proliferation. High dose toxicity was accompanied by disintegration of tight junction protein ZO-1 and increase of cell cycle phase G2/M. Activation of caspase 3 was found as an early event in the high DON concentration with an initial maximum after 6-8 h. In contrast, application of 200 ng/mL DON exhibited a response pattern distinct from the high dose DON toxicity. The cell cycle, ZO-1 expression and distribution Ss well as caspase 3 activation were not changed. BrdU incorporation was significantly increased after 72 h incubation with 200 ng/mL DON and NR uptake was only transiently reduced after 24 h. Low dose effects of DON on intestinal epithelial cells were triggered by mechanisms different from those responsible for the high dose toxicity. (C) 2010 Elsevier Ireland Ltd. All rights reserved.