Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells.
Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells.
复制标题
哺乳动物细胞中载体介导且能量依赖性的脱氧雪腐镰刀菌烯醇的摄取和流出
DOI：
10.1038/s41598-017-06199-8
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发表时间：
2017-07-19
影响因子：
4.6
通讯作者：
Deng Y
中科院分区：
文献类型：
--
作者：
Li X;Mu P;Wen J;Deng Y
脱氧雪腐镰刀菌醇（DON）是最丰富的真菌毒素之一，对人类和动物产生许多不良影响。迄今为止，DON在哺乳动物细胞中的转运机制尚不清楚。本研究通过平行人工膜通透性实验（PAMPA）、Transwell模型和代谢抑制剂来确定DON在Caco-2、MDCK和HepG2细胞中的可能转运机制。PAMPA和Transwell模型显示被动转运减少，肠道吸收增加，提示载体介导的转运机制。此外，在基底外侧到根尖的方向上，DON的单向转运高于根尖到基底外侧的方向，这表明存在外排蛋白。有趣的是，DON在细胞核中积累，而在线粒体中没有检测到DON，这表明细胞核可能是DON的主要靶细胞器。此外，各种转运蛋白抑制剂在不同细胞中的使用表明，有机阴离子转运蛋白、有机阳离子转运蛋白和有机阴离子转运多肽参与DON摄取，p -糖蛋白是主要的外排蛋白。重要的是，DON的摄取受到代谢抑制剂的强烈抑制，并且高度依赖于温度。总之，本文报道了哺乳动物细胞中DON的载体介导和能量依赖性摄取和外排机制，有助于提高我们对其毒理学机制的理解。
Deoxynivalenol (DON) is one of the most abundant mycotoxins and exerts many adverse effects on humans and animals. To date, the transporting mechanism of DON in mammalian cells remains unclear. In this study, the parallel artificial membrane permeability assay (PAMPA), Transwell models and metabolic inhibitors were used to determine the possible transporting mechanisms of DON in Caco-2, MDCK and HepG2 cells. PAMPA and Transwell models showed reduced passive transport and increased intestinal absorption, indicating a carrier-mediated transporting mechanism. Furthermore, higher unidirectional transport of DON was observed in the basolateral-to-apical direction than in the apical-to-basolateral direction, indicating the existence of efflux proteins. Interestingly, DON was accumulated in the nucleus, and no DON was detected in mitochondria, indicating that the nucleus may be the main target organelle of DON. Moreover, the use of various transporter inhibitors in different cells shows that organic anion transporters, organic cation transporters, and organic anion-transporting polypeptides participate in DON uptake, and P-glycoprotein is the major efflux protein. Importantly, DON uptake is strongly inhibited by metabolic inhibitors and is highly dependent on temperature. In summary, carrier-mediated and energy-dependent uptake and efflux mechanisms for DON in mammalian cells are reported, aiding in improving our understanding of its toxicological mechanisms.