Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network.
Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network.
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MAPK P44/42的早期激活部分参与了Don诱导的肠道屏障功能和紧密连接网络的破坏。
DOI：
10.3390/toxins8090264
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发表时间：
2016-09-08
期刊：
影响因子：
4.2
通讯作者：
Mayer E
中科院分区：
文献类型：
--
作者：
Springler A;Hessenberger S;Schatzmayr G;Mayer E
脱氧雪腐镰刀菌烯醇（DON）是由禾谷镰刀菌（Fusarium graminearum）和黄色镰刀菌（Fusarium culmorum）产生的一种最常见的真菌毒素，污染谷物和谷物衍生产品。尽管世界范围内的食品和饲料污染对人类和动物的健康构成威胁，但猪特别容易受到这种霉菌毒素的影响。DON衍生物，例如去环氧-脱氧雪腐镰刀菌烯醇（DOM-1），通过某些肠道细菌的细菌转化产生，其是天然存在的或用作饲料添加剂。肠上皮细胞是抵抗这些食物和饲料传播的毒素的最初屏障。本研究证实了DON诱导的MAPK p44/42活化和MAPK抑制剂U 0126单乙醇化物对p44/42的抑制。评估DON和DOM-1对跨上皮电阻（TEER）、活力和七种紧密连接蛋白（TJ）表达的影响，以及U 0126对抗DON诱导的作用的潜力。虽然DOM-1没有显示出效果，但DON显著降低了分化的IPEC-J2的TEER，并降低了claudin-1和-3的表达，而使claudin-4; ZO-1，-2和-3和occludin不受影响。抑制p44/42抵消了DON诱导的TEER降低并恢复了claudin-3，但不是claudin-1的表达。因此，DON对TEER和claudin-3的作用至少部分是p44/42介导的，而对活力和claudin-1的作用可能通过替代途径介导。
Deoxynivalenol (DON), produced by the plant pathogens Fusarium graminearum and Fusarium culmorum, is one of the most common mycotoxins, contaminating cereal and cereal-derived products. Although worldwide contamination of food and feed poses health threats to humans and animals, pigs are particularly susceptible to this mycotoxin. DON derivatives, such as deepoxy-deoxynivalenol (DOM-1), are produced by bacterial transformation of certain intestinal bacteria, which are naturally occurring or applied as feed additives. Intestinal epithelial cells are the initial barrier against these food- and feed-borne toxins. The present study confirms DON-induced activation of MAPK p44/42 and inhibition of p44/42 by MAPK-inhibitor U0126 monoethanolate. Influence of DON and DOM-1 on transepithelial electrical resistance (TEER), viability and expression of seven tight junction proteins (TJ), as well as the potential of U0126 to counteract DON-induced effects, was assessed. While DOM-1 showed no effect, DON significantly reduced TEER of differentiated IPEC-J2 and decreased expression of claudin-1 and -3, while leaving claudin-4; ZO-1, -2, and -3 and occludin unaffected. Inhibition of p44/42 counteracted DON-induced TEER decrease and restored claudin-3, but not claudin-1 expression. Therefore, effects of DON on TEER and claudin-3 are at least partially p44/42 mediated, while effects on viability and claudin-1 are likely mediated via alternative pathways.
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影响因子：
3.5
作者：
Diesing, Anne-Kathrin;Nossol, Constanze;Kahlert, Stefan
通讯作者：
Kahlert, Stefan
影响因子：
4.1
作者：
Basuroy, S;Seth, A;Rao, R
通讯作者：
Rao, R
影响因子：
4.8
作者：
Favata, MF;Horiuchi, KY;Trzaskos, JM
通讯作者：
Trzaskos, JM
DOI：
10.1042/bj20100249
发表时间：
2011-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Aggarwal S;Suzuki T;Taylor WL;Bhargava A;Rao RK
通讯作者：
Rao RK
影响因子：
4.3
作者：
Broekaert, Nathan;Devreese, Mathias;Croubels, Siska
通讯作者：
Croubels, Siska