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Non-electrophilic TRPA1 agonists, menthol, carvacrol and clotrimazole, open epithelial tight junctions via TRPA1 activation.
The Journal of Biochemistry ( IF 2.7 ) Pub Date : 2020 , DOI: 10.1093/jb/mvaa057
Minagi Mukaiyama 1 , Takeo Usui 2, 3 , Yoko Nagumo 2, 4
Affiliation  

Abstract
Activation of the transient receptor potential A1 channel (TRPA1) by electrophilic agonists was reported to induce the opening of tight junctions (TJs). Because compounds that increase TJ permeability can be paracellular permeability enhancers, we investigated the effect of non-electrophilic TRPA1 activators, including food ingredients (menthol and carvacrol) and medication (clotrimazole), on epithelial permeability. We show that all three compounds induced increase of the permeability of fluorescein isothiocyanate-conjugated dextran (4 kDa) and decrease of transepithelial electrical resistance, accompanied by Ca2+ influx and cofilin activation in epithelial MDCK II monolayers. These phenotypes were attenuated by pretreatment of a TRPA1 antagonist, suggesting TRPA1-mediated opening of TJs. These results suggest that non-electrophilic TRPA1 activators with established safety can be utilized to regulate epithelial barriers.


中文翻译:

非亲电性TRPA1激动剂,薄荷醇,香芹酚和克霉唑通过TRPA1激活打开上皮紧密连接。

摘要
据报道,亲电激动剂激活瞬时受体电位A1通道(TRPA1)会诱导紧密连接(TJ)的打开。因为增加TJ通透性的化合物可以是细胞旁通透性增强剂,所以我们研究了非亲电子TRPA1激活剂(包括食品成分(薄荷醇和香芹酚)和药物(克霉唑))对上皮通透性的影响。我们表明,所有这三种化合物诱导荧光素异硫氰酸酯共轭右旋糖酐(4 kDa)的渗透性增加和跨上皮电阻的降低,并伴有Ca 2+上皮MDCK II单层细胞的内流和cofilin激活。这些表型通过TRPA1拮抗剂的预处理而减弱,表明TRPA1介导的TJ的开放。这些结果表明具有确定的安全性的非亲电子TRPA1激活剂可用于调节上皮屏障。
更新日期:2020-10-27
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