TrxR1 and GPx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death
TrxR1 and GPx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death
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DOI：
10.1016/j.bbamcr.2012.07.007
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发表时间：
2012-10-01
影响因子：
5.1
通讯作者：
Bao, Yongping
中科院分区：
文献类型：
--
作者：
Barrera, Lawrence N.;Cassidy, Aedin;Bao, Yongping
目前，人们对饮食-基因相互作用以及食物化合物调节基因表达以改变癌症易感性的机制领域有着极大的兴趣。从营养的角度来看，两个关键成分可能发挥癌症化学预防作用：异硫氰酸酯（ITC），存在于十字花科蔬菜，硒（Se），作为硒代半胱氨酸，是硒蛋白的一个组成部分。然而，这些化合物的作用，表达的关键硒酶，一旦癌症的过程已经开始仍然需要阐明。因此，本研究探讨了两种形式的硒，硒-甲基硒代半胱氨酸和亚硒酸钠，无论是单独和组合与两个ITCs，萝卜硫素或伊贝林，对表达的两个硒酶，硫氧还蛋白还原酶1（TrxR 1）和胃肠道谷胱甘肽过氧化物酶（GPx 2），这是ITCs的目标，在Caco-2细胞。与ITCs和硒共同处理诱导TrxR 1和GPx 2的表达比单独使用任何一种化合物都要多。此外，预处理的细胞与ITC+硒增强对H2 O2诱导的细胞死亡，通过ROS依赖的机制的细胞保护。此外，TrxR 1和/或GPx 2的单次和双次敲除表明这两种硒蛋白都负责保护免受H2 O2诱导的细胞死亡。总之，这些数据揭示了新的光ITC和硒之间的相互作用的机制，其中前者的翻译表达的增强转录依赖于足够的硒供应，从而导致对细胞死亡的合作抗氧化保护作用。(C)2012 Elsevier ay. All rights reserved.
Currently, there is significant interest in the field of diet-gene interactions and the mechanisms by which food compounds regulate gene expression to modify cancer susceptibility. From a nutrition perspective, two key components potentially exert cancer chemopreventive effects: isothiocyanates (ITCs), present in cruciferous vegetables, and selenium (Se) which, as selenocysteine, is an integral part of selenoproteins. However, the role of these compounds in the expression of key selenoenzymes once the cancer process has been initiated still needs elucidation. Therefore, this investigation examined the effect of two forms of selenium, selenium-methylselenocysteine and sodium selenite, both individually and in combination with two ITCs, sulforaphane or iberin, on the expression of the two selenoenzymes, thioredoxin reductase 1 (TrxR1) and gastrointestinal glutathione peroxidase (GPx2), which are targets of ITCs, in Caco-2 cells. Co-treatment with both ITCs and Se induced expression of TrxR1 and GPx2 more than either compound alone. Moreover, pre-treatment of cells with ITC+Se enhanced cytoprotection against H2O2-induced cell death through a ROS-dependent mechanism. Furthermore, a single and double knockdown of TrxR1 and/or GPx2 suggested that both selenoproteins were responsible for protecting against H2O2-induced cell death. Together, these data shed new light on the mechanism of interactions between ITC and Se in which translational expression of the enhanced transcripts by the former is dependent on an adequate Se supply, resulting in a cooperative antioxidant protective effect against cell death. (C) 2012 Elsevier ay. All rights reserved.