Benzyl isothiocyanate ameliorates acetaldehyde-induced cytotoxicity by enhancing aldehyde dehydrogenase activity in murine hepatoma Hepa1c1c7 cells
Benzyl isothiocyanate ameliorates acetaldehyde-induced cytotoxicity by enhancing aldehyde dehydrogenase activity in murine hepatoma Hepa1c1c7 cells
复制标题
DOI：
10.1016/j.fct.2017.08.016
复制
发表时间：
2017-10-01
影响因子：
4.3
通讯作者：
Nakamura, Yoshimasa
中科院分区：
文献类型：
--
作者：
Liu, Yujia;Yamanaka, Momoko;Nakamura, Yoshimasa
在本研究中，我们评估了异硫氰酸苄酯（BITC），一种有机硫化合物从十字花科蔬菜，作为一个潜在的诱导剂的醛脱氢酶（ALDH）活性使用小鼠肝癌Hepa 1c 1c 7细胞。BITC被证明不仅提高总ALDH活性，而且提高细胞质/微粒体和线粒体组分的ALDH活性。BITC还以浓度依赖性方式显著增加ALDH 1A 1、ALDH 2和ALDH 3A 1的基因和蛋白表达。同时，BITC处理增加了2相药物代谢酶的基因表达，如NAD（P）H：醌氧化还原酶1和血红素加氧酶-1。Western blot结果显示，BITC不仅能上调Nrf 2蛋白的表达，而且能促进Nrf 2的核转位。此外，沉默Nrf 2降低了ALDH的总活性和基因表达的基础和BITC增强水平。BITC的预处理完全减轻了因沉默Nrf 2而受损的乙酰胺诱导的细胞毒性。本研究表明，BITC已被确定为一个潜在的总ALDH活性的诱导剂，以防止乙酰丙酮酸诱导的细胞毒性。(C)2017爱思唯尔有限公司版权所有
In the present study, we assessed benzyl isothiocyanate (BITC), an organosulfur compound from cruciferous vegetables, as a potential inducer of aldehyde dehydrogenase (ALDH) activity using murine hepatoma Hepa1c1c7 cells. BITC was shown to enhance not only the total ALDH activity, but also the ALDH activity of the cytosolic/microsomal and mitochondrial fraction. BITC also significantly increased the gene and protein expression of ALDH1A1, ALDH2 and ALDH3A1 in a concentration-dependent manner. Simultaneously, the gene expression of phase 2 drug-metabolizing enzymes, such as NAD(P)H: quinone oxidoreductase 1 and heme oxygenase-1, was increased by the BITC treatment. Western blot experiments revealed that BITC not only up-regulated the Nrf2 protein expression, but also stimulated the nuclear translocation of Nrf2. Furthermore, silencing Nrf2 reduced the basal and BITC-enhanced levels of the total activity and gene expression of ALDHs. The pretreatment of BITC completely mitigated the acetaldehyde-induced cytotoxicity, which was impaired by silencing Nrf2. The present study demonstrated that BITC has been identified as a potential inducer of the total ALDH activity to prevent the acetaldehyde-induced cytotoxicity. (C) 2017 Elsevier Ltd. All rights reserved.