Effect of aflatoxin B1 on UDP-glucuronosyltransferase mRNA expression in HepG2 cells
Effect of aflatoxin B1 on UDP-glucuronosyltransferase mRNA expression in HepG2 cells
复制标题
DOI：
10.1016/j.chemosphere.2012.05.039
复制
发表时间：
2012-10-01
期刊：
影响因子：
8.8
通讯作者：
Narimatsu, Shizuo
中科院分区：
文献类型：
--
作者：
Hanioka, Nobumitsu;Nonaka, Yuko;Narimatsu, Shizuo
黄曲霉毒素B1（AFB 1）是一种强效真菌毒素，可诱导包括人类在内的许多动物发生肝细胞癌。在这项研究中，我们研究了黄曲霉毒素B1对UDP-葡萄糖醛酸转移酶（UGT）mRNA表达的影响在HepG 2细胞（人肝癌细胞系）。用浓度为10 μ M的黄曲霉毒素B1处理细胞48小时，其存活率（87%）与对照细胞无显著差异。逆转录聚合酶链反应（RT-PCR）分析表明，4种UGT 1A（UGT 1A 1、UGT 1A 3、UGT 1A 4和UGT 1A 9）和7种UGT 2B（UGT 2B 4、UGT 2B 7、UGT 2B 10、UGT 2B 11、UGT 2B 15、UGT 2B 17和UGT 2B 28）的mRNA在HepG 2细胞中表达。还检测了作为转录调节因子的芳烃受体（AhR）、孕烷X受体（PXR）、维甲酸X受体（RXR）和糖皮质激素受体（GR）的mRNA。AFB 1显著增加HepG 2细胞中UGT 1A 3、UGT 2B 10、UGT 2B 15和UGT 2B 17的mRNA水平，分别为2.5、2.0、1.9和1.5倍，而转录调节因子的mRNA水平几乎不受AFB 1的影响。这些结果表明，AFB 1诱导UGT 2B亚型，而不是UGT 1A亚型在HepG 2细胞，这种变化可能密切有助于AFB 1的毒性。(C)2012爱思唯尔有限公司保留所有权利。
Aflatoxin B1 (AFB1) is a potent mycotoxin that induces hepatocellular carcinoma in many animal species, including humans. In this study, we examined the effects of AFB1 on UDP-glucuronosyltransferase (UGT) mRNA expression in HepG2 cells (human hepatocellular carcinoma cell line). The cells were treated with AFB1 for 48 h at a concentration of 10 mu M, and their viability (87%) was not significantly different from that of control cells. Reverse transcription polymerase chain reaction (RT-PCR) analysis demonstrated that the mRNAs of four UGT1As (UGT1A1, UGT1A3, UGT1A4 and UGT1A9) and seven UGT2Bs (UGT2B4, UGT2B7, UGT2B10, UGT2B11, UGT2B15, UGT2B17 and UGT2B28) are expressed in HepG2 cells. The mRNAs of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), retinoid X receptor (RXR) and glucocorticoid receptor (GR) as transcriptional regulators were also detected. AFB1 significantly increased mRNA levels of UGT1A3, UGT2B10, UGT2B15 and UGT2B17 in HepG2 cells to 2.5-, 2.0-, 1.9- and 1.5-fold, respectively, whereas the mRNA levels of transcriptional regulators were hardly affected by AFB1. These findings suggest that AFB1 induces UGT2B isoforms rather than UGT1A isoforms in HepG2 cells, and that the change may closely contribute to the toxicity of AFB1. (C) 2012 Elsevier Ltd. All rights reserved.