Sulforaphane and its glutathione conjugate but not sulforaphane nitrile induce UDP-glucuronosyl transferase (UGT1A1) and glutathione transferase (GSTA1) in cultured cells
Sulforaphane and its glutathione conjugate but not sulforaphane nitrile induce UDP-glucuronosyl transferase (UGT1A1) and glutathione transferase (GSTA1) in cultured cells
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DOI：
10.1093/carcin/23.8.1399
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发表时间：
2002-08-01
期刊：
影响因子：
4.7
通讯作者：
Williamson, G
中科院分区：
文献类型：
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作者：
Basten, GP;Bao, YP;Williamson, G
芸苔属蔬菜中的萝卜硫素根据条件分解为萝卜硫素或萝卜硫素腈，并且萝卜硫素可以进一步与谷胱甘肽结合。采用高通量微量滴定板法和TaqMan真实的时间定量RT-PCR检测mRNA，我们发现萝卜硫素及其谷胱甘肽结合物，而不是腈，在HepG 2和HT 29细胞中显著增加UGT 1A 1和GSTA 1 mRNA水平（P < 0.05）。这些变化伴随UGT 1A 1蛋白增加（通过免疫印迹法评估）和胆红素葡萄糖醛酸化增加2-8倍。当一起处理时，腈衍生物不影响萝卜硫素诱导。莱菔硫烷对UGT 1A 1和GSTA 1 mRNA的诱导具有时间和浓度依赖性。结果表明，萝卜硫素，但不是萝卜硫素腈的葡萄糖醛酸化的功能性诱导，并表明，芥子油苷在芸苔属蔬菜的代谢途径是重要的，在确定所产生的生物和抗癌活性。
Glucoraphanin in Brassica vegetables breaks down to either sulforaphane or sulforaphane nitrile depending on the conditions, and sulforaphane can be further conjugated with glutathione. Using a high-throughput microtitre plate assay and TaqMan real time quantitative RT-PCR to measure mRNA, we show that sulforaphane and its glutathione conjugate, but not the nitrile, increased significantly (P < 0.05) both UGT1A1 and GSTA1 mRNA levels in HepG2 and HT29 cells. These changes were accompanied by an increase in UGT1A1 protein, as assessed by immunoblotting, and a 2-8-fold increase in bilirubin glucuronidation. When treated together, the nitrile derivative did not affect sulforaphane induction. The induction of UGT1A1 and GSTA1 mRNA by sulforaphane was time and concentration dependent. The results show a functional induction of glucuronidation by sulforaphane but not sulforaphane nitrile, and show that the pathway of metabolism of glucosinolates in Brassica vegetables is important in determining the resulting biological and anticarcinogenic activities.