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姜黄素对谷胱甘肽S-转移酶和NADP(H):醌氧化还原酶诱导作用及其可能的作用机制

Effect of curcumin on the induction of glutathione S-transferases and NADP(H):quinone oxidoreductase and its possible mechanism of action.

作者信息

Ye She-fang, Hou Zhen-qing, Zhong Li-ming, Zhang Qi-qing

机构信息

Key Laboratory of Biomedical Engineering of Fujian, Medical College, Xiamen University, Xiamen 361005, China.

出版信息

Yao Xue Xue Bao. 2007 Apr;42(4):376-80.

PMID:17633203
Abstract

This study is to investigate the effect of curcumin on the induction of glutathione S-transferases (GST) and NADP(H):quinone oxidoreductase (NQO) and explore their possible molecular mechanism. The activity of GST, NQO and cellular reduced glutathione (GSH) content were measured by spectrophotometrical methods. Cellular changes in the distribution of NF-E2 related factor 2 (Nrf2) were detected by Western blotting analysis. Nrf2-AREs (antioxidant-responsive elements) binding activity was examined by electrophoretic mobility shift assay (EMSA). Treatment of HT-29 human colon adenocarcinoma cells with curcumin dramatically induced the activity of GST and NQO at the range of 10-30 micromol x L(-1). Curcumin exposure caused a significant increase in cellular GSH content rapidly as early as 3 h. Moreover, curcumin triggered the accumulation of Nrf2 in nucleus, and increased Nrf2 content in ARE complexes. These results demonstrated that induction of GST and NQO activity by curcumin may be mediated by translocation of transcription factor Nrf2 from cytoplasm to nuclear and increased binding activity of Nrf2-ARE complexes.

摘要

本研究旨在探讨姜黄素对谷胱甘肽S-转移酶(GST)和NADP(H):醌氧化还原酶(NQO)诱导作用的影响,并探究其可能的分子机制。采用分光光度法测定GST、NQO的活性以及细胞内还原型谷胱甘肽(GSH)的含量。通过蛋白质免疫印迹分析检测NF-E2相关因子2(Nrf2)分布的细胞变化。采用电泳迁移率变动分析(EMSA)检测Nrf2-抗氧化反应元件(AREs)的结合活性。用姜黄素处理HT-29人结肠腺癌细胞,在10 - 30 μmol·L⁻¹范围内显著诱导了GST和NQO的活性。早在3小时,姜黄素暴露就迅速导致细胞内GSH含量显著增加。此外,姜黄素引发了Nrf2在细胞核中的积累,并增加了ARE复合物中Nrf2的含量。这些结果表明,姜黄素对GST和NQO活性的诱导作用可能是通过转录因子Nrf2从细胞质向细胞核的转位以及Nrf2-ARE复合物结合活性的增加来介导的。

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