Sulforaphane and α-Lipoic Acid Upregulate the Expression of the π Class of Glutathione S-Transferase through c-Jun and Nrf2 Activation
Sulforaphane and α-Lipoic Acid Upregulate the Expression of the π Class of Glutathione S-Transferase through c-Jun and Nrf2 Activation
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DOI：
10.3945/jn.110.121418
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发表时间：
2010-05-01
影响因子：
4.2
通讯作者：
Tsai, Chia-Wen
中科院分区：
文献类型：
--
作者：
Lii, Chong-Kuei;Liu, Kai-Li;Tsai, Chia-Wen
膳食有机硫化合物的抗癌作用部分归因于其调节II相解毒酶的活性和表达。我们以前的研究表明，大蒜烯丙基硫通过激活蛋白-1途径上调谷胱甘肽S-转移酶（GSTP）的IT类的表达。在这里，我们研究了萝卜硫素（SFN）和α-硫辛酸（LA）或二氢硫辛酸（DHLA）对大鼠克隆银细胞GSTP表达的调节作用。用LA或DHLA（50-600 μ mol/L）或SFN（0.2-5 μ mol/L）处理细胞24小时。免疫印迹和实时定量PCR结果表明，SFN，LA和DHLA剂量依赖性地诱导GSTP蛋白和mRNA的表达。与大蒜有机硫化合物二烯丙基三硫（DAIS）的诱导效果相比，SFN > DAIS > LA = DHLA。5 μ mol/L SFN、50 μ mol/L DAIS、600 μ mol/L LA和DHLA处理组GSTP酶活性分别提高172、75、122和117%（P < 0.051）。报告基因分析表明GSTP增强子I（GPEI）是有机硫化合物诱导GSTP所必需的。电迁移率凝胶位移分析表明，GPEI与核蛋白的DNA结合在SFN，LA和DHLA处理后0.5-1小时达到最大值。超位移分析显示转录因子c-jun和核因子红细胞2相关因子2（nuclear factor erythroid-2 related factor 2，Nrf 2）与GPEI结合。这些结果表明，SFN和LA以其氧化或还原形式通过激活c-jun和Nrf 2结合增强子元件GPEI来上调GSTP基因的转录。J.营养140：885-892，2010.
The anticarcinogenic effect of dietary organosulfur compounds has been partly attributed to their modulation of the activity and expression of phase II detoxification enzymes. Our previous studies indicated that garlic allyl sulfides upregulate the expression of the IT class of glutathione S-transferase (GSTP) through the activator protein-1 pathway. Here, we examined the modulatory effect of sulforaphane (SFN) and alpha-lipoic acid (LA) or dihydrolipoic acid (DHLA) on GSTP expression in rat Clone Sliver cells. Cells were treated with LA or DHLA (50-600 mu mol/L) or SFN (0.2-5 mu mol/L) for 24 h. Immunoblots and real-time PCR showed that SFN, LA, and DHLA dose dependently induced GSTP protein and mRNA expression. Compared with the induction by the garlic organosulfur compound diallyl trisulfide (DAIS), the effectiveness was in the order of SFN > DAIS > LA = DHLA. The increase in GSTP enzyme activity in cells treated with 5 mu mol/L SFN, 50 mu mol/L DAIS, and 600 mu mol/L LA and DHLA was 172, 75, 122, and 117%, respectively (P < 0.051). A reporter assay showed that the GSTP enhancer I (GPEI) was required for GSTP induction by the organosulfur compounds. Electromobility gel shift assays showed that the DNA binding of GPEI to nuclear proteins reached a maximum at 0.5-1 h after SFN, LA, and DHLA treatment. Super-shift assay revealed that the transcription factors c-jun and nuclear factor erythroid-2 related factor 2 (Nrf2) were bound to GPEI. These results suggest that SFN and LA in either its oxidized or reduced form upregulate the transcription of the GSTP gene by activating c-jun and Nrf2 binding to the enhancer element GPEI. J. Nutr. 140: 885-892, 2010.