Butein Up-Regulates the Expression of the π Class of Glutathione S-Transferase in Rat Primary Hepatocytes through the ERK/AP-1 Pathway

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• 作者：Hebron C. Chang ; Haw-Wen Chen ; Hui-Shan Tung ; Kai-Li Liu ; Chia-Wen Tsai ; Chong-Kuei Lii
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2010
• 出版时间：August 25, 2010
• 年：2010
• 卷：58
• 期：16
• 页码：8994-9000
• 全文大小：868K
• 年卷期：v.58,no.16(August 25, 2010)
• ISSN：1520-5118

文摘

Induction of phase II enzymes is an important mechanism of chemoprevention. Here we compared the effects of chalcones on the expression of the π class of glutathione S-transferase (GSTP) in rat primary hepatocytes. Hepatocytes were treated with 10 or 25 μM of phloretin or butein for 24 h. Both butein and phloretin dose-dependently increased GSTP protein expression, and the induction potency of butein was stronger than that of phloretin. The increase in GSTP mRNA in cells treated with 25 μM of phloretin and butein was 107% and 211%, respectively (P < 0.05). Butein increased GST enzyme activity by 27% compared with that in the control cells (P < 0.05). In contrast, phloretin had no significant effect on GST enzyme activity. The pTA-luciferase reporter construct with the rat −2.7 kb GSTP promoter region was transiently transfected into Clone 9 liver cells, and the luciferase activity in butein-treated cells was 1.1-fold higher than that in control cells (P < 0.05). GSTP enhancer 1 (GPE1) deletion abolished the induction of reporter activity by butein. The phosphorylation of extracellular signal-regulated kinase (ERK), but not of c-Jun NH₂-terminal kinase (JNK) and p38, was stimulated in the presence of butein. Pretreatment with PD98059, an ERK inhibitor, alleviated the increase in activator protein-1 (AP-1)-DNA binding activity and also the activation of GSTP protein expression by butein. Moreover, c-Jun is likely to bind to the GPE1. Silencing of ERK2 by siRNA gene knockdown reduced the butein-induced expression of GSTP. In conclusion, the increased GSTP expression by butein is likely related to the ERK-AP-1 pathway.

Keywords:

Butein; π class of glutathione S-transferase; extracellular signal-regulated kinase; activator protein-1; rat primary hepatocytes