Activation of the cAMP/CREB/Inducible cAMP Early Repressor Pathway Suppresses Andrographolide-Induced Gene Expression of the pi Class of Glutathione S-Transferase in Rat Primary Hepatocytes

作者：Yang Ai Jen; Li Chien Chun; Lu Chia Yang; Liu Kai Li; Tsai Chia Wen; Lii Chong Kuei^*; Chen Haw Wen

来源：Journal of Agricultural and Food Chemistry, 2010, 58(3): 1993-2000.

DOI：10.1021/jf902221j

• Andrographolide
• cAMP/CREB/ICER pathway
• forskolin
• pi class of glutathione S-transferase (GSTP)
• hepatocytes

Andrographolide (Ap) is a bioactive compound in Andrographis paniculata that is a Chinese herb. The pi class of glutathione S-transferase (GSTP) is one kind of phase II detoxification enzyme. Here we show that induction of GSTP protein and mRNA expression in rat primary hepatocytes by Ap was inhibited by forskolin and a variety of cAMP analogues. The inhibitory effect of the cAMP analogues was partially blocked by pretreatment with H89. In the presence of Ap, forskolin, or both, the expression of phospho-cAMP response element-binding protein (CREB) was increased. Ap alone had no effect on inducible cAMP early repressor (ICER) mRNA expression; however, Ap played a potentiating role in forskolin-induced ICER mRNA expression. An EMSA and immunoprecipitation assay showed that ICER binding to cAMP-response element (CRE) was increased in cells cotreated with Ap and forskolin for 3 and 8 h. Taken together, these results suggest that ICER is likely to be involved in the suppression of Ap-induced GSTP expression caused by the increase of cAMP in rat primary hepatocytes.

• 出版日期2010-2-10
• 单位中国医科大学