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.
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.
Yang
Ai-Jen
AJ
Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan.
Li
Chien-Chun
CC
Lu
Chia-Yang
CY
Liu
Kai-Li
KL
Tsai
Chia-Wen
CW
Lii
Chong-Kuei
CK
Chen
Haw-Wen
HW
D035685:Andrographis / Q000737:chemistry; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
C497412:Crem protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D004224:Diterpenes; D010936:Plant Extracts; D051786:Cyclic AMP Response Element Modulator; C030419:andrographolide; D000242:Cyclic AMP; D051549:Glutathione S-Transferase pi