Up-regulation of CYP1A1 by rutaecarpine is dependent on aryl hydrocarbon receptor and calcium

作者：Han Eun Hee; Kim Hyung Gyun; Im Ji Hye; Jeong Tae Cheon; Jeong Hye Gwang^*

来源：Toxicology, 2009, 266(1-3): 38-47.

DOI：10.1016/j.tox.2009.10.013

• Rutaecarpine
• CYP1A1
• Aryl hydrocarbon receptor
• Calcium

Rutaecarpine is a quinazolinocarboline alkaloid isolated from a traditional Chinese medicinal fruit, Evodia rutaecarpa. In the present study, we investigated the effect of rutaecarpine on CYP1A1 expression mediated by [Ca(2 )] and the AhR pathway in mouse hepatoma Hepa-1c1c7 cells. Rutaecarpine also significantly increased CYP1A1 enzyme activity and mRNA and protein levels. Rutaecarpine markedly induced XRE and AhR binding activity. CH-223191, an AhR antagonist, blocked the rutaecarpine-induced CYP1A1 enzyme activity and mRNA and protein expression. In addition, rutaecarpine remarkably induced the phosphorylation of Ca(2 )/calmodulin (CaM)-dependent protein kinase (CaMK). W7 and BAPTA/AM, a CaM antagonist and an intracellular Ca(2 ) chelator, respectively, blocked the rutaecarpine-induced CYP1A1 enzyme activity and mRNA and protein expression. These results indicate that rutaecarpine induces CYP1A1 expression through AhR- and calcium-dependent mechanisms.

• 出版日期2009-12-21