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

Abstract

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.

• Authors: Eun Hee Han, Hyung Gyun Kim, Ji Hye Im, Tae Cheon Jeong, Hye Gwang Jeong
• Journal: Toxicology (Toxicology) Vol. 266 Issue 1-3 Pg. 38-47 (Dec 21 2009) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 19853001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide
• Ahr protein, mouse
• Azo Compounds
• Basic Helix-Loop-Helix Transcription Factors
• Chelating Agents
• Drugs, Chinese Herbal
• Indole Alkaloids
• Protein Kinase Inhibitors
• Pyrazoles
• Quinazolines
• RNA, Messenger
• Receptors, Aryl Hydrocarbon
• Sulfonamides
• 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
• Egtazic Acid
• W 7
• rutecarpine
• Cytochrome P-450 CYP1A1
• Calcium-Calmodulin-Dependent Protein Kinases
• Calcium

Topics

• Animals
• Azo Compounds (pharmacology)
• Basic Helix-Loop-Helix Transcription Factors
• Binding Sites
• Calcium (metabolism)
• Calcium-Calmodulin-Dependent Protein Kinases (antagonists & inhibitors, metabolism)
• Cell Line, Tumor
• Chelating Agents (pharmacology)
• Cytochrome P-450 CYP1A1 (biosynthesis, genetics)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (pharmacology)
• Egtazic Acid (analogs & derivatives, pharmacology)
• Enzyme Induction
• Indole Alkaloids (pharmacology)
• Liver (drug effects, enzymology)
• Mice
• Phosphorylation
• Promoter Regions, Genetic (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• Pyrazoles (pharmacology)
• Quinazolines (pharmacology)
• RNA, Messenger (metabolism)
• Receptors, Aryl Hydrocarbon (agonists, antagonists & inhibitors, metabolism)
• Sulfonamides (pharmacology)