Up-regulation of CYP1A1 by rutaecarpine is dependent on aryl hydrocarbon receptor and 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.
Department of Toxicology, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-Gu, Daejeon 305-764, South Korea.
Eun Hee
EH
Han
Hyung Gyun
HG
Kim
Ji Hye
JH
Im
Tae Cheon
TC
Jeong
Hye Gwang
HG
Jeong
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004790:Enzyme Induction; D026121:Indole Alkaloids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D052999:Quinazolinones
D001391:Azo Compounds; D051792:Basic Helix-Loop-Helix Proteins; D002118:Calcium; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002614:Chelating Agents; D019363:Cytochrome P-450 CYP1A1; D004365:Drugs, Chinese Herbal; D004533:Egtazic Acid; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011799:Quinazolines; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D013449:Sulfonamides; C511621:2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide; C484722:Ahr protein, mouse; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C017967:W 7; C028632:rutecarpine; D052999:Quinazolinones