Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5.
Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2)-deficient (Nrf2(-⧸-)) mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2(-⧸-) mouse livers were lower than that in wild-type mouse livers. Nrf2(-⧸-) mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression.
Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Takashi
T
Ashino
Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Haruyo
H
Ohkubo-Morita
Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Masayuki
M
Yamamoto
Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Takemi
T
Yoshida
Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Satoshi
S
Numazawa
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics; D007659:Ketones / Q000008:administration & dosage* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010634:Phenobarbital / Q000008:administration & dosage* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013250:Steroid Hydroxylases / Q000235:genetics*
D007659:Ketones; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C018637:phorone; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C585520:Cyp2a5 protein, mouse; C101679:Cyp2b10 protein, mouse; D000072467:Cytochrome P450 Family 2; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D016660:NAD(P)H Dehydrogenase (Quinone); C000597536:Noq1 protein, mouse; D010634:Phenobarbital
ARE, antioxidant response element; CAR, constitutive androstane receptor; Cyp2a5; Cyp2b10; Gapdh, glyceraldehyde-3-phosphate dehydrogenase; Hmox1, heme oxygenase-1; Maf, musculoaponeurotic fibrosarcoma oncogene homolog; Mouse; Nqo1, NAD(P)H-quinone oxidoreductase-1; Nrf2, nuclear-factor erythroid 2-related factor 2; Nuclear-factor erythroid 2-related factor 2; P450, cytochrome P450; PBREM, phenobarbital responsive element module; PCR, polymerase chain reaction; Phenobarbital; Phorone