Rat hepatic CYP1A1 and CYP1A2 induction by menadione.
The effects of menadione on activities and expression of cytochrome P450 (CYP) 1A subfamily (CYP1A) isozymes in rat hepatic tissue were examined. When rats were treated orally with 15 mg/kg menadione for 4 days, the elevation of hepatic CYP1A1/1A2 specific activities in microsomal preparations was detected with approximately 5.4- and 2.5-fold increase over control values for ethoxyresorufin-O-deethylase (EROD, CYP1A1) and methoxyresorufin-O-demethylase (MROD, CYP1A2) activities, respectively. CYP1A1 and CYP1A2 mRNA levels in the liver of menadione-treated rats were approximately 11.8- and 1.8-fold higher than in controls, respectively, whereas the expression of the CYP1A regulatory proteins aryl hydrocarbon-receptor (AhR) and AhR nuclear translocator (Arnt) was not changed at the mRNA level. The result of this study demonstrates that menadione induces CYP1A1/1A2 expression in vivo through either transcriptional activation and/or mRNA stabilization.
Sidorova
Y A
YA
Institute of Molecular Biology and Biophysics, Siberian Division of Russian Academy of Medical Sciences, Timakova str. 2, Novosibirsk 630090, Russia. ysidorova@soramn.ru
Grishanova
A Y
AY
Lyakhovich
V V
VV
D000199:Actins / Q000096:biosynthesis; D000284:Administration, Oral; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis; D024483:Vitamin K 3 / Q000633:toxicity*
C497398:ARNT protein, rat; D000199:Actins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D024483:Vitamin K 3; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2