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Rat hepatic CYP1A1 and CYP1A2 induction by menadione
Y A Sidorova1, A Y Grishanova, V V Lyakhovich
1Institute of Molecular Biology and Biophysics, Siberian Division of Russian Academy of Medical Sciences, Timakova str. 2, Novosibirsk 630090, Russia. ysidorova@soramn.ru
Abstract:
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.
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