Interaction of 1-ethynylpyrene and hepatic CYPIA1 from rainbow trout.
1-Ethynylpyrene (EP) inhibits microsomal 7-ethoxyresorufin O-deethylase (EROD) activities from the liver of both trout and rat. Trout hepatocytes treated with EP had increased microsomal EROD activity and a concomitant increase in CYPIA1 protein as measured by Western blot analysis. EP at 10(-9)-10(-6) M did not interfere with beta-naphthoflavone (BNF) induction of CYPIA1 in trout hepatocytes. In contrast, treatment with alpha-naphthoflavone (ANF), another inhibitor of CYPIA1, resulted in a significant inhibition of the basal (at 10(-6) M ANF) and BNF induced (at 10(-8) M and higher concentrations of ANF) level of EROD activity. ANF also did not significantly induce CYPIA1 protein but led to attenuation of the induction of CYPIA1 proteins by BNF in trout hepatocyte cultures. Thus, in trout hepatocytes, EP acts differently from ANF in the modulation of CYPIA1.
Lee
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PC
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
Dasmahaptra
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AK
D000704:Analysis of Variance; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D007700:Kinetics; D008099:Liver / Q000166:cytology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D017686:Oncorhynchus mykiss; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D011721:Pyrenes / Q000494:pharmacology*; D051381:Rats; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D065607:Cytochrome P-450 Enzyme Inhibitors; D011721:Pyrenes; C042881:1-ethynylpyrene; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1