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Vol. 292, Issue 3, 1008-1014, March 2000

Induction of Cytochrome P-450 1A2 by Oxidized Tryptophan in Hepa lclc7 Cells1

Ram K. Sindhu, Masato Mitsuhashi and Yutaka Kikkawa

Department of Pathology, College of Medicine, University of California-Irvine, Irvine, California

Recent studies from this laboratory have demonstrated that L-tryptophan, after oxidation either by UV-irradiation or ozone, induces aryl hydrocarbon receptor (AhR) activation and binding of the liganded AhR complex to its specific DNA recognition site, thereby initiating transcription of the cytochrome P-450 1a1 (Cyp1a1) gene with concomitant increase of CYP1A1 protein and 7-ethoxyresorufin O-deethylase activity in wild-type mouse hepatoma cells, Hepa lclc7 (Hepa-1), in culture. Temporary inhibition of protein synthesis by cycloheximide resulted in superinduction of oxidized tryptophan-inducible CYP1A1 mRNA, protein, and 7-ethoxyresorufin O-deethylase activity in Hepa-1 cells. In the present communication, the results obtained by immunoblot analyses with monoclonal CYP1A1/1A2 antibody (NIH 1-7-1) demonstrate that both UV- or ozone-oxidized tryptophan also induce CYP1A2 protein in Hepa-1 cells. CYP1A2 mRNA, detected by reverse transcription-polymerase chain reaction, was markedly induced in the UV- or ozone-oxidized tryptophan-treated cells. Temporary inhibition of protein synthesis by cycloheximide further induced oxidized tryptophan-inducible CYP1A2 mRNA as well as the protein in Hepa-1 cells. This is the first report demonstrating the induction of CYP1A2 mRNA and protein in Hepa-1 cells.

1 This work was supported by Grant HL-50450 from the National Heart, Lung and Blood Institute of the National Institutes of Health, U.S. Public Health Service.

0022-3565/00/2923-1008$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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