Suppression of TCDD-induced cytochrome P450 IA1 activity by staurosporine in mouse primary hepatocyte cultures and hepatoma cells.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced cytochrome P450 IA1 activity in mouse primary hepatocyte cultures and mouse hepatoma Hepa-1 cells. Pretreatment with staurosporine, a protein kinase C inhibitor, inhibited TCDD-activated cytochrome P450 IA1 expression dose-dependently in both culture systems. Staurosporine also decreased P450IA1 protein synthesis which was detected using western immunoblot. Increased transcription of CYP1A1 gene by TCDD was also suppressed by staurosporine treatment. However, tyrphostin AG213, a specific tyrosine kinase inhibitor, had no effects on TCDD-induced cytochrome P450 expression. These results suggest that protein kinase C signal transduction may be involved in the cytochrome P450 induction mechanism by TCDD.
Chun
Y J
YJ
Department of Life Science, Korea Advanced Institute of Science and Technology (KAIST), Taejon.
Koh
W S
WS
Yang
K H
KH
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002396:Catechols / Q000494:pharmacology; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009570:Nitriles / Q000494:pharmacology; D010088:Oxidoreductases / Q000096:biosynthesis; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D014407:Tumor Cells, Cultured; D020032:Tyrphostins
D000470:Alkaloids; D002396:Catechols; D009570:Nitriles; D000072317:Polychlorinated Dibenzodioxins; D020032:Tyrphostins; C060152:tyrphostin 47; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine