Induction of cytochrome P-4502B1-related mouse cytochrome P-450 and regulation of its expression by epidermal growth factor/transforming growth factor alpha in primary hepatocyte culture.
Phenobarbital-dependent induction of mouse cytochrome P-450 (Cyp) orthologous to rat CYP2B1 and its modulation by hepatotrophic growth factors were examined in primary hepatocyte cultures. Compared to rat hepatocytes, induction in mouse hepatocytes was more rapid and effective. Ligands of the EGF receptor, epidermal growth factor, and transforming growth factor alpha inhibited induction on the basis of protein expression and CYP2B-associated 7-pentoxyresorufin-O-depentylase activity. Furthermore, EGF led to repression of accumulation of corresponding mRNA under phenobarbital, an effect not blocked by inhibition of protein synthesis under cycloheximide. Ligands of the EGF receptor may contribute towards the decrease in hepatic CYP expression observed during (pre)neoplastic development and regeneration.
Aubrecht
J
J
Institute of Pharmacology and Toxicology, University of Göttingen, Germany.
Hirsch-Ernst
K I
KI
Becker-Rabbenstein
V
V
Kahl
G F
GF
Taniguchi
H
H
Höhne
M W
MW
D000818:Animals; D000911:Antibodies, Monoclonal; D001189:Aryl Hydrocarbon Hydroxylases; D002478:Cells, Cultured; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000276:immunology; D004790:Enzyme Induction; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010088:Oxidoreductases / Q000096:biosynthesis; D010634:Phenobarbital; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000276:immunology; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019362:Cytochrome P-450 CYP2B1; C025619:steroid 16-beta-hydroxylase; D010634:Phenobarbital