JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Donato, M. T.
Right arrow Articles by Castell, J. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Donato, M. T.
Right arrow Articles by Castell, J. V.

Vol. 284, Issue 2, 760-767, February 1998

Human Hepatocyte Growth Factor Down-regulates the Expression of Cytochrome P450 Isozymes in Human Hepatocytes in Primary Culture1

M. Teresa Donato, M. José Gómez-Lechón, Ramiro Jover, Toshikazu Nakamura and José V. Castell

Unidad de Hepatología Experimental, Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain (M.T.D., M.J.G.-L., R.J., J.V.C.) and Department of Oncology, Biochemical Research Center, Osaka University Medical School, Osaka 565, Japan (T.N.)

This study examines the effects of recombinant human hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, on the cytochrome P450 (CYP) system and conjugating reactions in cultured human hepatocytes. The time course of HGF effects on CYP1A1/2 (7-ethoxyresorufin O-deethylase) activity revealed that maximal inhibition was observed at 96 hr of culture. HGF produced a general decrease in the activity of all the CYP isozymes studied, namely CYP1A1/2 (7-ethoxyresorufin O-deethylase), CYP2B6 (7-benzoxyresorufin O-debenzylase), CYP2A6 (coumarin 7-hydroxylase), CYP2E1 (p-nitrophenol hydroxylase) and CYP3A4 (testosterone 6beta -hydroxylase). In contrast, UDP-glucuronyltransferase and glutathione S-transferase activities and reduced glutathione levels were not modified significantly by the factor. When hepatocytes were treated with inducers, marked increases in the specific activities of CYP1A1/2 by 3-methylcholanthrene and CYP3A4 by rifampicin were observed, and these inductive effects were greatly reduced in the presence of HGF. Furthermore, CYP1A2 and CYP3A4 protein levels also dropped in the presence of HGF both in control and induced hepatocytes. The observed changes in the activity and protein levels of CYP1A2 and CYP3A4 correlated with a reduction in the specific messenger RNA levels both in control, 3-methylcholanthrene-treated (for CYP1A2) and rifampicin-treated (for CYP3A4) hepatocytes, which thus suggested that HGF could down-regulate CYP expression at a pretranslational level.

0022-3565/98/2842-0760$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
W. Lin, J. Wu, H. Dong, D. Bouck, F.-Y. Zeng, and T. Chen
Cyclin-dependent Kinase 2 Negatively Regulates Human Pregnane X Receptor-mediated CYP3A4 Gene Expression in HepG2 Liver Carcinoma Cells
J. Biol. Chem., November 7, 2008; 283(45): 30650 - 30657.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
A. E. Aitken and E. T. Morgan
Gene-Specific Effects of Inflammatory Cytokines on Cytochrome P450 2C, 2B6 and 3A4 mRNA Levels in Human Hepatocytes
Drug Metab. Dispos., September 1, 2007; 35(9): 1687 - 1693.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. E. Swales, M. Korbonits, R. Carpenter, D. T. Walsh, T. D. Warner, and D. Bishop-Bailey
The farnesoid x receptor is expressed in breast cancer and regulates apoptosis and aromatase expression.
Cancer Res., October 15, 2006; 66(20): 10120 - 10126.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
M. A. Terner, W. J. Gilmore, Y. Lou, and E. J. Squires
THE ROLE OF CYP2A AND CYP2E1 IN THE METABOLISM OF 3-METHYLINDOLE IN PRIMARY CULTURED PORCINE HEPATOCYTES
Drug Metab. Dispos., May 1, 2006; 34(5): 848 - 854.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
W. E. Thasler, R. Dayoub, M. Muhlbauer, C. Hellerbrand, T. Singer, A. Grabe, K.-W. Jauch, H.-J. Schlitt, and T. S. Weiss
Repression of Cytochrome P450 Activity in Human Hepatocytes in Vitro by a Novel Hepatotrophic Factor, Augmenter of Liver Regeneration
J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 822 - 829.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
D. Roymans, P. Annaert, J. Van Houdt, A. Weygers, J. Noukens, C. Sensenhauser, J. Silva, C. Van Looveren, J. Hendrickx, G. Mannens, et al.
EXPRESSION AND INDUCTION POTENTIAL OF CYTOCHROMES P450 IN HUMAN CRYOPRESERVED HEPATOCYTES
Drug Metab. Dispos., July 1, 2005; 33(7): 1004 - 1016.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
D. F. Balkovetz, E. R. Gerrard Jr., S. Li, D. Johnson, J. Lee, J. W. Tobias, K. K. Rogers, R. W. Snyder, and J. H. Lipschutz
Gene expression alterations during HGF-induced dedifferentiation of a renal tubular epithelial cell line (MDCK) using a novel canine DNA microarray
Am J Physiol Renal Physiol, April 1, 2004; 286(4): F702 - F710.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. Rodriguez-Antona, R. Bort, R. Jover, N. Tindberg, M. Ingelman-Sundberg, M. J. Gomez-Lechon, and J. V. Castell
Transcriptional Regulation of Human CYP3A4 Basal Expression by CCAAT Enhancer-Binding Protein alpha and Hepatocyte Nuclear Factor-3gamma
Mol. Pharmacol., May 1, 2003; 63(5): 1180 - 1189.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
M. T. Donato, P. Viitala, C. Rodriguez-Antona, A. Lindfors, J. V. Castell, H. Raunio, M. J. Gómez-Lechón, and O. Pelkonen
CYP2A5/CYP2A6 Expression in Mouse and Human Hepatocytes Treated with Various in Vivo Inducers
Drug Metab. Dispos., November 1, 2000; 28(11): 1321 - 1326.
[Abstract] [Full Text]

Home page
 Drug Metab. Dispos.Home page
W. P. Bowen, J. E. Carey, A. Miah, H. F. McMurray, P. W. Munday, R. S. James, R. A. Coleman, and A. M. Brown
Measurement of Cytochrome P450 Gene Induction in Human Hepatocytes using Quantitative Real-Time Reverse Transcriptase-Polymerase Chain Reaction
Drug Metab. Dispos., July 1, 2000; 28(7): 781 - 788.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1998 by the American Society for Pharmacology and Experimental Therapeutics.