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Rapid and drastic induction of CYP3A4 mRNA expression via vitamin D receptor in human intestinal LS180 cells.
- Source :
-
Drug metabolism and pharmacokinetics [Drug Metab Pharmacokinet] 2007 Oct; Vol. 22 (5), pp. 377-81. - Publication Year :
- 2007
-
Abstract
- The aim of this study was to evaluate the usefulness of human intestinal LS180 cells for studying the induction of CYP3A4 mRNA expression via vitamin D receptor (VDR). CYP3A4 mRNA expression in LS180 cells treated with 100 nM 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) for 6 and 24 h was approximately 80- and 500-fold higher than the control, respectively. A protein kinase (PK) inhibitor (staurosporine), c-jun N-terminal kinase (JNK) pathway inhibitor (curcumin), and JNK inhibitor (SP600125) attenuated 1alpha,25(OH)(2)D(3)-induced CYP3A4 mRNA expression, suggesting that the PK-JNK pathway contributed to the rapid and drastic induction of CYP3A4 expression via VDR in LS180 cells. The ability of CYP3A4 mRNA induction in LS180 cells was highly dependent on the site and number of vitamin D(3) and D(2) hydroxylation. In addition, short-time (6 h) treatment of LS180 cells with cytotoxic secondary bile acids, lithocholic acid (LCA) and 3-keto-LCA also significantly induced the mRNA expression of CYP3A4. LS180 cells may be useful to quickly investigate the CYP3A4-inducing effect of drugs, xenobiotics, and/or endogenous substrates in the intestinal epithelia.
- Subjects :
- Anthracenes pharmacology
Calcitriol metabolism
Cell Line
Curcumin pharmacology
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System genetics
Enzyme Induction
Humans
Hydroxylation
Intestinal Mucosa drug effects
Intestinal Mucosa enzymology
JNK Mitogen-Activated Protein Kinases antagonists & inhibitors
JNK Mitogen-Activated Protein Kinases metabolism
Lithocholic Acid analogs & derivatives
Lithocholic Acid metabolism
Molecular Structure
Protein Kinase Inhibitors pharmacology
Staurosporine pharmacology
Time Factors
Vitamin D analogs & derivatives
Vitamin D chemistry
Cytochrome P-450 Enzyme System biosynthesis
Intestinal Mucosa metabolism
RNA, Messenger biosynthesis
Receptors, Calcitriol metabolism
Vitamin D metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1347-4367
- Volume :
- 22
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Drug metabolism and pharmacokinetics
- Publication Type :
- Academic Journal
- Accession number :
- 17965521
- Full Text :
- https://doi.org/10.2133/dmpk.22.377