Document Detail


Regulation of human vitamin D(3) 25-hydroxylases in dermal fibroblasts and prostate cancer LNCaP cells.
MedLine Citation:
PMID:  19286836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, we examined whether 1alpha,25-dihydroxyvitamin D(3) (calcitriol), phenobarbital, and the antiretroviral drug efavirenz, drugs used by patient groups with high incidence of low bone mineral density, could affect the 25-hydroxylase activity or expression of human 25-hydroxylases in dermal fibroblasts and prostate cancer LNCaP cells. Fibroblasts express the 25-hydroxylating enzymes CYP2R1 and CYP27A1. LNCaP cells were found to express two potential vitamin D 25-hydroxylases-CYP2R1 and CYP2J2. The presence in different cells of nuclear receptors vitamin D receptor (VDR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR) was also determined. Phenobarbital suppressed the expression of CYP2R1 in fibroblasts and CYP2J2 in LNCaP cells. Efavirenz suppressed the expression of CYP2R1 in fibroblasts but not in LNCaP cells. CYP2J2 was slightly suppressed by efavirenz, whereas CYP27A1 was not affected by any of the two drugs. Calcitriol suppressed the expression of CYP2R1 in both fibroblasts and LNCaP cells but had no clear effect on the expression of either CYP2J2 or CYP27A1. The vitamin D(3) 25-hydroxylase activity in fibroblasts was suppressed by both calcitriol and efavirenz. In LNCaP cells, consumption of substrate (1alpha-hydroxyvitamin D(3)) was used as indicator of metabolism because no 1alpha,25-dihydroxyvitamin D(3) product could be determined. The amount of 1alpha-hydroxyvitamin D(3) remaining in cells treated with calcitriol was significantly increased. Taken together, 25-hydroxylation of vitamin D(3) was suppressed by calcitriol and drugs. The present study provides new information indicating that 25-hydroxylation of vitamin D(3) may be regulated. In addition, the current results may offer a possible explanation for the impaired bone health after treatment with certain drugs.
Authors:
Maria Ellfolk; Maria Norlin; Katarina Gyllensten; Kjell Wikvall
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-13
Journal Detail:
Title:  Molecular pharmacology     Volume:  75     ISSN:  1521-0111     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-22     Completed Date:  2009-06-15     Revised Date:  2014-02-06    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1392-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / adverse effects*
Anticonvulsants / adverse effects*
Benzoxazines / adverse effects*
Calcitriol / pharmacology
Cell Line
Cell Line, Tumor
Cholestanetriol 26-Monooxygenase / biosynthesis*
Cytochrome P-450 CYP3A / biosynthesis
Cytochrome P-450 Enzyme System / biosynthesis*
Fibroblasts / drug effects*,  metabolism
Humans
Male
Phenobarbital / adverse effects*
Prostatic Neoplasms
Receptors, Calcitriol / biosynthesis
Receptors, Cytoplasmic and Nuclear / biosynthesis
Receptors, Steroid / biosynthesis
Skin / cytology
Transcription Factors / biosynthesis
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Anticonvulsants; 0/Benzoxazines; 0/Receptors, Calcitriol; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Steroid; 0/Transcription Factors; 0/constitutive androstane receptor; 0/pregnane X receptor; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.13.15/CYP27A1 protein, human; EC 1.14.13.15/CYP2R1 protein, human; EC 1.14.13.15/Cholestanetriol 26-Monooxygenase; EC 1.14.13.67/CYP3A4 protein, human; EC 1.14.14.1/Cytochrome P-450 CYP3A; EC 1.14.14.1/arachidonate epoxygenase; FXC9231JVH/Calcitriol; JE6H2O27P8/efavirenz; YQE403BP4D/Phenobarbital

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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