Regulation of 24,25-dihydroxyvitamin D-3 production by 1,25-dihydroxyvitamin D-3 and synthetic human parathyroid hormone fragment 1–34 in a cloned monkey kidney cell line (JTC-12)

Matsumoto, Toshio; Kawanobe, Yumiko; Ogata, Etsuro

doi:10.1016/0167-4889(85)90199-5

Cited by 33 publications

(7 citation statements)

References 17 publications

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“…Both cell lines express endogenous VDR and respond to 1,25-(OH) 2 D 3 -mediated gene induction (38,42). Expression of the wild-type and mutant CYP24 promoter constructs in JTC-12 and ROS 17/2.8 cells produced transactivation results that were similar to those obtained in COS-1 cells (Fig.…”

Section: Vdre-1: 5ј-tcgagcggcgccctcactcacctcgcg-3јsupporting

confidence: 70%

Transcriptional Synergism between Vitamin D-responsive Elements in the Rat 25-Hydroxyvitamin D3 24-Hydroxylase (CYP24) Promoter

Kerry

Dwivedi

Hahn

et al. 1996

Journal of Biological Chemistry

115

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The hormone 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 1 or calcitriol) is a pleiotropic secosteroid that functions in the regulation of calcium homeostasis, cellular differentiation and proliferation, and immune function (1-5). Nuclear actions of 1,25-(OH) 2 D 3 involve the transcriptional regulation of gene expression, which is mediated by the vitamin D receptor (VDR), a ligand-activated transcription factor that belongs to the nuclear receptor superfamily (1, 6 -10). Activated VDR can bind as either a homodimer or a heterodimeric complex to a DNA sequence known as the vitamin D-responsive element (VDRE) present in the promoter of target genes (11-13). Heterodimers consisting of VDR and retinoid X receptor (RXR) are widely documented (12), although VDR heterodimeric complexes have also been demonstrated for both the retinoic acid receptor (14, 15) and the thyroid hormone receptor (16). Vitamin D-responsive elements generally display a binding motif that consists of two imperfect, direct repeat hexameric sequences (i.e. halfsites) that are separated by 3 bp or, more rarely, by 6 bp; these VDREs are referred to as DR-3 and DR-6, respectively (12).Metabolic inactivation of 1,25-(OH) 2 D 3 and conversion to water-soluble calcitroic acid occurs through the C-24 oxidation pathway. The initial step in this pathway involves the 24-hydroxylation of 1,25-(OH) 2 D 3 by the mitochondrial enzyme 25-hydroxyvitamin D 3 24-hydroxylase (CYP24) (17, 18). Rats fed a normal diet express a low level of CYP24, predominantly in the kidney. However, the enzyme can be substantially induced in kidney and intestine (19 -23) and various other cells (24 -29) by 1,25-(OH) 2 D 3 treatment. Up-regulation of CYP24 expression (19 -23) increases the metabolic clearance of 1,25-(OH) 2 D 3 , and, thereby, feedback regulates the hormone's ambient and cellular levels (17, 18). The mechanism whereby 1,25-(OH) 2 D 3 acts to modulate cellular CYP24 expression is of fundamental importance to understanding the hormone's role in health and disease.Molecular regulatory studies of CYP24 gene expression by 1,25-(OH) 2 D 3 are in progress and promoter analysis data for rat (14, 30 -33) and human (34) have been reported. In the rat CYP24 gene promoter, three VDREs on the antisense strand have been identified. We have previously defined the proximal VDRE (30) in its native promoter context, while the two more distal VDREs have been tested by fusing to a heterologous promoter (14, 31). To date, however, the functionality of the VDREs has not been verified in the context of the native CYP24 promoter, and there is no direct information available regarding the contribution of each VDRE to vitamin D induction or whether there is a cooperative interaction between the response elements. These issues are addressed in the current investigation, in which mutagenic constructs of the rat CYP24 promoter have been used in transient gene expression and gel mobility shift analysis. Construction of Mutant Clones-A 365-bp PvuII/StuI fragment containing 298 bp of 5Ј-flanking se...

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Section: Vdre-1: 5ј-tcgagcggcgccctcactcacctcgcg-3јsupporting

confidence: 70%

Transcriptional Synergism between Vitamin D-responsive Elements in the Rat 25-Hydroxyvitamin D3 24-Hydroxylase (CYP24) Promoter

Kerry

Dwivedi

Hahn

et al. 1996

Journal of Biological Chemistry

115

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“…In response to hypocalcemia, PTH strongly induces CYP27B1 activity [4] and inhibits CYP24 activity [5,6]. In response to hypercalcemia, calcitonin suppresses calcium resorption in bone [7].…”

Section: Introductionmentioning

confidence: 98%

Determinants of circulating 1,25-dihydroxyvitamin D3 levels: the role of renal synthesis and catabolism of vitamin D

Anderson¹,

O’Loughlin²,

May³

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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“…24-hydroxylase enzyme activity and mRNA expression in the kidney is up-regulated by 1α,25(OH) 2 D 3 [128–134]. The effect of 1α,25(OH) 2 D 3 is blunted in vitro and in vivo by parathyroid hormone [128–131]. We used antibodies against the 24-hydroxylase cytochrome P-450 to examine the distribution of the enzyme in the human kidney, and found high concentrations of the cytochrome P-450 in distal tubular cells and lower amounts in the proximal tubule [11].…”

Section: Role Of the Kidney In The Metabolism Of 25oh Dmentioning

confidence: 99%

Vitamin D and the kidney

Kumar¹,

Tebben²,

Thompson³

2012

Archives of Biochemistry and Biophysics

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Regulation of 24,25-dihydroxyvitamin D-3 production by 1,25-dihydroxyvitamin D-3 and synthetic human parathyroid hormone fragment 1–34 in a cloned monkey kidney cell line (JTC-12)

Cited by 33 publications

References 17 publications

Transcriptional Synergism between Vitamin D-responsive Elements in the Rat 25-Hydroxyvitamin D3 24-Hydroxylase (CYP24) Promoter

Transcriptional Synergism between Vitamin D-responsive Elements in the Rat 25-Hydroxyvitamin D3 24-Hydroxylase (CYP24) Promoter

Determinants of circulating 1,25-dihydroxyvitamin D3 levels: the role of renal synthesis and catabolism of vitamin D

Vitamin D and the kidney

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