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New insights into the mechanisms of vitamin D action.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2003 Mar 01; Vol. 88 (4), pp. 695-705. - Publication Year :
- 2003
-
Abstract
- The biologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is a secosteroid whose genomic mechanism of action is similar to that of other steroid hormones and is mediated by stereospecific interaction of 1,25(OH)(2)D(3) with the vitamin D receptor (VDR) which heterodimerizes with the retinoid X receptor (RXR). After interaction with the vitamin D response element (VDRE) in the promoter of target genes, transcription proceeds through the interaction of VDR with coactivators and with the transcription machinery. The identification of the steps involved in this process has been a major focus of recent research in the field. However, the functional significance of target proteins as well as the functional significance of proteins involved in the transport and metabolism of vitamin D is also of major importance. Within the past few years much new information has been obtained from studies using knockout and transgenic mice. New insight has been obtained using this technology related to the physiological significance of the vitamin D binding protein (DBP), used to transport vitamin D metabolites, as well as the physiological significance of target proteins including 25-hydroxyvitamin D(3) 24-hydroxylase (24(OH)ase), 25-hydroxyvitamin D(3)-1 alpha-hydroxylase (1 alpha-(OH)ase), VDR, and osteopontin. The crystal structure of the DBP and the ligand binding domain of the VDR have recently been reported, explaining, in part, the unique properties of these proteins. In addition novel 1,25(OH)(2)D(3) target genes have been identified including the epithelial calcium channel, present in the proximal intestine and in the distal nephron. Thus in recent years a number of exciting discoveries have been made that have enhanced our understanding of mechanisms involved in the pleiotropic actions of 1,25(OH)(2)D(3).<br /> (Copyright 2002 Wiley-Liss, Inc.)
- Subjects :
- Animals
Calcitriol genetics
Calcitriol metabolism
Calcium Channels chemistry
Calcium Channels metabolism
Cytochrome P-450 Enzyme System physiology
Histone Acetyltransferases
Immune System metabolism
Intestinal Mucosa metabolism
Kidney metabolism
Lithocholic Acid metabolism
Mice
Nuclear Receptor Coactivator 1
Osteogenesis physiology
Rats
Receptors, Calcitriol chemistry
Receptors, Calcitriol metabolism
Steroid Hydroxylases physiology
TRPV Cation Channels
Transcription Factors metabolism
Transcription, Genetic physiology
Vitamin D genetics
Vitamin D3 24-Hydroxylase
Vitamin D metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0730-2312
- Volume :
- 88
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12577303
- Full Text :
- https://doi.org/10.1002/jcb.10423