Linked Life Data

20619365

Source:http://linkedlifedata.com/resource/pubmed/id/20619365

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-11-26
pubmed:abstractText
From earliest development on, the vitamin D receptor (VDR) is expressed in most cells of the mammalian body. The VDR is a nuclear, ligand-induced transcription factor that regulates in complex with hormonally active vitamin D the expression of more than 900 genes involved in a wide array of physiological functions (e.g. calcium homeostasis, growth control, differentiation, cognition, immune response, etc.). Accordingly, severe health problems are associated to vitamin deficiencies. Synthesis of the major active form 1?,25(OH)?D? from vitamin D and subsequent metabolism are exclusively controlled by specific P450-forms. Synthesis, a two-step process, starts with a 25-hydroxylation primarily by CYP2R1 (CYP27A1, CYP2J2, and CYP3A4 may also contribute) and a subsequent 1?-hydroxylation via CYP27B1. Circulating in the bloodstream, 1?,25(OH)?D? acts at sites of VDR expression (target sites) in an endocrine way. However, it is also capable of autocrine/paracrine functions since various target tissues are fully competent in 1?,25(OH)?D? synthesis, as illustrated by three examples. 1?,25(OH)?D? levels are short-lived: the hormone upregulates its rapid metabolism by CYP24A1 that attacks repeatedly the vitamin D C????? side chain, thereby producing a complex cascade of transient metabolites with increasing polarity. Most of these metabolites still retain 1?,25(OH)?D?-like activities on the VDR, contributing to the overall effect that is commonly attributed to 1?,25(OH)?D?. As selective inhibitors of CYP24A1 increase the lifetime and thereby the function of vitamin D metabolites, they will help exploring whether and which intrinsic activities distinct metabolites possess. It appears likely that this strategy may unmask important regulators of new functions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-3002
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:volume
1814
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
186-99
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Cytochromes P450 are essential players in the vitamin D signaling system.
pubmed:affiliation
Department of Theoretical Chemistry, University of Vienna, Währingerstraße 17, A 1090 Wien, Austria. inge@tbi.univie.ac.at
pubmed:publicationType
Journal Article, Review