Linked Life Data

18469514

Source:http://linkedlifedata.com/resource/pubmed/id/18469514

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-6-23
pubmed:abstractText
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by a progressive mineralization of connective tissue, resulting in skin, arterial and eye disease. Classical PXE is caused by mutations in the ABCC6 gene, which encodes a member of the ABCC (MRP) family of organic anion transporters. Recent studies on Abcc6(-/-) mice show that the absence of ABCC6 in the liver is crucial for PXE and confirm the "metabolic disease hypothesis" for PXE, which states that tissue calcification is due to the absence of a plasma factor secreted from the basolateral hepatocyte membrane. We propose that this plasma factor is vitamin K (precursor). We propose that vitamin K (precursor) is secreted by ABCC6 from the liver as a glutathione--(or glucuronide)--conjugate and that this supplements the vitamin K need of peripheral tissues that receive insufficient vitamin from the diet, because dietary vitamin K is effectively extracted from blood by the liver. Peripheral tissue vitamin K is needed for the gamma-carboxylation of glutamate residues in proteins known to be required for counteracting calcification of connective tissue throughout the body. Our hypothesis explains the known facts of PXE and also explains why PXE-like symptoms can occur in patients with mutations in the gamma-glutamyl carboxylase gene (encoding the enzyme responsible for protein carboxylase) and in rats treated with vitamin K antagonists. The hypothesis implies that the symptoms of PXE can be prevented or mitigated by providing patients (intravenously) with a form of plasma vitamin K (precursor) that can be used by peripheral tissues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1575-9
pubmed:dateRevised
2008-10-8
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Does the absence of ABCC6 (multidrug resistance protein 6) in patients with Pseudoxanthoma elasticum prevent the liver from providing sufficient vitamin K to the periphery?
pubmed:affiliation
The Netherlands Cancer Institute, Division of Molecular Biology, Amsterdam, The Netherlands. p.borst@nki.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't