Linked Life Data

20430864

Source:http://linkedlifedata.com/resource/pubmed/id/20430864

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-7-15
pubmed:abstractText
We demonstrated recently that cytochrome b(5) plays an important in vivo role in hepatic cytochrome P450 (P450) function [J Biol Chem 283:31385-31393, 2008]. We have now generated a model in which cytochrome b(5) has been deleted in all tissues [cytochrome b(5) complete null (BCN)], which surprisingly results in a viable mouse despite the putative in vivo roles of this protein in lipid and steroid hormone metabolism and the reduction of methemoglobin. In contrast to the liver-specific deletion, complete deletion of cytochrome b(5) leads to a neonatal increase in the expression of many hepatic P450s at both the protein and mRNA level. In extrahepatic tissues, some changes in P450 expression were also observed that were isoform-dependent. In vitro cytochrome P450 activities in liver, kidney, lung, and small intestine of BCN mice were determined for a range of model substrates and probe drugs; a profound reduction in the metabolism of some substrates, particularly in lung, kidney, and small intestine, was observed. In vivo, the metabolism of metoprolol was significantly altered in BCN mice, in contrast to the previous finding in the liver-specific cytochrome b(5) deletion, suggesting that extrahepatic cytochrome b(5) plays a significant role in its disposition. Testicular Cyp17 hydroxylase and lyase activities were also significantly reduced by cytochrome b(5) deletion, leading to significantly lower levels of testicular testosterone. The BCN mouse provides an additional model system with which to further investigate the functions of cytochrome b(5), particularly in extrahepatic tissues.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
269-78
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Deletion of microsomal cytochrome b5 profoundly affects hepatic and extrahepatic drug metabolism.
pubmed:affiliation
Cancer Research UK Molecular Pharmacology Unit, Biomedical Research Institute, Ninewells Hospital & Medical School, Dundee, United Kingdom .
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't