Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-7-7
pubmed:abstractText
In addition to its function as a fatty acid hydroxylase, the peroxisome proliferator-activated receptor alpha (PPARalpha) target gene, CYP4A, has been shown to be important in the conversion of arachidonic acid to the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid, suggesting a role for this enzyme in mediating vascular tone. In the present study, the cDNA sequence of beagle dog CYP4A37, CYP4A38, and CYP4A39 from the liver was determined. Open reading frame analysis predicted that CYP4A37, CYP4A38, and CYP4A39 each comprised 510 amino acids with approximately 90% sequence identity to one another, and approximately 71 and 78% sequence identity to rat CYP4A1 and human CYP4A11, respectively. PCR analysis revealed that the three dog CYP4A isoforms are expressed in kidney > liver >> lung >> intestine > skeletal muscle > heart. Treatment of primary dog hepatocytes with the PPARalpha agonists GW7647X and clofibric acid resulted in an increase in CYP4A37, CYP4A38, and CYP4A39 mRNA expression (up to fourfold), whereas HMG-CoA synthase mRNA expression was increased to a greater extent (up to 10-fold). These results suggest that dog CYP4A37, CYP4A38, and CYP4A39 are expressed in a tissue-dependent manner and that beagle dog CYP4A is not highly inducible by PPARalpha agonists, similar to the human CYP4A11 gene.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
356-67
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed-meshheading:16675513-Alkane 1-Monooxygenase, pubmed-meshheading:16675513-Animals, pubmed-meshheading:16675513-Base Sequence, pubmed-meshheading:16675513-Cell Line, pubmed-meshheading:16675513-Cercopithecus aethiops, pubmed-meshheading:16675513-Clofibric Acid, pubmed-meshheading:16675513-Cloning, Molecular, pubmed-meshheading:16675513-DNA, Complementary, pubmed-meshheading:16675513-Dogs, pubmed-meshheading:16675513-Gene Expression Regulation, Enzymologic, pubmed-meshheading:16675513-Hepatocytes, pubmed-meshheading:16675513-Humans, pubmed-meshheading:16675513-Isoenzymes, pubmed-meshheading:16675513-Kidney, pubmed-meshheading:16675513-Liver, pubmed-meshheading:16675513-Lung, pubmed-meshheading:16675513-Microsomes, Liver, pubmed-meshheading:16675513-Molecular Sequence Data, pubmed-meshheading:16675513-PPAR alpha, pubmed-meshheading:16675513-RNA, Messenger, pubmed-meshheading:16675513-Rats, pubmed-meshheading:16675513-Sequence Alignment, pubmed-meshheading:16675513-Sequence Analysis, DNA
pubmed:year
2006
pubmed:articleTitle
Cloning, tissue expression, and regulation of beagle dog CYP4A genes.
pubmed:affiliation
Division of Molecular Pharmaceutics, School of Pharmacy, The University of North Carolina at Chapel Hill, 27599, USA. richard.a.graham@gsk.com
pubmed:publicationType
Journal Article