Linked Life Data

10364221

Source:http://linkedlifedata.com/resource/pubmed/id/10364221

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
1999-7-15
pubmed:databankReference
pubmed:abstractText
A cDNA encoding a new cytochrome P450 was isolated from a mouse liver library. Sequence analysis reveals that this 1,886-base pair cDNA encodes a 501-amino acid polypeptide that is 69-74% identical to CYP2J subfamily P450s and is designated CYP2J5. Recombinant CYP2J5 was co-expressed with NADPH-cytochrome P450 oxidoreductase in Sf9 cells using a baculovirus system. Microsomal fractions of CYP2J5/NADPH-cytochrome P450 oxidoreductase-transfected cells metabolize arachidonic acid to 14,15-, 11,12-, and 8, 9-epoxyeicosatrienoic acids and 11- and 15-hydroxyeicosatetraenoic acids (catalytic turnover, 4.5 nmol of product/nmol of cytochrome P450/min at 37 degrees C); thus CYP2J5 is enzymologically distinct. Northern analysis reveals that CYP2J5 transcripts are most abundant in mouse kidney and present at lower levels in liver. Immunoblotting using a polyclonal antibody against a CYP2J5-specific peptide detects a protein with the same electrophoretic mobility as recombinant CYP2J5 most abundantly in mouse kidney microsomes. CYP2J5 is regulated during development in a tissue-specific fashion. In the kidney, CYP2J5 is present before birth and reaches maximal levels at 2-4 weeks of age. In the liver, CYP2J5 is absent prenatally and during the early postnatal period, first appears at 1 week, and then remains relatively constant. Immunohistochemical staining of kidney sections with anti-human CYP2J2 IgG reveals that CYP2J protein(s) are present primarily in the proximal tubules and collecting ducts, sites where the epoxyeicosatrienoic acids are known to modulate fluid/electrolyte transport and mediate hormonal action. In situ hybridization confirms abundant CYP2J5 mRNA within tubules of the renal cortex and outer medulla. Epoxyeicosatrienoic acids are endogenous constituents of mouse kidney thus providing direct evidence for the in vivo metabolism of arachidonic acid by the mouse renal epoxygenase(s). Based on these data, we conclude that CYP2J5 is an enzymologically distinct, developmentally regulated, protein that is localized to specific nephron segments and contributes to the oxidation of endogenous renal arachidonic acid pools. In light of the well documented effects of epoxyeicosatrienoic acids in modulating renal tubular transport processes, we postulate that CYP2J5 products play important functional roles in the kidney.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17777-88
pubmed:dateRevised
2009-9-28
pubmed:meshHeading
pubmed-meshheading:10364221-Amino Acid Sequence, pubmed-meshheading:10364221-Animals, pubmed-meshheading:10364221-Arachidonic Acid, pubmed-meshheading:10364221-Base Sequence, pubmed-meshheading:10364221-Cloning, Molecular, pubmed-meshheading:10364221-Cytochrome P-450 Enzyme System, pubmed-meshheading:10364221-Eicosanoids, pubmed-meshheading:10364221-Epoxy Compounds, pubmed-meshheading:10364221-Gene Expression Regulation, Developmental, pubmed-meshheading:10364221-Humans, pubmed-meshheading:10364221-Immunohistochemistry, pubmed-meshheading:10364221-In Situ Hybridization, pubmed-meshheading:10364221-Kidney, pubmed-meshheading:10364221-Kinetics, pubmed-meshheading:10364221-Mice, pubmed-meshheading:10364221-Molecular Sequence Data, pubmed-meshheading:10364221-NADH, NADPH Oxidoreductases, pubmed-meshheading:10364221-NADPH-Ferrihemoprotein Reductase, pubmed-meshheading:10364221-RNA, Messenger, pubmed-meshheading:10364221-Rats, pubmed-meshheading:10364221-Recombinant Proteins
pubmed:year
1999
pubmed:articleTitle
Molecular cloning, enzymatic characterization, developmental expression, and cellular localization of a mouse cytochrome P450 highly expressed in kidney.
pubmed:affiliation
Laboratories of Pulmonary Pathobiology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.