Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-10-2
pubmed:abstractText
The CYP4A enzymes catalyze the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), which has potent effects on the renal vasculature and tubular ion transport. Based on an increased 20-HETE formation in renal microsomes from spontaneously hypertensive rats, it has been proposed that increased expression of the CYP4A genes is an early event in the development of hypertension in these animals. To test this hypothesis, we developed RNase protection assays for specific detection of the individual CYP4A genes in the kidneys of spontaneously hypertensive and Wistar-Kyoto rats. Distinct age-dependent patterns of expression were observed for the individual CYP4A genes, with only CYP4A3 mRNA measurable in the kidneys of 1-week-old rats. CYP4A1 and CYP4A8 mRNA were detectable by 3 weeks of age and CYP4A2 mRNA at 5 weeks of age. The expression of CYP4A1 and CYP4A3 varied 4-5-fold throughout development and was highest between 3 and 5 weeks of age, declining steadily thereafter to 20% of their maximal level by 9 weeks of age. CYP4A2 mRNA levels increased steadily between 5 and 9 weeks of age, whereas CYP4A8 mRNA levels were relatively constant throughout development. The CYP4A3 mRNA level was significantly increased 1. 6-2-fold in the cortex and outer medulla of 1-4-week-old spontaneously hypertensive rat kidneys relative to the corresponding level in the Wistar-Kyoto. A similar 1.4-1.7-fold increase in CYP4A8 mRNA was also found in 3- and 4-week-old spontaneously hypertensive kidneys. Accompanying the increased expression of CYP4A3 and CYP4A8 mRNA in the prehypertensive rats were corresponding changes in functional CYP4A measured as either arachidonic acid or lauric acid omega-hydroxylase activity (1.4-2.0-fold increases) and CYP4A protein levels. After 4 weeks of age, the level of CYP4A mRNA, enzyme activity, and protein were similar in the kidneys of Wistar-Kyoto and spontaneously hypertensive rats. The findings suggest that the expression of CYP4A3 and CYP4A8 may be critical to the early changes in eicosanoid formation and renal function in the young spontaneously hypertensive rat.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
362-72
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9281597-Alkane 1-Monooxygenase, pubmed-meshheading:9281597-Animals, pubmed-meshheading:9281597-Arachidonic Acid, pubmed-meshheading:9281597-Blood Pressure, pubmed-meshheading:9281597-Cytochrome P-450 Enzyme System, pubmed-meshheading:9281597-Gene Expression Regulation, Developmental, pubmed-meshheading:9281597-Gene Expression Regulation, Enzymologic, pubmed-meshheading:9281597-Hydroxyeicosatetraenoic Acids, pubmed-meshheading:9281597-Hypertension, Renal, pubmed-meshheading:9281597-Kidney, pubmed-meshheading:9281597-Lauric Acids, pubmed-meshheading:9281597-Male, pubmed-meshheading:9281597-Mixed Function Oxygenases, pubmed-meshheading:9281597-RNA, Messenger, pubmed-meshheading:9281597-Rats, pubmed-meshheading:9281597-Rats, Inbred SHR, pubmed-meshheading:9281597-Rats, Inbred WKY, pubmed-meshheading:9281597-Ribonucleases
pubmed:year
1997
pubmed:articleTitle
Developmentally regulated expression of the CYP4A genes in the spontaneously hypertensive rat kidney.
pubmed:affiliation
Department of Biopharmaceutical Sciences, University of California San Francisco, San Francisco, California 94122, USA. deana@itsa.ucsf.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't