Linked Life Data

16885149

Source:http://linkedlifedata.com/resource/pubmed/id/16885149

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-9
pubmed:abstractText
Hypoxia inducible factor (HIF) prolyl-4-hydroxylase domain-containing proteins (PHDs) promote the degradation of HIF-1alpha. Because HIF-1alpha is highly expressed in the renal medulla and HIF-1alpha-targeted genes such as nitric oxide synthase, cyclooxygenase, and heme oxygenase are important in the regulation of renal medullary function, we hypothesized that PHD regulates HIF-1alpha levels in the renal medulla and, thereby, participates in the control of renal Na(+) excretion. Using real-time RT-PCR, Western blot, and immunohistochemical analyses, we have demonstrated that all three isoforms of PHD, PHD1, PHD2, and PHD3, are expressed in the kidneys and that PHD2 is the most abundant isoform. Regionally, all PHDs exhibited much higher levels in renal medulla than cortex. A furosemide-induced increase in renal medullary tissue Po(2) significantly decreased PHD levels in renal medulla, whereas hypoxia significantly increased mRNA levels of PHDs in cultured renal medullary interstitial cells, indicating that O(2) regulates PHDs. Functionally, the PHD inhibitor l-mimosine (l-Mim, 50 mg x kg(-1) x day(-1) i.p. for 2 wk) substantially upregulated HIF-1alpha expression in the kidneys, especially in the renal medulla, and remarkably enhanced (by >80%) the natriuretic response to renal perfusion pressure in Sprague-Dawley rats. Inhibition of HIF transcriptional activity by renal medullary transfection of HIF-1alpha decoy oligodeoxynucleotides attenuated l-Mim-induced enhancement of pressure natriuresis, which confirmed that HIF-1alpha mediated the effect of l-Mim. These results indicate that highly expressed PHDs in the renal medulla make an important contribution to the control of renal Na(+) excretion through regulation of HIF-1alpha and its targeted genes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
292
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F207-16
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed-meshheading:16885149-Animals, pubmed-meshheading:16885149-Anoxia, pubmed-meshheading:16885149-Blotting, Western, pubmed-meshheading:16885149-Cell Separation, pubmed-meshheading:16885149-Cells, Cultured, pubmed-meshheading:16885149-DNA-Binding Proteins, pubmed-meshheading:16885149-Enzyme Inhibitors, pubmed-meshheading:16885149-Furosemide, pubmed-meshheading:16885149-Heme Oxygenase-1, pubmed-meshheading:16885149-Immediate-Early Proteins, pubmed-meshheading:16885149-Immunohistochemistry, pubmed-meshheading:16885149-Kidney, pubmed-meshheading:16885149-Kidney Medulla, pubmed-meshheading:16885149-Male, pubmed-meshheading:16885149-Mimosine, pubmed-meshheading:16885149-Natriuresis, pubmed-meshheading:16885149-Osmotic Pressure, pubmed-meshheading:16885149-RNA, Messenger, pubmed-meshheading:16885149-Rats, pubmed-meshheading:16885149-Rats, Sprague-Dawley, pubmed-meshheading:16885149-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16885149-Transfection
pubmed:year
2007
pubmed:articleTitle
Expression and actions of HIF prolyl-4-hydroxylase in the rat kidneys.
pubmed:affiliation
Dept. of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth Univ., PO Box 980613, Richmond, VA 23298, USA. nli@vcu.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural