Linked Life Data

18264983

Source:http://linkedlifedata.com/resource/pubmed/id/18264983

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-4-29
pubmed:abstractText
Bradykinin (BK) represents a pro-inflammatory mediator that partakes in many inflammatory diseases. The mechanism of action of BK is thought to be primarily mediated by specific cell surface membrane B2 receptors (B2Rs). Some evidence has suggested, however, the existence of an intracellular/nuclear B2R population. Whether these receptors are functional and contribute to BK signaling remains to be determined. In this study, by mean of Western blotting, 3D-confocal microscopy, receptor autoradiography and radioligand binding analysis, we showed that plasma membrane and highly purified nuclei from isolated rat hepatocytes contain specific B2R that bind BK. The results depicting B2R nuclear expression in isolated nuclear organelles were reproduced in situ on hepatic sections by immunogold labeling and transmission electron microscopy. Functional tests on single nuclei, by means of confocal microscopy and the calcium-sensitive probe fluo-4AM, showed that BK induces concentration-dependent transitory mobilization of nucleoplasmic calcium; these responses were blocked by B2R antagonist HOE 140, not by the B1R antagonist R954 and, were also found in wild-type C57/Bl6 mice, but not in B2R-KO mice. In isolated nuclei, BK elicited activation/phosphorylation of Akt, acetylation of histone H3 and ensuing pro-inflammatory iNOS gene induction as determined by Western blot and RT-PCR. ChIP assay confirmed binding of acetylated-histone H3 complexes, but not B2R, to promoter region of iNOS gene suggesting that B2R-mediated gene expression is bridged with accessory downstream effectors. This study discloses a previously undescribed mechanism in BK-induced transcriptional events, via intracrine B2R-mediated signaling, occurring in rat autologous hepatic cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1097-4652
pubmed:author
pubmed:copyrightInfo
(c) 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
216
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
234-44
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18264983-Animals, pubmed-meshheading:18264983-Bradykinin, pubmed-meshheading:18264983-Cell Membrane, pubmed-meshheading:18264983-Cell Nucleus, pubmed-meshheading:18264983-Gene Expression Regulation, pubmed-meshheading:18264983-Genes, Immediate-Early, pubmed-meshheading:18264983-Hepatocytes, pubmed-meshheading:18264983-Humans, pubmed-meshheading:18264983-Kininogen, High-Molecular-Weight, pubmed-meshheading:18264983-Kininogen, Low-Molecular-Weight, pubmed-meshheading:18264983-Male, pubmed-meshheading:18264983-Mice, pubmed-meshheading:18264983-Mice, Inbred C57BL, pubmed-meshheading:18264983-Mice, Knockout, pubmed-meshheading:18264983-Nitric Oxide Synthase Type II, pubmed-meshheading:18264983-Phosphatidylinositol 3-Kinases, pubmed-meshheading:18264983-Proto-Oncogene Proteins c-akt, pubmed-meshheading:18264983-Radioligand Assay, pubmed-meshheading:18264983-Rats, pubmed-meshheading:18264983-Rats, Sprague-Dawley, pubmed-meshheading:18264983-Receptor, Bradykinin B2, pubmed-meshheading:18264983-Signal Transduction, pubmed-meshheading:18264983-Transcriptional Activation, pubmed-meshheading:18264983-Vasodilator Agents
pubmed:year
2008
pubmed:articleTitle
Expression of endogenous nuclear bradykinin B2 receptors mediating signaling in immediate early gene activation.
pubmed:affiliation
Department of Pharmacology, Université de Sherbrooke, Sherbrooke, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't