Linked Life Data

20622109

Source:http://linkedlifedata.com/resource/pubmed/id/20622109

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-8-31
pubmed:abstractText
Atherosclerosis is a chronic inflammation disease characterized by acidic micromilieu and the accumulation of numerous bioactive lipid mediators, such as lysophosphatidic acid (LPA) and prostaglandins, in the atherosclerotic lesion. Chronic acidification induced various effects on vascular smooth muscle cells, but the molecular mechanisms underlying these effects remain unknown. In this study, we examine the role of proton-sensing ovarian cancer G protein-coupled receptor 1 (OGR1) in extracellular acidification-induced regulation of cyclooxygenase (COX)-2 induction, PGI(2) production, MAPK phosphatase (MKP)-1 expression, and plasminogen activator inhibitor (PAI)-1 expression and proliferation in human aortic smooth muscle cells (AoSMCs). Experiments with knockdown with small interfering RNA specific to OGR1 and specific inhibitors for G proteins showed that acidification-induced COX-2 expression, PGI(2) production, and MKP-1 expression, but not PAI-1 expression and inhibition of proliferation, were dependent on OGR1 and mainly mediated by G(q/11) protein. LPA remarkably enhanced, through the LPA(1) receptor/G(i) protein, the OGR1-mediated vascular actions to acidic pH. In conclusion, acidic pH-induced vascular actions of AoSMCs can be dissected to OGR1-dependent and -independent pathways: COX-2 expression, PGI(2) production, and MKP-1 expression are mediated by OGR1, but PAI-1 expression and inhibition of proliferation are not. LPA, which is usually thought to be a proatherogenic lipid mediator, may exert antiatherogenic actions under acidic micromilieu through cross-talk between LPA(1)/G(i) protein and OGR1/G(q/11) protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H731-42
pubmed:meshHeading
pubmed-meshheading:20622109-Analysis of Variance, pubmed-meshheading:20622109-Aorta, pubmed-meshheading:20622109-Blotting, Western, pubmed-meshheading:20622109-Cells, Cultured, pubmed-meshheading:20622109-Cyclic AMP, pubmed-meshheading:20622109-Cyclooxygenase 2, pubmed-meshheading:20622109-Dual Specificity Phosphatase 1, pubmed-meshheading:20622109-Epoprostenol, pubmed-meshheading:20622109-Humans, pubmed-meshheading:20622109-Hydrogen-Ion Concentration, pubmed-meshheading:20622109-Muscle, Smooth, Vascular, pubmed-meshheading:20622109-Myocytes, Smooth Muscle, pubmed-meshheading:20622109-Plasminogen Activator Inhibitor 1, pubmed-meshheading:20622109-Receptors, G-Protein-Coupled, pubmed-meshheading:20622109-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20622109-Transfection
pubmed:year
2010
pubmed:articleTitle
Ovarian cancer G protein-coupled receptor 1-dependent and -independent vascular actions to acidic pH in human aortic smooth muscle cells.
pubmed:affiliation
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't