Linked Life Data

17069767

Source:http://linkedlifedata.com/resource/pubmed/id/17069767

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-12-12
pubmed:abstractText
Proteinase-activated receptor-1 (PAR1), a thrombin receptor, plays a protective role in gastric mucosa via prostanoid formation. Thus, we studied effects of PAR1 stimulation on prostaglandin E(2) (PGE(2)) formation in rat normal gastric mucosal epithelial RGM1 cells and analyzed the underlying signal transduction mechanisms. The PAR1-activating peptide (PAR1-AP) and thrombin increased PGE(2) release from RGM1 cells for 18h, an effect being suppressed by inhibitors of COX-1, COX-2, MEK, p38 MAP kinase (p38 MAPK), protein kinase C (PKC), Src and EGF receptor-tyrosine kinase (EGFR-TK), but not JNK and matrix metalloproteinase (MMP)/a disintegrin and metalloproteinases (ADAMs). PAR1-AP caused persistent (6h or more) and transient (5min) phosphorylation of ERK and p38 MAPK, respectively, followed by delayed reinforcement at 18h. PAR1-AP up-regulated COX-2 in a manner dependent on MEK and EGFR-TK, but not p38 MAPK. The PAR1-mediated persistent ERK phosphorylation was reduced by inhibitors of Src and EGFR-TK. PAR1-AP actually phosphorylated EGF receptors and up-regulated mRNA for heparin-binding-EGF (HB-EGF), the latter effect being blocked by inhibitors of Src, EGFR-TK and MEK. Heparin, an inhibitor for HB-EGF, suppressed PAR1-mediated PGE(2) formation and persistent ERK phosphorylation. These results suggest that PAR1 up-regulates COX-2 via persistent activation of MEK/ERK that is dependent on EGFR-TK activation following induction of HB-EGF, leading to PGE(2) formation. In addition, our data also indicate involvement of COX-1, PKC and p38 MAPK in PAR1-triggered PGE(2) formation. PAR1, thus stimulates complex multiple signaling pathways responsible for PGE(2) formation in RGM1 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
103-14
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17069767-Animals, pubmed-meshheading:17069767-Base Sequence, pubmed-meshheading:17069767-Cyclooxygenase 2, pubmed-meshheading:17069767-Cyclooxygenase Inhibitors, pubmed-meshheading:17069767-DNA Primers, pubmed-meshheading:17069767-Dinoprostone, pubmed-meshheading:17069767-Epidermal Growth Factor, pubmed-meshheading:17069767-Epithelial Cells, pubmed-meshheading:17069767-Gastric Mucosa, pubmed-meshheading:17069767-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:17069767-Mitogen-Activated Protein Kinases, pubmed-meshheading:17069767-Phosphorylation, pubmed-meshheading:17069767-Rats, pubmed-meshheading:17069767-Receptor, Epidermal Growth Factor, pubmed-meshheading:17069767-Receptor, PAR-1, pubmed-meshheading:17069767-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2007
pubmed:articleTitle
Mechanisms for prostaglandin E2 formation caused by proteinase-activated receptor-1 activation in rat gastric mucosal epithelial cells.
pubmed:affiliation
Division of Physiology and Pathophysiology, School of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
pubmed:publicationType
Journal Article