Linked Life Data

18723875

Source:http://linkedlifedata.com/resource/pubmed/id/18723875

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-8-25
pubmed:abstractText
We investigated the regulation of the sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P) axis and its role during pregnancy in the rat myometrium. SphK1 and SphK2 were coexpressed in myometrium during gestation. The levels and activity of SphK1/2 were modest at midgestation (d 12), increased at d 19 and progressively declined to low at postpartum. Similar patterns were observed for the phosphorylation of ERK and protein kinase C (PKC). Inhibition of PKC and ERK reduced SphK1/2 activity. In late pregnancy, levels of cyclooxygenase 2 (COX2) increased in parallel to SphK levels. Using a pharmacological approach, we demonstrated that in primary cultures of myometrial cells from d-19 pregnant rats, induction of COX2 was mediated by 4beta-phorbol 12,13-dibutyrate and IL-1beta through sequential activation of PKC, ERK1/2, and SphK1. S1P produced by SphK1 was released in the medium. Addition of S1P, IL-1beta or 4beta-phorbol 12,13-dibutyrate enhanced COX2 levels via Gi protein. Interestingly, S1P was also released by myometrial tissues at late gestation. This event was dependent on PKC/ERK/SphK1. By contrast, in d-12 myometrial tissues, the release of S1P was markedly reduced in association with low levels of SphK1 and COX2. However, prolonged incubation of myometrium from midgestation led to the induction of COX2. This effect was blocked by SphK inhibitors, providing evidence of the close relationship between SphK activity and COX2 induction in rat myometrium. Overall, our findings provided insight into the physiological relevance of the SphK activation and S1P release in uterine smooth muscle during gestation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
149
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4669-79
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18723875-Animals, pubmed-meshheading:18723875-Cells, Cultured, pubmed-meshheading:18723875-Cyclooxygenase 2, pubmed-meshheading:18723875-Enzyme Activation, pubmed-meshheading:18723875-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:18723875-Female, pubmed-meshheading:18723875-Gestational Age, pubmed-meshheading:18723875-Lysophospholipids, pubmed-meshheading:18723875-Models, Biological, pubmed-meshheading:18723875-Myometrium, pubmed-meshheading:18723875-Phosphotransferases (Alcohol Group Acceptor), pubmed-meshheading:18723875-Postpartum Period, pubmed-meshheading:18723875-Pregnancy, pubmed-meshheading:18723875-Protein Kinase C, pubmed-meshheading:18723875-Rats, pubmed-meshheading:18723875-Rats, Wistar, pubmed-meshheading:18723875-Signal Transduction, pubmed-meshheading:18723875-Sphingosine
pubmed:year
2008
pubmed:articleTitle
Signaling pathways involved in sphingosine kinase activation and sphingosine-1-phosphate release in rat myometrium in late pregnancy: role in the induction of cyclooxygenase 2.
pubmed:affiliation
Signalisation et Régulations Cellulaires, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Unité Mixte de Recherche 8619, Centre National de la Recherche Scientifique, Batiment 430, Université Paris-Sud, 91405 Orsay, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't