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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
37
|
| pubmed:dateCreated |
1994-10-11
|
| pubmed:abstractText |
Prostaglandin G/H synthase (PGHS) is one of the key enzymes in prostaglandin synthesis. Regulation of the mRNA expression of the two isozymes PGHS-1 and PGHS-2 was investigated in mesangial cells. PGHS-1 was constitutively expressed and not modulated by any of the stimuli used. PGHS-2 was induced by the platelet products serotonin (5-HT) and thromboxane A2 (used as its analogue U46619), but not by ATP. Expression of PGHS protein was regulated correspondingly; whereas PGHS-1 protein was constitutively expressed, PGHS-2 protein was virtually absent in unstimulated cells, but could increasingly be induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), 5-HT, or fetal calf serum. Induction of PGHS-2 mRNA was transient with a peak after 2-3 h. Stimulated mRNA levels persisted for more than 6 h when transcription was inhibited by actinomycin D or when translation was inhibited by cycloheximide. As shown by specific inhibitors, 5-HT signal transduction was mediated by 5-HT2 receptors, which couple to phospholipase C via pertussis toxin-sensitive G-proteins. Induction of PGHS-2 mRNA by 5-HT was dependent on protein kinase C. Down-regulation of the enzyme by prolonged incubation with TPA abolished 5-HT-induced PGHS-2 mRNA expression. Short time activation of protein kinase C by TPA induced PGHS-2 mRNA expression. On the other hand, TPA given immediately before 5-HT decreased the 5-HT-induced PGHS-2 mRNA expression, indicating a negative feedback. The immunosuppressive drug cyclosporin A reduced induction of PGHS-2 mRNA expression by 5-HT, indicating interference with the signaling cascade, most likely with the Ser/Thr phosphatase calcineurin. Involvement of Tyr phosphorylation in 5-HT signaling was shown by the Tyr kinase inhibitor genistein, which inhibited the induction, while the Tyr phosphatase inhibitor vanadate by itself was able to induce PGHS-2 mRNA expression, which was further augmented when vanadate was combined with 5-HT. PGHS-2 mRNA expression is thus tightly regulated in mesangial cells and therefore allows modulation at various levels by physiological and pharmacological stimuli.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/15-Hydroxy-11 alpha,9...,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin Endoperoxides...,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Thromboxane A2,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
16
|
| pubmed:volume |
269
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
22952-7
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8083194-15-Hydroxy-11 alpha,9...,
pubmed-meshheading:8083194-Adenosine Triphosphate,
pubmed-meshheading:8083194-Animals,
pubmed-meshheading:8083194-Base Sequence,
pubmed-meshheading:8083194-Cycloheximide,
pubmed-meshheading:8083194-DNA Primers,
pubmed-meshheading:8083194-Dactinomycin,
pubmed-meshheading:8083194-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:8083194-Glomerular Mesangium,
pubmed-meshheading:8083194-Isoenzymes,
pubmed-meshheading:8083194-Molecular Sequence Data,
pubmed-meshheading:8083194-Phosphorylation,
pubmed-meshheading:8083194-Prostaglandin Endoperoxides, Synthetic,
pubmed-meshheading:8083194-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:8083194-Protein Kinase C,
pubmed-meshheading:8083194-RNA, Messenger,
pubmed-meshheading:8083194-Rats,
pubmed-meshheading:8083194-Serotonin,
pubmed-meshheading:8083194-Signal Transduction,
pubmed-meshheading:8083194-Thromboxane A2,
pubmed-meshheading:8083194-Thymidine
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
Signal transduction pathways responsible for serotonin-mediated prostaglandin G/H synthase expression in rat mesangial cells.
|
| pubmed:affiliation |
Department of Medicine IV, University of Erlangen-Nuernberg, Federal Republic of Germany.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|