Source:http://linkedlifedata.com/resource/pubmed/id/15872077
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2005-6-29
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| pubmed:abstractText |
PDGF and nitric oxide (NO) have been shown to participate in the progression of several forms of glomerulonephritis. A potential influence of NO on PDGF-mediated signaling cascades was therefore examined. Treatment of rat mesangial cells (MC) with the NO donors diethylenetriamine NO (DETA-NO) or spermine-NONOate resulted in a time- and dose-dependent upregulation of PDGF receptor alpha (PDGFRalpha) but not PDGFRbeta mRNA levels. Administration of DETA-NO also induced PDGFRalpha protein expression that was paralleled also by an enhanced receptor phosphorylation. Further experiments using 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole (YC-1), an activator of the soluble guanylyl cyclase (sGC), the membrane-soluble cyclic GMP (cGMP) analog 8-Bromo-PET-cGMP, and the inhibitors of sGC ODQ and NS2028 suggest that elevated cGMP levels are responsible for the effects of NO. Importantly, NO-dependent autophosphorylation of PDGFRalpha drastically augmented PDGF-AA-evoked phosphorylation of PKB/Akt, a classical downstream target of PDGFRalpha signaling. Furthermore, in a rat model of anti-Thy-1 glomerulonephritis, expression and phosphorylation of PDGFRalpha but not PDGFRbeta expression was markedly reduced in nephritic animals that were treated with the inducible NO synthase inhibitor L-N6(1-iminoethyl)lysine(dihydrochloride) (L-NIL) compared with non-L-NIL-treated nephritic rats as demonstrated by Western blotting and immunohistochemistry. Taken together, the data suggest that NO modulates PDGFRalpha-triggered signaling in a cGMP-dependent manner by induction of PDGFRalpha expression in MC and in a rat model of mesangioproliferative glomerulonephritis. The mechanistic details of this regulation have to be elucidated in further experiments.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
|
| pubmed:issn |
1046-6673
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| pubmed:author |
pubmed-author:BabelovaAndreaA,
pubmed-author:BeckKarl-FriedrichKF,
pubmed-author:BeckMartinaM,
pubmed-author:BehrensMeik HMH,
pubmed-author:GüderGülmisalG,
pubmed-author:MihalikDanielD,
pubmed-author:PfeilschifterJosefJ,
pubmed-author:PleskovaMiriamM,
pubmed-author:SchaeferLilianaL,
pubmed-author:SchaeferRoland MRM
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| pubmed:issnType |
Print
|
| pubmed:volume |
16
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1948-57
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:15872077-Animals,
pubmed-meshheading:15872077-Cells, Cultured,
pubmed-meshheading:15872077-Glomerular Mesangium,
pubmed-meshheading:15872077-Glomerulonephritis,
pubmed-meshheading:15872077-Isoantibodies,
pubmed-meshheading:15872077-Models, Animal,
pubmed-meshheading:15872077-Nitric Oxide,
pubmed-meshheading:15872077-Rats,
pubmed-meshheading:15872077-Receptor, Platelet-Derived Growth Factor alpha,
pubmed-meshheading:15872077-Up-Regulation
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| pubmed:year |
2005
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| pubmed:articleTitle |
Nitric oxide upregulates induction of PDGF receptor-alpha expression in rat renal mesangial cells and in anti-Thy-1 glomerulonephritis.
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| pubmed:affiliation |
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe Universität Frankfurt am Main, Theodor-Stern-Kai 7, D-60590, Frankfurt am Main, Germany. k.f.beck@em.uni-frankfurt.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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