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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1998-1-15
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pubmed:abstractText |
Tetrahydrobiopterin (BH4) biosynthetic pathways are stimulated under inflammatory conditions. The newly synthesized BH4 serves as a cofactor for optimal activity of inducible nitric oxide synthase (NOS2). In human mesangial cells (HMC), BH4 is also a limiting factor for NOS2 expression. In this study we show that BH4 availability can also play a modulatory role in the expression of cyclooxygenase 2 (COX-2) in HMC. Supplementing HMC with the BH4 donor sepiapterin potentiated IL-1beta/TNF-alpha-induced COX-2 expression by approximately 2-fold. This effect was abolished by methotrexate. In contrast, the NOS inhibitor L-NAME and the soluble guanylate cyclase inhibitor ODQ did not block sepiapterin amplification of COX-2 expression. Moreover, sepiapterin was found to modulate the tyrosine phosphorylation of several cellular substrates, an early event which occurred well before the induction of NOS2 could be evidenced. These findings suggest a role for BH4 in the modulation of mesangial cell responses to pro-inflammatory stimuli.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1H-(1,2,4)oxadiazolo(4,3-a)quinoxali...,
http://linkedlifedata.com/resource/pubmed/chemical/5,6,7,8-tetrahydrobiopterin,
http://linkedlifedata.com/resource/pubmed/chemical/Biopterin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Methotrexate,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Oxadiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Pteridines,
http://linkedlifedata.com/resource/pubmed/chemical/Pterins,
http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/sepiapterin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 1997 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
241
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7-12
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9405225-Biopterin,
pubmed-meshheading:9405225-Cells, Cultured,
pubmed-meshheading:9405225-Cyclooxygenase 2,
pubmed-meshheading:9405225-Dinoprostone,
pubmed-meshheading:9405225-Drug Synergism,
pubmed-meshheading:9405225-Enzyme Inhibitors,
pubmed-meshheading:9405225-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:9405225-Glomerular Mesangium,
pubmed-meshheading:9405225-Humans,
pubmed-meshheading:9405225-Interleukin-1,
pubmed-meshheading:9405225-Isoenzymes,
pubmed-meshheading:9405225-Membrane Proteins,
pubmed-meshheading:9405225-Methotrexate,
pubmed-meshheading:9405225-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:9405225-Oxadiazoles,
pubmed-meshheading:9405225-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:9405225-Pteridines,
pubmed-meshheading:9405225-Pterins,
pubmed-meshheading:9405225-Quinoxalines,
pubmed-meshheading:9405225-RNA, Messenger,
pubmed-meshheading:9405225-Recombinant Proteins,
pubmed-meshheading:9405225-Transcription, Genetic,
pubmed-meshheading:9405225-Tumor Necrosis Factor-alpha
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pubmed:year |
1997
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pubmed:articleTitle |
Tetrahydrobiopterin modulates cyclooxygenase-2 expression in human mesangial cells.
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pubmed:affiliation |
Instituto "Reina Sofía" de Investigaciones Nefrológicas, C.S.I.C., Velázquez 144, Madrid, 28006, Spain. lperezsala@fresno.csic.es
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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