English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/170169
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Role of tetrahydrobiopterin availability in the regulation of nitric-oxide synthase expression in human mesangial cells

AuthorsSaura, Marta; Pérez-Sala, Dolores ; Cañada, F. Javier ; Lamas Peláez, Santiago
KeywordsVascular smooth-muscle
Sepiapterin reductase
Issue Date14-Jun-1996
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJ Biol Chem 271(24):14290-5 (1996)
AbstractHuman mesangial cells express an inducible form of nitric-oxide synthase (iNOS) after treatment with cytokines. Tetrahydrobiopterin (BH4), an essential cofactor for NOS, is required for cytokine-induced NO generation. We report here that BH4 is necessary not only for the activity but also for the expression of iNOS in human mesangial cells. Inhibition of de novo BH4 synthesis with 2,4-diamino-6-hydroxypyrimidine (DAHP) significantly attenuated iNOS activity as well as mRNA and protein expression in response to interleukin 1β plus tumor necrosis factor α (IL-1β/TNF-α). In contrast, sepiapterin, which provides BH4 through the pterin salvage pathway, strongly potentiated IL-1β/TNF-α-induced iNOS expression and abrogated the inhibitory effect of DAHP. Inhibition of the pterin salvage pathway with methotrexate abolished sepiapterin potentiation of iNOS induction but did not alter the effect of IL-1β/TNF-α. Determination of intracellular pteridines confirmed that sepiapterin markedly raised BH4 content, an effect that was blocked by methotrexate. These results suggest that BH4 availability plays an important role in the regulation of iNOS expression. The effect of BH4 appears to be mediated, at least in part, by an increase in mRNA stability, as indicated by the observation that DAHP shortened, whereas sepiapterin prolonged the half-life of IL-1β/TNF-α-induced iNOS mRNA. Taken together, our results suggest that the biosynthesis of BH4 contributes to cytokine induction of iNOS expression in human mesangial cells through the stabilization of iNOS mRNA.
Description7 p.-5 fig.
Publisher version (URL)http://dx.doi.org/ 10.1074/jbc.271.24.14290
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
J. Biol. Chem.-1996-Saura-14290-5.pdfArtículo principal287,22 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.