Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/170169
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Role of tetrahydrobiopterin availability in the regulation of nitric-oxide synthase expression in human mesangial cells |
Autor: | Saura, Marta; Pérez-Sala, Dolores CSIC ORCID ; Cañada, F. Javier ; Lamas Peláez, Santiago CSIC ORCID | Palabras clave: | Vascular smooth-muscle L-arginine Sepiapterin reductase Biosynthesis Purification Requirements Cytokines Biopterin Cofactor Enzyme |
Fecha de publicación: | 14-jun-1996 | Editor: | American Society for Biochemistry and Molecular Biology | Citación: | J Biol Chem 271(24):14290-5 (1996) | Resumen: | Human 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. | Descripción: | 7 p.-5 fig. | Versión del editor: | http://dx.doi.org/ 10.1074/jbc.271.24.14290 | URI: | http://hdl.handle.net/10261/170169 | DOI: | 10.1074/jbc.271.24.14290 | ISSN: | 0021-9258 | E-ISSN: | 1083-351X |
Aparece en las colecciones: | (CIB) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
J. Biol. Chem.-1996-Saura-14290-5.pdf | Artículo principal | 287,22 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
37
checked on 13-abr-2024
WEB OF SCIENCETM
Citations
38
checked on 27-feb-2024
Page view(s)
266
checked on 22-abr-2024
Download(s)
211
checked on 22-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.