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dc.contributor.authorSaura, Martaes_ES
dc.contributor.authorPérez-Sala, Doloreses_ES
dc.contributor.authorCañada, F. Javieres_ES
dc.contributor.authorLamas Peláez, Santiagoes_ES
dc.date.accessioned2018-09-25T12:01:41Z-
dc.date.available2018-09-25T12:01:41Z-
dc.date.issued1996-06-14-
dc.identifier.citationJ Biol Chem 271(24):14290-5 (1996)es_ES
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10261/170169-
dc.description7 p.-5 fig.es_ES
dc.description.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.es_ES
dc.description.sponsorshipThis work was supported by Grants PB93-0044 (to S. L.) and PB93-0127 (to F. J. C.) from the Dirección General de Investigación Científica y Técnica (DGICYT).es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rightsopenAccesses_ES
dc.subjectVascular smooth-musclees_ES
dc.subjectL-argininees_ES
dc.subjectSepiapterin reductasees_ES
dc.subjectBiosynthesises_ES
dc.subjectPurificationes_ES
dc.subjectRequirementes_ES
dc.subjectCytokineses_ES
dc.subjectBiopterines_ES
dc.subjectCofactores_ES
dc.subjectEnzymees_ES
dc.titleRole of tetrahydrobiopterin availability in the regulation of nitric-oxide synthase expression in human mesangial cellses_ES
dc.typeartículoes_ES
dc.identifier.doi10.1074/jbc.271.24.14290-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/ 10.1074/jbc.271.24.14290es_ES
dc.identifier.e-issn1083-351X-
dc.contributor.funderDirección General de Investigación Científica y Técnica, DGICT (España)es_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100008737es_ES
dc.contributor.orcidPérez-Sala, Dolores [0000-0003-0600-665X]es_ES
dc.contributor.orcidCañada, F. Javier [0000-0003-4462-1469]es_ES
dc.contributor.orcidLamas Peláez, Santiago [0000-0001-5166-4155]es_ES
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