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Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells

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Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells

dc.contributor.author	Pérez-Cremades, Daniel
dc.contributor.author	Bueno-Betí, Carlos
dc.contributor.author	García-Giménez, José Luis
dc.contributor.author	Ibañez-Cabellos, José Santiago
dc.contributor.author	Hermenegildo, Carlos
dc.contributor.author	Pallardó, Federico V.
dc.contributor.author	Novella, Susana
dc.date.accessioned	2020-09-30T17:21:34Z
dc.date.available	2020-09-30T17:21:34Z
dc.date.issued	2017
dc.identifier.citation	Pérez-Cremades, Daniel Bueno-Betí, Carlos García-Giménez, José Luis Ibañez-Cabellos, José Santiago Hermenegildo, Carlos Pallardó, Federico V. Novella, Susana 2017 Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells Journal Of Cellular And Molecular Medicine 21 8 1584 1592
dc.identifier.uri	https://hdl.handle.net/10550/75709
dc.description.abstract	Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone-mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose-dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) mRNA and protein expression, decreased COX-1 mRNA levels and did not change thromboxane A2 synthase (TXAS) expression. Moreover, extracellular histones decreased both, eNOS expression and NO production in HUVEC. The impaired NO production was related to COX-2 activity and superoxide production since was reversed after celecoxib (10 μmol/l) and tempol (100 μmol/l) treatments, respectively. In conclusion, our findings suggest that extracellular histones stimulate the release of endothelial-dependent mediators through an up-regulation in COX-2-PGIS-PGI2 pathway which involves a COX-2-dependent superoxide production that decreases the activity of eNOS and the NO production. These effects may contribute to the endothelial cell dysfunction observed in histone-mediated pathologies.
dc.language.iso	eng
dc.relation.ispartof	Journal Of Cellular And Molecular Medicine, 2017, vol. 21, num. 8, p. 1584-1592
dc.subject	Òxid nítric
dc.subject	Proteïnes
dc.subject	Genètica humana
dc.title	Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells
dc.type	journal article	es_ES
dc.date.updated	2020-09-30T17:21:34Z
dc.identifier.doi	10.1111/jcmm.13088
dc.identifier.idgrec	115008
dc.rights.accessRights	open access	es_ES