Hypoxia-reduced nitric oxide synthase activity is partially explained by higher arginase-2 activity and cellular redistribution in human umbilical vein endothelium

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dc.contributor.authorPrieto, C. P.
dc.contributor.authorKrause, B. J.
dc.contributor.authorQuezada, C.
dc.contributor.authorSan Martin, R.
dc.contributor.authorSobrevia, L.
dc.contributor.authorCasanello, P.
dc.date.accessioned2024-01-10T13:13:35Z
dc.date.available2024-01-10T13:13:35Z
dc.date.issued2011
dc.description.abstractHypoxia relates with altered placental vasodilation, and in isolated endothelial cells, it reduces activity of the endothelial nitric oxide synthase (eNOS) and L-arginine transport. It has been reported that arginase-2 expression, an alternative pathway for L-arginine metabolism, is increased in adult endothelial cells exposed to hypoxia as well as in pre-eclamptic placentae. We studied in human umbilical vein endothelial cells (HUVEC) whether hypoxia-reduced NO synthesis results from increased arginase-mediated L-arginine metabolism and changes in subcellular localization of eNOS and arginase-2. In HUVEC exposed (24 h) to 5% (normoxia) or 2% (hypoxia) oxygen, L-arginine transport kinetics, arginase activity (urea assay), and NO synthase (NOS) activity (L-citrulline assay) were determined. Arginase-1, arginase-2 and eNOS expression were determined by RT-PCR and Western blot. Subcellular localization of arginase-2 and eNOS were studied using confocal microscopy and indirect immunofluorescence. Experiments were done in absence or presence of S-(2-boronoethyl)-L-cysteine-HCl (BEC, arginase inhibitor) or N-G-nitro-L-arginine methyl ester (L-NAME). Hypoxia-induced reduction in eNOS activity was associated with a reduction in eNOS phosphorylation at Serine-1177 and increased phosphorylation at Threonine-495. This was paralleled with an induction in arginase-2 expression and activity, and decreased L-arginine transport. In hypoxia the arginase inhibition, restored NO synthesis and L-arginine transport, without changes in the eNOS post-translational modification status. Hypoxia increased arginase-2/eNOS colocalization, and eNOS redistribution to the cell periphery. Altogether these data reinforce the thought that eNOS cell location, post-translational modification and substrate availability are important mechanisms regulating eNOS activity. If these mechanisms occur in pregnancy diseases where feto-placental oxygen levels are reduced remains to be clarified. (C) 2011 Elsevier Ltd. All rights reserved.
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT)
dc.description.funderPrograma de Investigacion Interdisciplinario (PIA), Comision Nacional de Investigacion en Ciencia y Tecnologia (CONICYT)
dc.description.funderCONICYT
dc.description.funderApoyo a la Realizacion de la Tesis Doctoral, CONICYT
dc.fechaingreso.objetodigital05-04-2024
dc.format.extent9 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.placenta.2011.09.003
dc.identifier.eissn1532-3102
dc.identifier.issn0143-4004
dc.identifier.pubmedidMEDLINE:21962305
dc.identifier.urihttps://doi.org/10.1016/j.placenta.2011.09.003
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78318
dc.identifier.wosidWOS:000298459400003
dc.information.autorucMedicina;Casanello P ;S/I;146772
dc.information.autorucMedicina;Krause B;S/I;1005678
dc.information.autorucMedicina;Sobrevia L;S/I;1002656
dc.issue.numero12
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final940
dc.pagina.inicio932
dc.publisherW B SAUNDERS CO LTD
dc.revistaPLACENTA
dc.rightsacceso restringido
dc.subjectPlacenta
dc.subjectArginase
dc.subjectEndothelium
dc.subjectHuman
dc.subjectNitric oxide
dc.subjectHypoxia
dc.subjectUP-REGULATION
dc.subjectDYSFUNCTION
dc.subjectACTIVATION
dc.subjectEXPRESSION
dc.subjectTRANSPORTER-1
dc.subjectHYPERTENSION
dc.subjectCELLS
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHypoxia-reduced nitric oxide synthase activity is partially explained by higher arginase-2 activity and cellular redistribution in human umbilical vein endothelium
dc.typeartículo
dc.volumen32
sipa.codpersvinculados146772
sipa.codpersvinculados1005678
sipa.codpersvinculados1002656
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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