Role of adenosine transport in gestational diabetes-induced L-arginine transport and nitric oxide synthesis in human umbilical vein endothelium

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dc.contributor.authorVasquez, G
dc.contributor.authorSanhueza, F
dc.contributor.authorVasquez, R
dc.contributor.authorGonzalez, M
dc.contributor.authorSan Martin, R
dc.contributor.authorCasanello, P
dc.contributor.authorSobrevia, L
dc.date.accessioned2024-01-10T12:08:19Z
dc.date.available2024-01-10T12:08:19Z
dc.date.issued2004
dc.description.abstractGestational diabetes is associated with increased L-arginine transport and nitric oxide (NO) synthesis, and reduced adenosine transport in human umbilical vein endothelial cells (HUVEC). Adenosine increases endothelial L-arginine/NO pathway via A(2) purinoceptors in HUVEC from normal pregnancies. It is unknown whether the effect of gestational diabetes is associated with activation of these purinoceptors or altered expression of human cationic amino acid transporter 1 (hCAT-1) or human equilibrative nucleoside transporter I (hENT1), or endothelial NO synthase (eNOS) in HUVEC. Cells were isolated from normal or gestational diabetic pregnancies and cultured up to passage 2. Gestational diabetes increased hCAT-1 mRNA expression (2.4-fold) and activity, eNOS mRNA (2.3-fold), protein level (2.1-fold), and phosphorylation (3.8-fold), but reduced hENT1 mRNA expression (32%) and activity. Gestational diabetes increased extracellular adenosine (2.7 mum), and intracellular L-arginine (1.9 mm) and L-citrulline (0.7 mm) levels compared with normal cells (0.05 mum, 0.89 mm, 0.35 mm, respectively). Incubation of HUVEC from normal pregnancies with 1 mum nitrobenzylthioinosine (NBMPR) mimicked the effect of gestational diabetes, but NBMPR was ineffective in diabetic cells. Gestational diabetes and NBMPR effects involved eNOS, PKC and P42/44(mapk) activation, and were blocked by the A(2a) purinoceptor antagonist ZM-241385. Thus, gestational diabetes increases the L-arginine/NO pathway involving activation of mitogen-activated protein (MAP) kinases, protein kinase C (PKC) and NO cell signalling cascades following activation of A(2a) purinoceptors by extracellular adenosine. A functional relationship is proposed between adenosine transport and modulation Of L-arginine transport and NO synthesis in HUVEC, which could be determinant in regulating vascular reactivity in diabetes mellitus.
dc.fechaingreso.objetodigital2024-05-14
dc.format.extent12 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1113/jphysiol.2004.068288
dc.identifier.eissn1469-7793
dc.identifier.issn0022-3751
dc.identifier.pubmedidMEDLINE:15272035
dc.identifier.urihttps://doi.org/10.1113/jphysiol.2004.068288
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76381
dc.identifier.wosidWOS:000224464300010
dc.information.autorucMedicina;Casanello P;S/I;146772
dc.information.autorucMedicina;Sobrevia L;S/I;1002656
dc.issue.numero1
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final122
dc.pagina.inicio111
dc.publisherWILEY
dc.revistaJOURNAL OF PHYSIOLOGY-LONDON
dc.rightsacceso restringido
dc.subjectPROTEIN-KINASE-C
dc.subjectAMINO-ACID
dc.subjectD-GLUCOSE
dc.subjectSYSTEM Y(+)
dc.subjectACTIVATION
dc.subjectCELLS
dc.subjectEXPRESSION
dc.subjectSYNTHASE
dc.subjectINHIBITION
dc.subjectNUCLEOSIDE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRole of adenosine transport in gestational diabetes-induced L-arginine transport and nitric oxide synthesis in human umbilical vein endothelium
dc.typeartículo
dc.volumen560
sipa.codpersvinculados146772
sipa.codpersvinculados1002656
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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