Insulin-Stimulated L-Arginine Transport Requires SLC7A1 Gene Expression and Is Associated With Human Umbilical Vein Relaxation

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dc.contributor.authorGonzalez, Marcelo
dc.contributor.authorGallardo, Victoria
dc.contributor.authorRodriguez, Natalia
dc.contributor.authorSalomon, Carlos
dc.contributor.authorWestermeier, Francisco
dc.contributor.authorGuzman Gutierrez, Enrique
dc.contributor.authorAbarzua, Fernando
dc.contributor.authorLeiva, Andrea
dc.contributor.authorCasanello, Paola
dc.contributor.authorSobrevia, Luis
dc.date.accessioned2024-01-10T12:06:07Z
dc.date.available2024-01-10T12:06:07Z
dc.date.issued2011
dc.description.abstractInsulin causes endothelium-derived nitric oxide (NO)-dependent vascular relaxation, and increases L-arginine transport via cationic amino acid transporter 1 (hCAT-1) and endothelialNOsynthase (eNOS) expression and activity in human umbilical vein endothelium (HUVEC). We studied insulin effect on SLC7A1 gene (hCAT-1) expression and hCAT-transport activity role in insulin-modulated human fetal vascular reactivity. HUVEC were used for L-arginine transport and L-[H-3] citrulline formation (NOS activity) assays in absence or presence of N-ethylmaleimide (NEM) or L-lysine (L-arginine transport inhibitors). hCAT-1 protein abundance was estimated by Western blot, mRNA quantification by real time PCR, and SLC7A1 promoter activity by Luciferase activity (-1,606 and -650 bp promoter fragments from ATG). Specific protein 1 (Sp1), and total or phosphorylatedeNOSprotein was determined by Western blot. Sp1 activity (at four sites between -177 and -105 bp from ATG) was assayed by chromatin immunoprecipitation (ChIP) and vascular reactivity in umbilical vein rings. Insulin increased hCATs-L-arginine transport, maximal transport capacity (V-max/K-m), and hCAT-1 expression. NEM and L-lysine blocked L-arginine transport. In addition, it was trans-stimulated (similar to 7.8-fold) by L-lysine in absence of insulin, but unaltered (similar to 1.4-fold) in presence of insulin. Sp1 nuclear protein abundance and binding to DNA, and SLC7A1 promoter activity was increased by insulin. Insulin increasedNOsynthesis and caused endothelium-dependent vessel relaxation and reduced U46619-induced contraction, effects blocked by NEM and L-lysine, and dependent on extracellular L-arginine. We suggest that insulin induces human umbilical vein relaxation by increasing HUVEC L-arginine transport via hCATs (likely hCAT-1) most likely requiring Sp1-activated SLC7A1 expression. J. Cell. Physiol. 226: 2916-2924, 2011. (C) 2011 Wiley-Liss, Inc.
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT
dc.description.funderComision Nacional de Investigacion en Ciencia y Tecnologia (CONICYT)
dc.description.funderDireccion de Investigacion Universidad de Concepcion (DIUC)
dc.description.funderFaculty of Medicine, PUC-PhD (Chile)
dc.fechaingreso.objetodigital2024-04-27
dc.format.extent9 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1002/jcp.22635
dc.identifier.eissn1097-4652
dc.identifier.issn0021-9541
dc.identifier.pubmedidMEDLINE:21302286
dc.identifier.urihttps://doi.org/10.1002/jcp.22635
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76117
dc.identifier.wosidWOS:000295234800021
dc.information.autorucMedicina;Abarzua F ;S/I;84110
dc.information.autorucMedicina;Casanello P ;S/I;146772
dc.information.autorucCiencias Biológicas;Guzman E ;S/I;197588
dc.information.autorucMedicina;Leiva A ;S/I;3362
dc.information.autorucMedicina;Salomon C ;S/I;189546
dc.information.autorucMedicina;Sobrevia L ;S/I;1002656
dc.information.autorucCiencias Biológicas;Westermeier F ;S/I;181374
dc.issue.numero11
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final2924
dc.pagina.inicio2916
dc.publisherWILEY
dc.revistaJOURNAL OF CELLULAR PHYSIOLOGY
dc.rightsacceso restringido
dc.subjectFETAL ENDOTHELIAL DYSFUNCTION
dc.subjectSLC29A1 PROMOTER ACTIVITY
dc.subjectAMINO-ACID
dc.subjectNITRIC-OXIDE
dc.subjectTRANSCRIPTION FACTOR
dc.subjectDIABETES-MELLITUS
dc.subjectGLUCOSE
dc.subjectCELLS
dc.subjectCAT-1
dc.subjectPROTEIN-1
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInsulin-Stimulated L-Arginine Transport Requires SLC7A1 Gene Expression and Is Associated With Human Umbilical Vein Relaxation
dc.typeartículo
dc.volumen226
sipa.codpersvinculados84110
sipa.codpersvinculados146772
sipa.codpersvinculados197588
sipa.codpersvinculados3362
sipa.codpersvinculados189546
sipa.codpersvinculados1002656
sipa.codpersvinculados181374
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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