High D-Glucose reduces SLC29A1 promoter activity and adenosine transport involving specific protein 1 in human umbilical vein endothelium

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dc.contributor.authorPuebla, Carlos
dc.contributor.authorFarias, Marcelo
dc.contributor.authorGonzalez, Marcelo
dc.contributor.authorVecchiola, Andrea
dc.contributor.authorAguayo, Claudio
dc.contributor.authorKrause, Bernardo
dc.contributor.authorPastor Anglada, Marcal
dc.contributor.authorCasanello, Paola
dc.contributor.authorSobrevia, Luis
dc.date.accessioned2024-01-10T12:05:49Z
dc.date.available2024-01-10T12:05:49Z
dc.date.issued2008
dc.description.abstractHigh D-glucose reduces human equilibrative nucleoside transporter 1 (hENT1)-mediated adenosine uptake involving endothelial nitric oxide synthase (eNOS), mitogen-activated protein (MAP) kinase kinases 1 and 2/MAP kinases p42/44 (MEK/ERKs), and protein kinase C (PKC) activation in human umbilical vein endothelium (HUVEC). Since NO represses SLC29A1 gene (hENT1) promoter activity we studied whether D-glucose-reduced hENT1-adenosine transport results from lower SLC29A1 expression in HUVEC primary cultures. HUVEC incubation (24 h) with high D-glucose (25 mM) reduced hENT1-adenosine transport and pGL3-hENT1(-1114) construct SLC29A1 reporter activity compared with normal D-glucose (5 mM). High D-glucose also reduced pGL3-hENT1(-1114) reporter activity compared with cells transfected with pGL3-hENT1(-795) Construct. N-G-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor), PD-98059 (MEK1/2 inhibitor), and/or calphostin C (PKC inhibitor) blocked D-glucose effects. Insulin(1 nM) and phorbol 12-myristate 13-acetate (PMA, 100 nM, PKC activator), but not 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD, 100 nM, PMA less active analogue) reduced hENT1-adenosine transport. L-NAME and PD-98059 blocked insulin effects. L-NAME, PD-98059, and calphostin C increased hENT1 expression without altering protein or mRNA stability. High D-glucose increased Sp1 transcription factor protein abundance and binding to SLC29A1 promoter, phenomena blocked by L-NAME, PD-98059, and calphostin C. Sp1 overexpression reduced SLC29A1 promoter activity in normal D-glucose, an effect reversed by L-NAME and further reduced by S-nitroso-N-acetyl-L,D-penicillamine (SNAP, NO donor) in high D-glucose. Thus, reduced hENT1 -mediated adenosine transport in high D-glucose may result from increased Sp1 binding to SLC29A1 promoter down-regulating hENT1 expression. This phenomenon depends on eNOS, MEK/ERKs, and PKC activity, suggesting potential roles for these molecules in hyperglycemia-associated endothelial dysfunction.
dc.fechaingreso.objetodigital2024-04-27
dc.format.extent12 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1002/jcp.21347
dc.identifier.eissn1097-4652
dc.identifier.issn0021-9541
dc.identifier.pubmedidMEDLINE:18064606
dc.identifier.urihttps://doi.org/10.1002/jcp.21347
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76072
dc.identifier.wosidWOS:000255699500010
dc.information.autorucQuímica;Aguayo C;S/I;129616
dc.information.autorucMedicina;Casanello P;S/I;146772
dc.information.autorucMedicina;Farías M;S/I;12286
dc.information.autorucCiencias Biológicas;Krause B;S/I;1005678
dc.information.autorucCiencias Biológicas;Puebla C;S/I;124965
dc.information.autorucMedicina;Sobrevia L;S/I;1002656
dc.information.autorucMedicina;Vecchiola A;S/I;123319
dc.issue.numero3
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final656
dc.pagina.inicio645
dc.publisherWILEY
dc.revistaJOURNAL OF CELLULAR PHYSIOLOGY
dc.rightsacceso restringido
dc.subjectEQUILIBRATIVE NUCLEOSIDE TRANSPORTER-2
dc.subjectNITRIC-OXIDE
dc.subjectKINASE-C
dc.subjectTRANSCRIPTION FACTOR
dc.subjectGENE-EXPRESSION
dc.subjectINSULIN
dc.subjectSP1
dc.subjectINVOLVEMENT
dc.subjectINHIBITION
dc.subjectALPHA
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHigh D-Glucose reduces SLC29A1 promoter activity and adenosine transport involving specific protein 1 in human umbilical vein endothelium
dc.typeartículo
dc.volumen215
sipa.codpersvinculados129616
sipa.codpersvinculados146772
sipa.codpersvinculados12286
sipa.codpersvinculados1005678
sipa.codpersvinculados124965
sipa.codpersvinculados1002656
sipa.codpersvinculados123319
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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