Nitric oxide reduces <i>SLC29A1</i> promoter activity and adenosine transport involving transcription factor complex hCHOP-C/EBPα in human umbilical vein endothelial cells from gestational diabetes

Simple item page
dc.contributor.authorFarias, Marcelo
dc.contributor.authorPuebla, Carlos
dc.contributor.authorWestermeier, Francisco
dc.contributor.authorJo, Miguel J.
dc.contributor.authorPastor-Anglada, Marcal
dc.contributor.authorCasanello, Paola
dc.contributor.authorSobrevia, Luis
dc.date.accessioned2025-01-21T00:06:15Z
dc.date.available2025-01-21T00:06:15Z
dc.date.issued2010
dc.description.abstractReduced expression of human equilibrative nucleoside transporter 1 (hENT1) results from nitric oxide (NO)-dependent reduced SLC29A1 transcriptional activity in human umbilical vein endothelial cells (HUVECs) from gestational diabetes. As expression of the transcription factor C/EBP homologous protein 10 (hCHOP, which forms heterodimers with C/EBP alpha transcription factor) is activated by NO and induced in diabetes mellitus, we hypothesize that hCHOP plays a role in the gestational diabetes-reduced hENT1 expression in HUVECs.
dc.description.abstractHUVEC primary cultures from 42 normal and 42 gestational diabetic pregnancies were used for adenosine uptake assays. Real-time PCR (mRNA quantification), western blotting (protein abundance), and luciferase activity (SLC29A1 promoter activity) were used. hCHOP-C/EBP alpha activity was assayed by chromatin immunoprecipitation. Overlap extension mutagenesis was used to generate a mutated hCHOP-C/EBP alpha consensus site at the SLC29A1 promoter, and endothelial NO synthase (eNOS) siRNA recombinant adenovirus was used to knock down eNOS. hCHOP nuclear protein abundance and binding to DNA were higher in gestational diabetes, paralleled by reduced SLC29A1 promoter activity, hENT1 expression, and transport activity. These changes were blocked by hCHOP consensus sequence mutation (-1845G > T and -1844C > A), eNOS-siRNA-induced knockdown, and N-G-nitro-l-arginine methyl ester (NOS inhibitor), and were mimicked by S-nitroso-N-acetyl-l, d-penicillamine (NO donor) in cells from normal pregnancies. hCHOP and C/EBP alpha overexpression mimicked gestational diabetes effects in cells from normal pregnancies, but did not alter SLC29A1 promoter activity or hENT1-adenosine transport in cells from gestational diabetes.
dc.description.abstractThe hCHOP-C/EBP alpha complex down-regulates SLC29A1 expression in an NO-dependent manner in HUVECs from gestational diabetes.
dc.fuente.origenWOS
dc.identifier.doi10.1093/cvr/cvp410
dc.identifier.eissn1755-3245
dc.identifier.issn0008-6363
dc.identifier.urihttps://doi.org/10.1093/cvr/cvp410
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95581
dc.identifier.wosidWOS:000275566400009
dc.issue.numero1
dc.language.isoen
dc.pagina.final54
dc.pagina.inicio45
dc.revistaCardiovascular research
dc.rightsacceso restringido
dc.subjectAdenosine
dc.subjectDiabetes
dc.subjectEndothelium
dc.subjectTranscription factor
dc.subjectCHOP
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNitric oxide reduces <i>SLC29A1</i> promoter activity and adenosine transport involving transcription factor complex hCHOP-C/EBPα in human umbilical vein endothelial cells from gestational diabetes
dc.typeartículo
dc.volumen86
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas