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http://purl.uniprot.org/citations/14551150http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14551150http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Synthesis of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases, is strongly induced on immunostimulation in vascular endothelial cells (VECs). Expression of GTP cyclohydrolase I (GTPCH), the first enzyme in BH4 biosynthesis, is regulated by cytokines and considered rate-limiting. Herein we investigated the molecular mechanism and relevance of cytokine-dependent regulation of 6-pyruvoyltetrahydropterin synthase (PTPS), the second enzyme in BH4 synthesis, in human coronary artery endothelial cells (HCAECs).

Methods and results

Real-time polymerase chain reaction revealed a 4-fold induction of PTPS and a 300-fold induction of GTPCH expression by interleukin (IL)-1beta/tumor necrosis factor-alpha/interferon-gamma, mainly through de novo transcription. On immunostimulation, PTPS became rate-limiting. Importantly, IL-1beta induced PTPS rather than GTPCH. As a result, IL-1beta contributed significantly to the amount of BH4 produced (+40%) but concomitantly reduced the accumulation of the GTPCH intermediate, 7,8-dihydroneopterin triphosphate (-50%).

Conclusions

Our data show that PTPS induction is necessary for optimized BH4 synthesis in cytokine-stimulated HCAECs and point to IL-1beta as a leading cytokine in this process."xsd:string
http://purl.uniprot.org/citations/14551150http://purl.org/dc/terms/identifier"doi:10.1161/01.atv.0000099785.65848.f1"xsd:string
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/author"Schaffner A."xsd:string
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/author"Schoedon G."xsd:string
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/author"Blau N."xsd:string
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/author"Walter R.B."xsd:string
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/author"Franscini N."xsd:string
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/pages"e50-3"xsd:string
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/title"Critical role of interleukin-1beta for transcriptional regulation of endothelial 6-pyruvoyltetrahydropterin synthase."xsd:string
http://purl.uniprot.org/citations/14551150http://purl.uniprot.org/core/volume"23"xsd:string
http://purl.uniprot.org/citations/14551150http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/14551150
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