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http://purl.uniprot.org/citations/25278292http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25278292http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Hemoglobin α (Hb α) and endothelial nitric oxide synthase (eNOS) form a macromolecular complex at myoendothelial junctions; the functional role of this interaction remains undefined. To test if coupling of eNOS and Hb α regulates nitric oxide signaling, vascular reactivity, and blood pressure using a mimetic peptide of Hb α to disrupt this interaction.

Approach and results

In silico modeling of Hb α and eNOS identified a conserved sequence of interaction. By mutating portions of Hb α, we identified a specific sequence that binds eNOS. A mimetic peptide of the Hb α sequence (Hb α X) was generated to disrupt this complex. Using in vitro binding assays with purified Hb α and eNOS and ex vivo proximity ligation assays on resistance arteries, we have demonstrated that Hb α X significantly decreased interaction between eNOS and Hb α. Fluorescein isothiocyanate labeling of Hb α X revealed localization to holes in the internal elastic lamina (ie, myoendothelial junctions). To test the functional effects of Hb α X, we measured cyclic guanosine monophosphate and vascular reactivity. Our results reveal augmented cyclic guanosine monophosphate production and altered vasoconstriction with Hb α X. To test the in vivo effects of these peptides on blood pressure, normotensive and hypertensive mice were injected with Hb α X, which caused a significant decrease in blood pressure; injection of Hb α X into eNOS(-/-) mice had no effect.

Conclusions

These results identify a novel sequence on Hb α that is important for Hb α/eNOS complex formation and is critical for nitric oxide signaling at myoendothelial junctions."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.114.303974"xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Columbus L."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Johnson T."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Billaud M."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Nguyen A.T."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Miller M.P."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Le T.H."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Mutchler S.M."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Straub A.C."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Somlyo A.V."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Best A.K."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Isakson B.E."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Butcher J.T."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Palmer L.A."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/author"Artamonov M.V."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/pages"2594-2600"xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/title"Hemoglobin alpha/eNOS coupling at myoendothelial junctions is required for nitric oxide scavenging during vasoconstriction."xsd:string
http://purl.uniprot.org/citations/25278292http://purl.uniprot.org/core/volume"34"xsd:string
http://purl.uniprot.org/citations/25278292http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25278292
http://purl.uniprot.org/citations/25278292http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25278292
http://purl.uniprot.org/uniprot/#_E9Q9X4-mappedCitation-25278292http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25278292
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