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http://purl.uniprot.org/citations/20947827http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20947827http://www.w3.org/2000/01/rdf-schema#comment"

Objective

The thromboxane receptor (TPr) and multiple TPr ligands, including thromboxane A(2) (TxA(2)) and prostaglandin H(2), are elevated during vascular and atherothrombotic diseases. How TPr stimulation causes vascular injury remains poorly defined. This study was conducted to investigate the mechanism by which TPr stimulation leads to vascular injury.

Methods and results

Exposure of bovine aortic endothelial cells to either [1S-(1α,2β(5Z),3α(1E,3R),4α]-7-[3-(3-hydroxy-4-(d'-iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1] heptan-2-yl]-5'-heptenoic acid (IBOP) or U46619, 2 structurally related TxA(2) mimetics, for 24 hours markedly increased the release of superoxide anions (O(2)(·-)) and peroxynitrite (ONOO(-)) but reduced cyclic GMP, an index of nitric oxide bioactivity. IBOP also significantly suppressed activity of endothelial nitric oxide synthase (eNOS), increased enzyme-inactive eNOS monomers, and reduced levels of tetrahydrobiopterin, an essential eNOS cofactor. IBOP- and U46619-induced increases in O(2)(·-) were accompanied by the membrane translocation of the p67(phox) subunit of NAD(P)H oxidase. Pharmacological or genetic inhibition of either NAD(P)H oxidase or TPr abolished IBOP-induced O(2)(·-) formation. Furthermore, TPr activation significantly increased protein kinase C-ζ (PKC-ζ) in membrane fractions and PKC-ζ phosphorylation at Thr410. Consistently, PKC-ζ inhibition abolished TPr activation-induced membrane translocation of p67(phox) and O(2)(·-) production. Finally, exposure of isolated mouse aortae to IBOP markedly increased O(2)(·-) in wild-type but not in those from gp91(phox) knockout mice.

Conclusions

We conclude that TPr activation via PKC-ζ-mediated NAD(P)H oxidase activation increases both O(2)(·-) and ONOO(-), resulting in eNOS uncoupling in endothelial cells."xsd:string
http://purl.uniprot.org/citations/20947827http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.110.207712"xsd:string
http://purl.uniprot.org/citations/20947827http://purl.uniprot.org/core/author"Xu J."xsd:string
http://purl.uniprot.org/citations/20947827http://purl.uniprot.org/core/author"Zhang M."xsd:string
http://purl.uniprot.org/citations/20947827http://purl.uniprot.org/core/author"Song P."xsd:string
http://purl.uniprot.org/citations/20947827http://purl.uniprot.org/core/author"Zou M.H."xsd:string
http://purl.uniprot.org/citations/20947827http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/20947827http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/20947827http://purl.uniprot.org/core/pages"125-132"xsd:string
http://purl.uniprot.org/citations/20947827http://purl.uniprot.org/core/title"Activation of NAD(P)H oxidases by thromboxane A2 receptor uncouples endothelial nitric oxide synthase."xsd:string
http://purl.uniprot.org/citations/20947827http://purl.uniprot.org/core/volume"31"xsd:string
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