Disease relevance of PTGIS

• Hypoxia-reoxygenation triggers coronary vasospasm in isolated bovine coronary arteries via tyrosine nitration of prostacyclin synthase [1].

High impact information on PTGIS

• Concentrations of prostaglandin endoperoxide synthase and prostaglandin I2 synthase in the endothelium and smooth muscle of bovine aorta [2].
• Specific nitration at tyrosine 430 revealed by high resolution mass spectrometry as basis for redox regulation of bovine prostacyclin synthase [3].
• Similarly, bovine prostacyclin synthase catalyzed the isomerization of the intermediate endoperoxides, PGH(2)-G and PGH(2)-EA, to the corresponding prostacyclin derivatives [4].
• Selective nitration of prostacyclin synthase and defective vasorelaxation in atherosclerotic bovine coronary arteries [5].
• These data suggest that reduced PCS activity in atherosclerotic arteries prevents the rapid use of PGH2, which accumulates and acts as an agonist on the vasoconstrictive thromboxane receptor [5].

Biological context of PTGIS

• In the present study, we determined the amino acid sequence of bovine prostacyclin synthase by combined protein chemical and molecular cloning techniques [6].
• COS-7 cells transfected with an expression plasmid harboring this cDNA clone expressed prostacyclin synthase activity [6].
• Prostacyclin synthase catalyzes the conversion of prostaglandin H2 to prostacyclin, which is a powerful vasodilator and the most potent natural occurring inhibitor of platelet aggregation [6].
• The cDNA encoding prostacyclin synthase (PGIS) was isolated from a bovine arota cDNA library [7].
• Cellular distribution of prostacyclin synthase and specific prostacyclin binding sites in bovine corpora lutea of pregnancy [8].

Anatomical context of PTGIS

• RNA blot analysis indicated that the mRNA for prostacyclin synthase from bovine endothelial cells showed a size of approximately 2.7 kilobases and that the mRNA level increased about 3-fold by treatment of tumor necrosis factor-alpha [6].
• Immunoprecipitation with antibodies raised against nitrotyrosine yielded PCS as the main nitrated protein in blood vessels [5].
• As shown by enzyme activity precipitation and Western blot analysis, in solubilized bovine and porcine aortae microsomes the monoclonal antibodies reacted only with prostacyclin synthase [9].
• The monoclonal antibody RS1 cross-reacts with partially purified prostacyclin synthase from human umbilical veins in an ELISA-based assay [9].

Associations of PTGIS with chemical compounds

• PGIS shares only 16% sequence identity with human thromboxane synthase and has a different hydropathy pattern near the amino terminus, suggesting a different membrane anchoring topology [7].
• The effect of various oxidants on bovine aortic prostacyclin synthase was tested with 14C-labelled prostaglandin endoperoxide as substrate [10].
• Peroxynitrite formed by simultaneous generation of nitric oxide and superoxide selectively inhibits bovine aortic prostacyclin synthase [10].
• Studies on the interaction of minoxidil with prostacyclin synthase in vitro [11].
• These findings coupled with our earlier demonstration of a requisite addition of exogenous arachidonate in order to observe strain-induced PGI2 release, implicates a mechanism that more likely involves strain-induced stimulation of PGIS activity [12].

Analytical, diagnostic and therapeutic context of PTGIS

• Isolation and molecular cloning of prostacyclin synthase from bovine endothelial cells [6].
• Results based on (1) elution profile of the Mono Q column, (2) two-dimensional gel electrophoresis and (3) N-terminal amino acid sequence suggested that PGIS is heterogenous [13].
• After immobilization to Protein A-sepharose, the PGIS-antibody complex displayed PGIS activity [13].
• Prostacyclin synthase (PGIS) from bovine aorta was purified using conventional purification procedures including detergent solubilization, Sephacryl S-300 gel filtration and Mono Q high performance liquid chromatography [13].
• By combination of the monoclonal antibody RS2 with a polyclonal antibody we established an enzyme-linked immunosorbent assay (ELISA) for quantitation of bovine prostacyclin synthase [9].

References