Disease relevance of Ptgis

• We conclude that PGIS plays a major role in modifying the pulmonary vascular response to chronic hypoxia [1].
• Repeated gene transfer of naked prostacyclin synthase plasmid into skeletal muscles attenuates monocrotaline-induced pulmonary hypertension and prolongs survival in rats [2].
• Thus, cPTIO may be beneficial in endotoxic shock because of NO scavenging and PGIS inactivation, which could be mediated by NO(2) [3].
• Increased splanchnic prostacyclin synthase and cyclooxygenase content and activity during ischemia is due to new protein synthesis [4].
• Post-suspension hypotension is attenuated in Sprague-Dawley rats by prostacyclin synthase inhibition [5].

High impact information on Ptgis

• Prostacyclin synthase (PGIS) is the final committed enzyme in the metabolic pathway leading to prostacyclin (PGI2) production [1].
• CONCLUSIONS: Inducible Ha-Ras(V12) increases the production of PGI(2) through the coordinate up-regulation of cPLA(2), COX-2, and prostacyclin synthase (PGIS) [6].
• Expression of prostaglandin H2-mediated mechanism of vascular contraction in hypertensive rats. Relation to lipoxygenase and prostacyclin synthase activities [7].
• Maximal velocity of thromboxane synthase and prostacyclin synthase, two more peripheral enzymes of the arachidonic acid cascade, were tissue-specifically enhanced, whereas the apparent affinities (Km) remained unchanged [8].
• Role for peroxynitrite in the inhibition of prostacyclin synthase in nitrate tolerance [9].

Chemical compound and disease context of Ptgis

• Acute hemorrhage stimulated a rapid induction of enzymes (cyclooxygenase, prostacyclin synthase) responsible for prostacyclin synthesis and release which were dependent on de novo protein synthesis [10].

Biological context of Ptgis

• Repeated PGIS gene transfer every week lowered RV systolic pressure and ameliorated RV and pulmonary artery remodeling in MCT-induced PH rats [2].
• Nevertheless, both drugs attenuated the increase in PGIS gene expression and plasma 6-keto-PGF(1alpha) levels (each P<0.05 vs. hypoxia) [11].
• We have reported that peroxynitrite (PON) selectively inactivated prostacyclin synthase (PGIS) by a mechanism of tyrosine nitration at the active site [Zou, Martin and Ullrich (1997) Biol. Chem. Hoppe-Seyler 378, 707-713] [12].
• Elevation of endogenous lipid peroxidation partially reversed this normal pregnancy trend in enzyme expression: prostaglandin endoperoxide synthase 1.85 fmol/ng deoxyribonucleic acid, prostacyclin synthase 9.38 units/ng deoxyribonucleic acid, thromboxane A2 synthase 4.36 units/ng deoxyribonucleic acid [13].
• Rat prostacyclin synthase. Cloning and regulation of gene expression in the lung [14].

Anatomical context of Ptgis

• In conclusion, repeated PGIS gene transfer into skeletal muscle not only attenuated the development of PH and cardiovascular remodeling but also improved the prognosis for MCT-induced PH rats [2].
• Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal formation in rat carotid arteries after balloon injury [15].
• Enzymatic analysis revealed that indapamide affected neither [14C]arachidonate liberation nor prostacyclin synthase of the smooth muscle cells [16].
• In contrast, prostacyclin synthase was present in granulosa cells of preantral (H and HE rats), SA, and PO follicles, was not induced by hCG, and was highest in thecal cells [17].
• Interleukin 1beta decreases prostacyclin synthase activity in rat mesangial cells via endogenous peroxynitrite formation [12].

Associations of Ptgis with chemical compounds

• A single injection of rat PGIS cDNA-encoding plasmid into thigh muscle 3 days after bupivacaine pretreatment transiently increased muscle PGIS protein expression and muscle and serum levels of a stable prostacyclin metabolite (6-keto-prostaglandin F1) [2].
• Conray did not significantly alter iNOS, COX-2, prostacyclin synthase, or PGE(2) synthase content [18].
• Indeed, the scavenging action of indapamide significantly attenuated the inhibitory activity of 15-hydroperoxy-arachidonate to prostacyclin synthase activity [16].
• Effect of an imidazolineoxyl nitric oxide on prostaglandin synthesis in experimental shock: possible role of nitrogen dioxide in prostacyclin synthase inactivation [3].
• PCS gene transfer and BPS 300 micrograms/kg/day significantly suppressed the BrdU index [19].

Other interactions of Ptgis

• Furthermore, the activity and expression of enzymes downstream of the COX step, such as prostacyclin synthase, were unaffected by CGP 28238 [20].
• Prostacyclin synthase gene transfer modulates cyclooxygenase-2-derived prostanoid synthesis and inhibits neointimal formation in rat balloon-injured arteries [21].
• Altered gene expression of prostacyclin synthase and prostacyclin receptor in the thoracic aorta of spontaneously hypertensive rats [22].
• Expression of prostacyclin synthase and argininosuccinate lyase, secondary enzymes of NO- and prostanoid-forming pathways, was not stimulated by db-cAMP [23].
• METHODS: Cerebral blood vessels from 17beta-estradiol-treated and nontreated ovariectomized rats were isolated and examined for prostacyclin synthesis by enzyme-linked immunosorbent assay or for protein levels of cyclooxygenase-1, prostacyclin-synthase, and cytosolic phospholipase A2 by immunoblot analysis [24].

Analytical, diagnostic and therapeutic context of Ptgis

• In addition, immunoprecipitation of nitrotyrosine-containing proteins from PON- and SIN-1-treated RMC yielded distinct nitrated PGIS bands but also from IL-1beta-pretreated cells alone, compared with a lack of nitrated PGIS in control cells [12].
• The renal cortex and medulla were separated and analyzed for inducible nitric oxide synthase (iNOS), cyclooxygenase-2, prostacyclin synthase, and PGE2 synthase content by Western blot [25].
• The survival ratio was significantly higher in the prostacyclin synthase group than the control group (P =.0375) [26].
• Prostaglandin I2 synthase in the lymphatic endothelium of rat liver as revealed by preembedding immunoelectron microscopy [27].

References