Disease relevance of Ptgis

• Methods: We evaluated, by immunohistochemistry, Western blotting, and polymerase chain reaction, human emphysema tissue compared with normal tissue for expression of prostacyclin synthase (PGI(2)S) [1].
• Pulmonary prostacyclin synthase overexpression by adenovirus transfection and in transgenic mice [2].
• Nitric oxide synthase, prostacyclin synthase, and tissue inhibitors of metalloproteinases have been used to reduce neointima formation, and vein graft atheroma remains a challenge for the future [3].
• In a mouse hind limb ischemia model, cotransfection of the hepatocyte growth factor (HGF) gene with the prostacyclin synthase gene demonstrated a further increase in blood flow and capillary density compared with a single gene [4].
• Because peripheral neuropathy due to diabetes is common for significant morbidity, we examined the hypothesis that experimental diabetic neuropathy can be reversed by HGF and prostacyclin synthase genes [4].

High impact information on Ptgis

• Endothelial nitric oxide synthase-dependent tyrosine nitration of prostacyclin synthase in diabetes in vivo [5].
• The new entries of PGIS and PrP(c) in caveolar components place caveolae and CLDs at the centre of a network, where cells decide whether to proliferate or differentiate and whether to survive or to suicide by apoptosis [6].
• By generating prostacyclin, PGIS is involved in angiogenesis [6].
• We have shown that PGIS, previously described as an endoplasmic reticulum component, is bound to caveolin-1 (cav-1) and localized in caveolae in human endothelial cells [6].
• Evidence, that events occurring in caveolae participate in cell survival and angiogenesis, has been recently substantiated by the identification of two novel caveolar constituents: prostacyclin synthase (PGIS) and the cellular form of prion protein (PrP(c)) [6].

Biological context of Ptgis

• These observations suggested that the inverse gene expression of PGIS and TXS in macrophages contributes to immune responses by modulating the relative levels of prostacyclin and thromboxane A2 [7].
• To analyze the PGIS promoter activity, the 2.0 kb fragment was fused to the luciferase gene and transient transfection assays were conducted with cultured rat vascular smooth muscle cells (VSMC) [8].
• These results indicated that binding of one Sp1 to two Sp1 sites on the promoter region activated the basal transcription of the PGIS gene [8].
• Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene or optimization of intramuscular injection of naked plasmid DNA [9].

Anatomical context of Ptgis

• Northern blot analyses showed that the PGIS mRNA was expressed in a decreasing order in the resident, and casein- and BCG-elicited macrophages [7].
• METHODS AND RESULTS: Exposure of cultured human aortic endothelial cells to clinically relevant concentrations of CD40L (20 to 80 ng/mL) dose-dependently increased the production of superoxide (O2*-), decreased nitric oxide (NO) bioactivity, and increased PGIS nitration [10].
• COX-1, COX-2 and PGIS were expressed in 4-cell stage embryos and beyond; they were present in the inner cell mass and the trophectoderm of the blastocysts [11].

Associations of Ptgis with chemical compounds

• This effect was inhibited by 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid, an inhibitor of prostaglandin I2 synthase (Claesson, H.-E., Lindgren, J.A. and Hammarstr!om, S. (1977) FEBS Lett. 81, 415-418) [12].

Other interactions of Ptgis

• In situ hybridization analysis showed that the expression of mRNAs for PGIS and TXS was ascribable not only to the alteration of the expression levels of both mRNAs in the each macrophage but also to the changes in subpopulations of the cells expressing these mRNAs [7].
• In addition, mutation of two Sp1 recognition motifs residing at bases -297 to -289 and -197 to -192 markedly reduced the basal PGIS promoter activity and retarded the band in a gel mobility shift assay [8].

References