Prostaglandin endoperoxide synthase: why two isoforms?

@article{Williams1996ProstaglandinES,
  title={Prostaglandin endoperoxide synthase: why two isoforms?},
  author={C. S. Williams and Raymond N. DuBois},
  journal={The American journal of physiology},
  year={1996},
  volume={270 3 Pt 1},
  pages={
          G393-400
        }
}
Prostaglandin endoperoxide synthase-1 [prostaglandin G/H synthase-1 (PGHS-1)] and PGHS-2 are key enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. [...] Key Result Alterations in the expression levels of COX-2 result in distinct phenotypic changes in intestinal epithelial cells. Overexpression of COX-2 in intestinal epithelial cells results in increased adhesion to extracellular matrix proteins and inhibition of apoptosis.Expand
Flipping the cyclooxygenase (Ptgs) genes reveals isoform-specific compensatory functions1,2[S]
TLDR
Manipulation of COXs revealed isoform-specific compensatory functions and variable degrees of interchangeability for PG biosynthesis in cells/tissues. Expand
Visualization and quantitation of cyclooxygenase-1 and -2 activity by digital fluorescence microscopy.
  • R. Ornberg, A. Koki
  • Chemistry, Medicine
  • Advances in experimental medicine and biology
  • 1999
TLDR
Despite the similar catalytic activity and high amino acid sequence homology of the two isoforms, selective inhibitors have been synthesized for COX-2 and these are expected to provide a new therapy for arthritis and pain, inflammation, and cancer. Expand
Prostaglandins and Ovulation: From Indomethacin to PGHS-2 Knockout
The prostanoid family, which includes prostaglandins, prostacyclins, and thromboxanes, forms a group of potent mediators involved in numerous physiological processes, such as reproductive functionsExpand
Phorbol ester stimulates cyclooxygenase-2 expression and prostanoid production in cardiac myocytes.
TLDR
Findings indicate that PMA, acting through PKC and p38 kinase, enhances COX-2 expression, but chronic treatment with PMA partially inhibits IL-1beta stimulation of COx-2; and exogenous PGF(2alpha) is involved in neonatal ventricular myocyte growth but endogenous COX -2 products are not. Expand
Cancer and the Cyclo-Oxygenase Enzyme
TLDR
The role of the COX pathway in tumorigenesis, and the mechanisms, safety, and efficacy of COX nonselective and COX-2 selective inhibitors for cancer chemopreventive and chemotherapeutic applications are reviewed. Expand
Expression of Prostaglandin G/H Synthase Type 1, but not Type 2, in Human Ovarian Adenocarcinomas
TLDR
Results show for the first time that PGHS-1 is expressed in human ovarian adenocarcinomas. Expand
Trophic Effects of the Cyclooxygenase-2 Product Prostaglandin E2 in Cardiac Myocytes
TLDR
PGE2 production requires the induction of its specific synthase; in myocytes, the inducible enzymes COX-2 and PGES are perinuclear; and PGE2 and sulprostone induce cardiac myocyte growth but seem to activate a different subset of EP receptors. Expand
Suppression of cyclooxygenase-2 and inducible nitric oxide synthase expression by conjugated linoleic acid in murine macrophages.
TLDR
The results suggest that the anticarcinogenic effect of CLA in endotoxin-activated macrophages may be related to its ability to decrease both PGE(2) and NO synthesis by suppressing transcription of COX-2 and iNOS. Expand
Inhibition of prostaglandin synthesis up-regulates cyclooxygenase-2 induced by lipopolysaccharide and peroxisomal proliferators.
TLDR
The results indicate that COX-2 protein accumulates after enzyme inhibition, and because removal of the inhibitors restored the enzyme activity, suppression of treatment with reversible COx-2 inhibitors may cause a transient overproduction of prostaglandins. Expand
Regulation of prostaglandin biosynthesis in vivo by glutathione.
TLDR
The results indicate that elevated GSH levels inhibit PG production in this model and provide in vivo evidence for the role of GSH in the regulation of PG biosynthesis. Expand
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References

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Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse
TLDR
Mice lacking COX-2 have normal inflammatory responses to treatments with tetradecanoyl phorbol acetate or with arachidonic acid, however, they develop severe nephropathy and are susceptible to peritonitis. Expand
Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration
TLDR
COX-1-deficient mice provide a useful model to distinguish the physiological roles of COx-1 and COX-3, the target enzymes for the widely used nonsteroidal anti-inflammatory drugs. Expand
Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2
TLDR
It is demonstrated that overexpression of COX-2 leads to phenotypic changes in intestinal epithelial cells that could enhance their tumorigenic potential. Expand
Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II
TLDR
An animal model of COX-2 deficiency that was generated by gene targeting failed to alter inflammatory responses in several standard models, but striking mitigation of endotoxin-induced hepatocellular cytotoxicity was observed. Expand
Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines.
TLDR
The molecular cloning of human PHS type II from an endothelial cell cDNA library is reported and it is concluded that expression of PHS II may have important pathophysiological effects in the vasculature. Expand
Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic.
TLDR
Results suggest that inhibitors of COX-2 are potent antiinflammatory agents which do not produce the typical side effects associated with the nonselective,COX-1-directed antiinflammatory drugs. Expand
Prostaglandin endoperoxide synthase. The aspirin acetylation region.
TLDR
It is proposed that aspirin inhibits cyclooxygenase activity by placing a larger than normal side chain at position 530 thereby interfering with arachidonate binding and confirmed that residues 529-533 all are important for the peroxidase activity as well as the cyclo oxygenase activity of PGH synthase-1. Expand
Transient expression of prostaglandin endoperoxide synthase‐2 during mouse macrophage activation
TLDR
Data indicate that changes in PG synthesis following macrophage activation are due to regulation of PGHS‐2 expression, which is similar to that found in the case of PGE2 production. Expand
Endothelin stimulates prostaglandin endoperoxide synthase-2 mRNA expression and protein synthesis through a tyrosine kinase-signaling pathway in rat mesangial cells.
TLDR
It is concluded that in MC, ET-1 induces PGHS-2 through a protein tyrosine kinase-dependent pathway. Expand
Subcellular localization of prostaglandin endoperoxide synthase-2 in murine 3T3 cells.
TLDR
Colocalization of PGH synthases-1 and -2 implies that the source of arachidonate substrate, the site of P GH2 and prostanoid formation, and the mechanism of product transport from the inside to the outside of the cell are the same for these isozymes. Expand
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