• Metabolism of arachidonic acid through cyclooxygenase (COX) enzymes is known to be actively involved in the neuroinflammatory events leading to neuronal death after ischemia. (southampton.ac.uk)
  • By 1964, after recognition of this basic structure, Bergstrom and colleagues successfully synthesized series 2 prostaglandins from arachidonic acid using sheep seminal fluid. (medscape.com)
  • Their distinct biosynthetic activity includes an endoperoxidase synthase reaction that oxygenates and cyclizes polyunsaturated fatty acid precursors (eg, arachidonic acid) to form prostaglandin G 2 (PGG2), and a peroxidase reaction that converts PGG2 to prostaglandin H 2 (PGH2), as shown below. (medscape.com)
  • Cyclooxygenase conversion of arachidonic acid into prostaglandin H2 (PGH2). (medscape.com)
  • Cyclooxygenase inhibition in ischemic brain injury. (southampton.ac.uk)
  • We will discuss issues related to the biochemistry and selective pharmacological inhibition of COX enzymes, and further refer to their expression in the brain under normal conditions and following excitotoxicity and ischemic cerebral injury. (southampton.ac.uk)
  • Cyclooxygenase inhibition as a strategy to ameliorate brain injury. (southampton.ac.uk)
  • [ 1 ] Thus, tracing research of the COX pathway is essential to an understanding of COX deficiency, and examining the variable effects of COX inhibition are advantageous. (medscape.com)
  • Unlike traditional nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors, AK106-001616 reduced prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) production by stimulated cells. (aspetjournals.org)
  • We will review present knowledge of the relative contribution of each COX isoform to the brain ischemic pathology, based on data from investigations utilizing selective COX-1/COX-2 inhibitors and genetic knockout mouse models. (southampton.ac.uk)
  • Finally, we will provide a critical evaluation of the therapeutic potential of COX inhibitors in cerebral ischemia and discuss new targets downstream of COX with potential neuroprotective ability. (southampton.ac.uk)
  • 3-[3-Amino-4-(indan-2-yloxy)-5-(1-methyl-1 H -indazol-5-yl)-phenyl]-propionic acid (AK106-001616) is a novel, potent, and selective inhibitor of the cytosolic phospholipase A 2 (cPLA 2 ) enzyme. (aspetjournals.org)
  • DuP 697 is a potent and selective inhibitor of cyclooxygenase-2 (IC 50 values are 10 and 800 nM for COX-2 and COX-1 respectively). (tocris.com)
  • Collectively, these landmark discoveries provided initial insight into the COX pathway of arachidonate metabolism. (medscape.com)
  • Regardless of the etiology, a deficiency of cyclooxygenase (COX), a key regulatory enzyme in the synthetic pathway of eicosanoid production, results in beneficial and detrimental physiologic conditions relative to imbalances of the eicosanoids. (medscape.com)
  • Therefore, COX - also known as prostaglandin-endoperoxide synthase (PTGS), fatty acid COX, prostaglandin H (PGH) synthase, and EC 1.14.99.1 - is implicated in the production of fever, inflammation, and pain. (medscape.com)
  • However, the physiologic significance of prostaglandin production did not unfold until 1971, when Vane, Smith, and Willis discovered that aspirin and indomethacin inhibited prostaglandin biosynthesis. (medscape.com)
  • In turn, PGH2 is converted to biologically active products (ie, prostaglandin E 2 [PGE2]) by individual synthase and reductase reactions. (medscape.com)
  • The mechanisms of neurotoxicity associated with increased COX activity after ischemia will also be examined. (southampton.ac.uk)
  • He localized the biologic activity to a fraction of lipid soluble acids that he termed "prostaglandin," hypothesizing that these substances originate in the prostate gland. (medscape.com)
  • Prostanoids are derived from arachidonic acid by the sequential actions of phospholipase A(2), cyclooxygenase (COX), and specific prostaglandin (PG) synthases. (nih.gov)
  • A major interest in the Marnett laboratory is the structure and function of cyclooxygenase-2 (COX-2). (vanderbilt.edu)
  • Functional analysis of COX-2 by structure-guided mutagenesis has uncovered new strategies for synthesizing COX-2 inhibitors and has suggested new biological roles for the enzyme. (vanderbilt.edu)
  • This enzyme catalyzes the committed step in the production of prostaglandins and is the molecular target for non-steroidal antiinflammatory drugs. (vanderbilt.edu)
  • Current work focuses on the generation of novel antiinflammatory drugs with additional pharmacological functions and on investigations of the chemistry and biology of COX-2-dependent oxygenation of the endocannabinoid, 2-arachidonylglycerol, to glyceryl prostaglandins. (vanderbilt.edu)