Publications by authors named "C A Rouzer"

Cyclooxygenase-2 converts arachidonic acid to prostaglandins (PGs) and the endocannabinoid, 2-arachidonoylglycerol (2-AG), to PG glyceryl esters (PG-Gs). The physiological function of PG biosynthesis has been extensively studied, but the importance of the more recently discovered PG-G synthetic pathway remains incompletely defined. This disparity is due in part to a lack of knowledge of the physiological conditions under which PG-G biosynthesis occurs.

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Article Synopsis
  • Necrostatin-1 inhibits both ferroptosis and necroptosis via different mechanisms, including blocking RIP1 kinase and suppressing prostaglandin production in macrophages.
  • Different compounds, including necrostatin-1i and various ferroptosis inhibitors, effectively reduce prostaglandin biosynthesis, albeit through distinct pathways and potencies, suggesting varied mechanisms of action.
  • The study reveals that while ferroptosis inhibitors lower cyclooxygenase-2 activity by reducing hydroperoxide levels, necrostatin-1's prostaglandin synthesis inhibition relies on a specific chemical structure rather than redox activity, pointing to diverse therapeutic potentials of these compounds.
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The lipid peroxidation product malondialdehyde and the DNA peroxidation product base-propenal react with dG to generate the exocyclic adduct, MdG. This mutagenic lesion has been found in human genomic and mitochondrial DNA. MdG in genomic DNA is enzymatically oxidized to 6-oxo-MdG, a lesion of currently unknown mutagenic potential.

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The Cyclooxygenase enzymes (COX-1 and COX-2) incorporate 2 molecules of O into arachidonic acid (AA), resulting in an array of bioactive prostaglandins. However, much work has been done showing that COX-2 will perform this reaction on several different AA-containing molecules, most importantly, the endocannabinoid 2-arachidonoylglycerol (2-AG). The products of 2-AG oxygenation, prostaglandin glycerol esters (PG-Gs), are analogous to canonical prostaglandins.

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