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Prostanoid synthesis in mammalian tissues is regulated at the level of prostaglandin H synthase (PGHS) cyclooxygenase catalysis by the availability and structure of substrate fatty acid and availability of peroxide activator. Two major PGHS isoforms, with distinct pathophysiological functions and catalytic regulation, have been characterized mammals; a functionally homologous PGHS isoform pair has been cloned from an evolutionarily distant vertebrate, brook trout. The cyclooxygenase activities of recombinant brook trout PGHS-1 and -2 were characterized to test the generality of mammalian regulatory paradigms for substrate specificity, peroxide activation, and product shifting by aspirin. Both cyclooxygenases had much more restrictive substrate specificities than their mammalian counterparts, pronounced discrimination toward arachidonate 4n-6) and against eicosapentaenoate (20:5n-3) and docosahexaenoate (22:6n-3), the latter two prominent trout tissue lipids. Aspirin treatment did not increase lipoxygenase-type catalysis by either trout enzyme. trout enzymes had higher requirements for peroxide activator than their mammalian counterparts, though the preferential peroxide activation of PGHS-2 PGHS-1 seen in mammals was conserved in the enzymes. The divergence in cyclooxygenase characteristics between the trout and mammalian PGHS proteins may reflect accomodations to differences among vertebrates in tissue lipid composition and general redox state. [ABSTRACT FROM AUTHOR]

Objective: Very recently, petaslignolide A, corresponding to 9-hydroxypinoresinol(9-HP) glycoside from butterbur, traditional vegetable, was observed to show a remarkable neuroprotective effect through antioxidant action in brain tissue, in contrast to a negligible neuroprotection by pinoresinol glycoside. The aim of present study is to assess the neuroprotective action of 9-HP against oxidative damage in the brain of mice treated with kainic acid(KA), and to examine the mode by which 9-HP demonstrates neuroprotective action. Methods: Male ICR mice were administered i.p. with 9-HP before KA injection.. Biomarkers of oxidative stress for the biochemical, neurobehavioral, morphological evaluations were analyzed. Results: A remarkable neuroprotection was observed with a single administration (30 mg/kg) of 9-HP 24 h, but not 2 h, before KA challenge. Furthermore, 9-HP (20 mg/kg), administered for 3 days before KA challenge, reduced the lethality (60 %) induced by KA to none, and remarkably alleviated behavioral signs of KA neurotoxicity. Additionally, 9-HP pretreatment prevented the decrease in total glutathione (GSH) and TBARS. Furthermore, GSH-peroxidase activity in brain tissue was restored to control level. Conclusion: From these results, it is proposed that 9-HP exerts a potent neuroprotection mainly by preventing oxidative stress in brain tissue of mice challenged with KA. [ABSTRACT FROM AUTHOR]