Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis.

Landino LM, Crews BC, Timmons MD, Morrow JD, Marnett LJ
Proc Natl Acad Sci U S A. 1996 93 (26): 15069-74

PMID: 8986765 · PMCID: PMC26357 · DOI:10.1073/pnas.93.26.15069

Peroxynitrite activates the cyclooxygenase activities of constitutive and inducible prostaglandin endoperoxide synthases by serving as a substrate for the enzymes' peroxidase activities. Activation of purified enzyme is induced by direct addition of peroxynitrite or by in situ generation of peroxynitrite from NO coupling to superoxide anion. Cu,Zn-superoxide dismutase completely inhibits cyclooxygenase activation in systems where peroxynitrite is generated in situ from superoxide. In the murine macrophage cell line RAW264.7, the lipophilic superoxide dismutase-mimetic agents, Cu(II) (3,5-diisopropylsalicylic acid)2, and Mn(III) tetrakis(1-methyl-4-pyridyl)porphyrin dose-dependently decrease the synthesis of prostaglandins without affecting the levels of NO synthase or prostaglandin endoperoxide synthase or by inhibiting the release of arachidonic acid. These findings support the hypothesis that peroxynitrite is an important modulator of cyclooxygenase activity in inflammatory cells and establish that superoxide anion serves as a biochemical link between NO and prostaglandin biosynthesis.

MeSH Terms (16)

Animals Arachidonic Acid Cell Line Enzyme Activation Glutathione Peroxidase Kinetics Macrophages Metalloporphyrins Molsidomine Nitrates Nitric Oxide Nitric Oxide Synthase Prostaglandin-Endoperoxide Synthases Prostaglandins Salicylates Superoxides

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