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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Marnett, L. J. Morrow, J. D. Crews, B. C. Timmons, M. D. Landino, L. M. |
| Description | Author Affiliation: Landino LM ( Department of Biochemistry, A.B. Hancock, Jr., Memorial Laboratory for Cancer Research, Vanderbilt Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 26 |
| Volume Number | 93 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1996-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Glutathione Peroxidase Metabolism Nitrates Pharmacology Nitric Oxide Prostaglandin-Endoperoxide Synthases Prostaglandins Biosynthesis Superoxides Animals Arachidonic Acid Cell Line Enzyme Activation Kinetics Macrophages Metalloporphyrins Molsidomine Analogs & Derivatives Chemical Synthesis Chemistry Nitric Oxide Synthase Salicylates Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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