Differential modulation of prostaglandin H synthase-2 by nitric oxide-related species in intact cells
| Autor: | Aniruddha S. Vidwans, James A. Hewett, Sandra J. Hewett, Tracy F. Uliasz |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Lipopolysaccharides
Prostaglandin Nitric Oxide Synthase Type II S-Nitroso-N-Acetylpenicillamine Transfection Biochemistry Dinoprostone Gene Expression Regulation Enzymologic Nitric oxide chemistry.chemical_compound Mice Biosynthesis Chlorocebus aethiops Protein biosynthesis Animals Nitric Oxide Donors Cells Cultured Regulation of gene expression Chemistry Penicillamine Brain Isoenzymes Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Astrocytes Molsidomine COS Cells S-Nitroso-N-acetylpenicillamine Nitric Oxide Synthase Oxidation-Reduction Peroxynitrite Nitroso Compounds |
| Zdroj: | Biochemistry. 40(38) |
| ISSN: | 0006-2960 |
| Popis: | Nitrogen monoxide (NO) has been reported to both activate and inhibit prostaglandin (PG) biosynthesis. This apparent paradox might be explained by the production/action of distinct NO-related species formed as a result of the prevailing redox states of different cellular systems. As such, the effect of NO donors with different redox characteristics on the modulation of prostaglandin H synthase-2 (PGHS-2) in primary mouse cortical astrocytes and COS-7 cells engineered to overexpress PGHS-2 was assessed. In general, compounds that released NO(*) or NO(-) enhanced, while a peroxynitrite (OONO(-)) generator inhibited, PGHS-2-dependent prostaglandin production. While the possibility of altered gene transcription was eliminated in the COS-7 system as PGHS-2 was maximally expressed, in primary astrocytes where PGHS-2 expression was induced by lipopolysaccharide (LPS), effects on protein expression were detected. Compounds that released NO(*) synergistically enhanced LPS-mediated PGHS-2 protein synthesis. None of these effects were mediated by cGMP. All donors lost their ability to modulate PGHS-2 expression and function when decayed. These results indicate that the ultimate effect of NO on PGHS-2 enzyme activity and expression is dictated by the prevalent NO-related species formed, suggesting that important interactions which may exist between NO and prostanoid pathways in vivo will be highly dependent on the inherent redox environment. |
| Databáze: | OpenAIRE |
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