Differential modulation of prostaglandin H synthase-2 by nitric oxide-related species in intact cells

A. S. Vidwans, T. F. Uliasz, J. A. Hewett, S. J. Hewett

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22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11533-11542
Number of pages10
JournalBiochemistry
Volume40
Issue number38
DOIs
StatePublished - Sep 25 2001

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ASJC Scopus subject areas

  • Biochemistry

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