Nitric oxide: a prostaglandin H synthase 1 and 2 reducing cosubstrate that does not stimulate cyclooxygenase activity or prostaglandin H synthase expression in murine macrophages. Arch Biochem Biophys 1996 Nov 15;335(2):369-76
Date
11/15/1996Pubmed ID
8914934DOI
10.1006/abbi.1996.0518Scopus ID
2-s2.0-0030588938 (requires institutional sign-in at Scopus site) 63 CitationsAbstract
Several recent reports have investigated the possibility that nitric oxide (-NO) can regulate prostaglandin H synthase (PHS) activity. The potential significance of -NO regulation of PHS is considerable, when one considers the numerous important biological processes that are influenced by PHS. In this study, we used microsomal and purified PHS to investigate the direct effect of -NO and -NO-generating compounds on PHS catalytic activity. We found that -NO neither significantly inhibited nor enhanced prostaglandin (PG) formation, despite the fact that -NO stimulated PHS peroxidase activity. We also investigated the effect of -NO and -NO generators on PHS product, protein, and mRNA levels in the RAW264.7 murine macrophage cell line. We found that -NO or -NO generators had little or no effect on PG formation, PHS expression, or PHS mRNA expression in unstimulated RAW264.7 cells. The same results were obtained with macrophages that were stimulated by 18 h pretreatment with lipopolysaccharide, a known inducer of PHS-2 in macrophages. These data clearly indicate that -NO acts as a cosubstrate for PHS peroxidase. However, -NO does not enhance or inhibit either cyclooxygenase activity or expression of PHS in the model systems used in this study.
Author List
Curtis JF, Reddy NG, Mason RP, Kalyanaraman B, Eling TEAuthor
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Line
Lipopolysaccharides
Macrophages
Mice
Nitric Oxide
Peroxidases
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Substrate Specificity