Nicotinamide inhibits nitric oxide synthase mRNA induction in activated macrophages
- PMID: 7506533
- PMCID: PMC1137789
- DOI: 10.1042/bj2970053
Nicotinamide inhibits nitric oxide synthase mRNA induction in activated macrophages
Abstract
Nitric oxide (NO) is a potent mediator involved in many biological functions including inflammation and non-specific immunity. Murine macrophages possess the prototype of high-output NO synthase which is not constitutively expressed but induced within a few hours by immunological stimuli. In this study, we explored the possibility of controlling the activity of the inducible NO synthase by interfering with the transduction signal which triggers its induction, in the RAW 264.7 macrophage cell line. We found that nicotinamide, an inhibitor of ADP-ribosylation, prevented NO synthase induction in RAW 264.7 cells after stimulation with interferon gamma (IFN-gamma) and lipopolysaccharide (LPS). Furthermore, the level of NO synthase mRNA was measured by Northern-blot analysis and we found that nicotinamide prevents expression of NO synthase mRNA in IFN-gamma- and LPS-stimulated cells. Nicotinamide was also found to inhibit other macrophage functions expressed in response to IFN-gamma, i.e. tumour necrosis factor secretion and the expression of the Ia antigen of the major histocompatibility complex. Analysis of the pattern of ADP-ribosylated proteins revealed that nicotinamide as well as cholera toxin prevented the ADP-ribosylation of a 107-117 kDa protein found constitutively ADP-ribosylated in stimulated and non-stimulated macrophage extracts. Together, our results indicate ADP-ribosylation as a crucial point of the signalling pathway which leads to NO synthase mRNA induction.
Similar articles
-
Effects of inhibitors of ADP-ribosylation on macrophage activation.Adv Exp Med Biol. 1997;419:203-7. doi: 10.1007/978-1-4419-8632-0_25. Adv Exp Med Biol. 1997. PMID: 9193655
-
Protein kinase C and tyrosine kinase pathways regulate lipopolysaccharide-induced nitric oxide synthase activity in RAW 264.7 murine macrophages.Br J Pharmacol. 1995 Jan;114(2):482-8. doi: 10.1111/j.1476-5381.1995.tb13252.x. Br J Pharmacol. 1995. PMID: 7533621 Free PMC article.
-
Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide.J Biol Chem. 1993 Jan 25;268(3):1908-13. J Biol Chem. 1993. PMID: 7678412
-
Involvement of nitric oxide synthase in antiproliferative activity of macrophages: induction of the enzyme requires two different kinds of signal acting synergistically.Int J Immunopharmacol. 1994 May-Jun;16(5-6):401-6. doi: 10.1016/0192-0561(94)90028-0. Int J Immunopharmacol. 1994. PMID: 7523317 Review.
-
The role of nitric oxide in the pathogenesis of virus-induced encephalopathies.Curr Top Microbiol Immunol. 1995;196:51-6. doi: 10.1007/978-3-642-79130-7_6. Curr Top Microbiol Immunol. 1995. PMID: 7543399 Review. No abstract available.
Cited by
-
Newly discovered anti-inflammatory properties of the benzamides and nicotinamides.Mol Cell Biochem. 1999 Mar;193(1-2):119-25. Mol Cell Biochem. 1999. PMID: 10331648
-
Modulation of nitric oxide synthase activity in macrophages.Mediators Inflamm. 1995;4(2):75-89. doi: 10.1155/S0962935195000135. Mediators Inflamm. 1995. PMID: 18475620 Free PMC article.
-
NAD+ Degrading Enzymes, Evidence for Roles During Infection.Front Mol Biosci. 2021 Aug 16;8:697359. doi: 10.3389/fmolb.2021.697359. eCollection 2021. Front Mol Biosci. 2021. PMID: 34485381 Free PMC article. Review.
-
Diverse therapeutic efficacies and more diverse mechanisms of nicotinamide.Metabolomics. 2019 Oct 5;15(10):137. doi: 10.1007/s11306-019-1604-4. Metabolomics. 2019. PMID: 31587111 Review.
-
Modulation of inflammatory arthritis by inhibition of poly(ADP ribose) polymerase.Inflammation. 1995 Jun;19(3):379-87. doi: 10.1007/BF01534394. Inflammation. 1995. PMID: 7628865
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources