title: Nicotinamide inhibits inducible nitric oxide synthase mRNA in primary rat glial cells.
abstract: Nitric oxide (NO) exerts cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of inducible NO synthase (iNOS), enhances neurotoxicity associated with the N-methyl-D-aspartate (NMDA) receptor. The present study examined whether nicotinamide, an inhibitor of poly (ADP-ribose) synthetase, inhibits NO formation in primary culture of rat glial cells. Nicotinamide (5-20 mM) suppressed iNOS mRNA expression and subsequent NO formation, which were induced by the combination of interferon-gamma and lipopolysaccharide, in a dose dependent manner. In addition, high-concentration (20 mM) nicotinamide decreased mRNA of interferon regulatory factor-1, a transcription factor which plays a major role in iNOS mRNA induction. These results suggest that nicotinamide may have protective effect on glial NO-related pathologies by preventing iNOS mRNA induction.
authors.affiliation: Department of Neurosurgery, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fujimura
authors.forename: T
authors.initials: T
authors.lastname: Tominaga
authors.forename: T
authors.initials: T
authors.lastname: Yoshimoto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009536:Niacinamide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D009573:Nitrites / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494259:Irf1 protein, rat; D008070:Lipopolysaccharides; D009573:Nitrites; D010750:Phosphoproteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; D009536:Niacinamide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase