Nicotinamide inhibits inducible nitric oxide synthase mRNA in primary rat glial cells.
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.
Fujimura
M
M
Department of Neurosurgery, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
Tominaga
T
T
Yoshimoto
T
T
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
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