Sphingomyelinase but not ceramide induces nitric oxide synthase expression in rat brain microglia

Neurosci Lett. 2001 Sep 28;311(2):133-6. doi: 10.1016/s0304-3940(01)02162-0.

Abstract

Microglia, brain inflammatory cells, are activated in injured brain and function similar to macrophages. The activated microglia produce nitric oxide (NO), a major toxic substance from these cells, by inducing expression of inducible NO synthase (iNOS). In this study, we found that sphingomyelinase (SMase) alone induced NO release/iNOS mRNA expression in cultured rat brain microglia. On the contrary to SMase, however, membrane-permeable c2-ceramide had little effect on NO release/iNOS mRNA expression. Fumonisin B1, an inhibitor of de novo synthesis of ceramide, did not reduce lipopolysaccharide (LPS)-induced NO release. However, neither SMase nor c2-ceramide enhanced LPS- or Abeta (25-35)-induced NO release/iNOS mRNA expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Carboxylic Acids / pharmacology
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Fumonisins*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Lipopolysaccharides / pharmacology
  • Microglia / cytology
  • Microglia / enzymology*
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type II
  • Peptide Fragments / pharmacology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Sphingomyelin Phosphodiesterase / pharmacology*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Carboxylic Acids
  • Enzyme Inhibitors
  • Fumonisins
  • Lipopolysaccharides
  • N-acetylsphingosine
  • Peptide Fragments
  • RNA, Messenger
  • amyloid beta-protein (25-35)
  • fumonisin B1
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Sphingomyelin Phosphodiesterase
  • Sphingosine