Lipopolysaccharide stimulates the secretion of the amyloid precursor protein via a protein kinase C-mediated pathway

Neurobiol Dis. 2005 Aug;19(3):400-6. doi: 10.1016/j.nbd.2005.01.013.


The processing of the amyloid precursor protein (APP) by the secretase family of protease enzymes can be influenced by a variety of diverse factors, including elements of the immune response. In this study, we have investigated the effect of the pro-inflammatory lipopolysaccharide (LPS) on APP processing in rat glial cell cultures derived from both cortex and cerebellum. LPS activation of the cells, as monitored by the induction of the pro-inflammatory nitric oxide synthase (iNOS) enzyme, elicited no change in the overall cellular expression levels of APP, although there was a marked concentration-related increase in the secretion of the soluble APPs following both short- (4 h) and long-term (18 h) drug treatment times. The stimulation of APPs secretion was blocked by the protein kinase C (PKC) inhibitor GF109203x, suggesting that LPS may act via a PKC-mediated pathway to increase APPs secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Cerebellum / drug effects
  • Cerebral Cortex / drug effects
  • Dose-Response Relationship, Drug
  • Immunoblotting
  • Indoles / pharmacology
  • Lipopolysaccharides / pharmacology*
  • Maleimides / pharmacology
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Nitric Oxide Synthase / drug effects
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Protein Kinase C / drug effects*
  • Protein Kinase C / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Rats
  • Rats, Wistar
  • Time Factors


  • Amyloid beta-Protein Precursor
  • Indoles
  • Lipopolysaccharides
  • Maleimides
  • Protein Kinase Inhibitors
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Protein Kinase C
  • bisindolylmaleimide I