Lipopolysaccharide stimulates the secretion of the amyloid precursor protein via a protein kinase C-mediated pathway.
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.
Small
Claire I
CI
Alzheimer's Disease Research Centre, Division of Pathology and Neurosciences, University of Dundee Medical School, Ninewells Hospital, Dundee DD1 9SY, UK.
Lyles
Geoffrey A
GA
Breen
Kieran C
KC
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D007211:Indoles; D008070:Lipopolysaccharides; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D011493:Protein Kinase C; C070515:bisindolylmaleimide I