Importance of lipid rafts for lysophosphatidylcholine-induced caspase-1 activation and reactive oxygen species generation.
Lipid rafts play an important role in regulating cellular processes and functions. Here, we demonstrate that in microglia stimulated with the pro-inflammatory lipid lysophosphatidylcholine (LPC), caspase-1 activation and NADPH oxidase activity depend on intact lipid rafts. Disruption of lipid rafts with methyl-β-cyclodextrin, fumonisin B1 or nystatin prevented LPC-stimulated caspase-1 activation and reactive oxygen species (ROS) production, whereas LPC-induced Na(+) influx remained unaffected. Since ROS regulate caspase-1 activity in LPC-stimulated microglia, the effects of lipid raft-disrupting agents on caspase-1 activation can be related to their inhibition of NADPH oxidase-mediated ROS production.
Schilling
Tom
T
Division of Biomedical Sciences, St. George's University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
Eder
Claudia
C
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D037341:Fumonisins / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D017628:Microglia / Q000201:enzymology* / Q000648:ultrastructure; D019255:NADPH Oxidases / Q000378:metabolism; D009761:Nystatin / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000494:pharmacology
D037341:Fumonisins; D008244:Lysophosphatidylcholines; D017382:Reactive Oxygen Species; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D009761:Nystatin; C056933:fumonisin B1; D019255:NADPH Oxidases; D020170:Caspase 1