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Effects of peroxisome proliferator-activated receptor agonists on LPS-induced neuronal death in mixed cortical neurons: associated with iNOS and COX-2.

Kim, EJ; Kwon, KJ; Park, JY; Lee, SH; Moon, CH; Baik, EJ
Brain research, 941(1-2):1-10, 2002
Journal Title
Brain research
In neurodegenerative disease, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been regarded as beneficial. The NSAID, an inhibitor of cyclooxygenase (COX), has been also suggested as a ligand of the peroxisome proliferator-activated receptor (PPAR). In cortical neuron-glial co-cultures, we examined the effect of PPAR agonists on lipopolysaccharide(LPS)-induced neuronal death, which has been known to be NO-dependent. LPS induced iNOS expression and the release of nitric oxide in microglia, and COX-2 expression in neurons. PPAR-gamma agonists such as 15d-PGJ(2), ciglitazone and troglitazone prevented LPS-induced neuronal death and abolished LPS-induced NO and PGE(2) release, however PPAR-alpha agonists such as clofibrate and WY14,643 did not produce the same results. PPAR-gamma agonists also reduced LPS-induced iNOS and COX-2 expression, which suggested by interfering with the NF-kappaB signal pathway.
MeSH terms
AnimalsCell Culture TechniquesCell Death/*drug effectsChromans/pharmacologyClofibrate/pharmacologyCyclooxygenase 2Dinoprostone/analysisElectrophoretic Mobility Shift AssayEscherichia coliImmunohistochemistryIn Situ Nick-End LabelingIsoenzymes/*drug effects/geneticsLipopolysaccharidesMiceMice, Inbred ICRNeurons/*drug effects/metabolismNitric Oxide/analysisNitric Oxide Synthase/*drug effects/geneticsNitric Oxide Synthase Type IIPeroxisome Proliferators/*pharmacologyProstaglandin-Endoperoxide Synthases/*drug effects/geneticsProstaglandins/pharmacologyPyrimidines/pharmacologyReceptors, Cytoplasmic and Nuclear/*agonists/metabolismReverse Transcriptase Polymerase Chain ReactionThiazoles/pharmacology*ThiazolidinedionesTranscription Factors/*agonists/metabolism
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Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
이, 수환문, 창현백, 은주
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