Effects of peroxisome proliferator-activated receptor agonists on LPS-induced neuronal death in mixed cortical neurons: associated with iNOS and COX-2.
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.
Kim
Eun Joo
EJ
Department of Physiology, School of Medicine, Ajou University, San 5, Woncheon-dong, Paldal-gu, Suwon 442-749, South Korea. eunjoo@madang.ajou.ac.kr
Kwon
Kyoung Ja
KJ
Park
Jee Young
JY
Lee
Soo Hwan
SH
Moon
Chang Hyun
CH
Baik
Eun Joo
EJ
D000818:Animals; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology; D002994:Clofibrate / Q000494:pharmacology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000032:analysis; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000187:drug effects* / Q000235:genetics; D008070:Lipopolysaccharides; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000235:genetics; D011453:Prostaglandins / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists* / Q000378:metabolism; D000077288:Troglitazone
D002839:Chromans; D007527:Isoenzymes; D008070:Lipopolysaccharides; D020025:Peroxisome Proliferators; D011453:Prostaglandins; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D009569:Nitric Oxide; C006253:pirinixic acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D002994:Clofibrate; D000077288:Troglitazone; D015232:Dinoprostone; C039671:ciglitazone