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Induction of cyclooxygenase-2 and peroxisome proliferator-activated receptor-γ during nitric oxide-induced apoptotic PC12 cell death : Induction of cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma during nitric oxide-induced apoptotic PC12 cell death

Cited 9 time in Web of Science Cited 11 time in Scopus
Authors

Lim, So‐Young; Jang, Jung‐Hee; Surh, Young‐Joon

Issue Date
2003-12
Publisher
New York Academy of Sciences
Citation
Annals of the New York Academy of Sciences, Vol.1010, pp.648-658
Abstract
Inappropriate expression of inducible nitric oxide synthase (iNOS) and unregulated production of nitric oxide (NO) may contribute to neuronal cell death implicated in neurological disorders such as Alzheimer's disease. In this study, we have investigated the molecular mechanisms underlying nitrosative cell death induced by NO in cultured rat pheochromocytoma (PC12) cells. Incubation of PC12 cells with the NO donor sodium nitroprusside (SNP) resulted in apoptotic death as revealed by the decrease of mitochondrial transmembrane potential (DeltaPsi(m)), cleavage of poly(ADP-ribose) polymerase (PARP), and induction of p21(Wafl/Cip1). It has been reported that the expression of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor-gamma (PPARgamma) is elevated in Alzheimer's disease, and certain nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk and delay the onset of Alzheimer's disease. Treatment of PC12 cells with a proapoptotic dose of SNP induced expression of both COX-2 and PPARgamma. Addition of the PPARgamma antagonist GW9662 to the media augmented the NO-induced cytotoxicity. Although cotreatment of PGE(2) (50 muM) and SNP (0.4 mM) aggravated the NO-induced cytotoxicity, preincubation of the same concentration of PGE(2) was cytoprotective. Taken together, the above findings suggest that the proinflammatory mediators such as PGE(2) and PPARgamma may regulate the nitrosative stress-induced apoptotic cell death.
ISSN
0077-8923
URI
https://hdl.handle.net/10371/172871
DOI
https://doi.org/10.1196/annals.1299.119
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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