S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
Induction of cyclooxygenase-2 and peroxisome proliferator-activated receptor-γ during nitric oxide-induced apoptotic PC12 cell death
- Lim, So‐Young; Jang, Jung‐Hee; Surh, Young‐Joon
- Issue Date
- Annals of the New York Academy of Sciences, Vol.1010, pp.648-658
- apoptosis; cyclooxygenase-2 (COX-2); nitric oxide; nitrosative stress; PC12 cells; peroxisome proliferator-activated receptor; (PPAR-gamma); prostaglandin E-2
- 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.
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