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Induction of Cyclooxygenase‐2 and Peroxisome Proliferator‐Activated Receptor‐γ during Nitric Oxide‐Induced Apoptotic PC12 Cell Death
Author(s) -
LIM SOYOUNG,
JANG JUNGHEE,
SURH YOUNGJOON
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.119
Subject(s) - nitric oxide , apoptosis , nitric oxide synthase , programmed cell death , peroxisome proliferator activated receptor , cyclooxygenase , sodium nitroprusside , chemistry , receptor , pharmacology , cytotoxicity , peroxisome , proinflammatory cytokine , inflammation , microbiology and biotechnology , biology , endocrinology , biochemistry , immunology , enzyme , in vitro
A bstract : 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 (δψ m ), cleavage of poly(ADP‐ribose) polymerase (PARP), and induction of p21 Waf1/Cip1 . It has been reported that the expression of cyclooxygenase‐2 (COX‐2) and peroxisome proliferator‐activated receptor‐γ (PPARγ) 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 PPARγ. Addition of the PPARγ antagonist GW9662 to the media augmented the NO‐induced cytotoxicity. Although cotreatment of PGE 2 (50 μM) 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 PPARγ may regulate the nitrosative stress‐induced apoptotic cell death.