文章基本信息

标题：15-Deoxy-Δ12,14-prostaglandin J2: The endogenous electrophile that induces neuronal apoptosis
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作者：Mitsuhiro Kondo ; Takahiro Shibata ; Takeshi Kumagai 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：11
页码：7367-7372
DOI：10.1073/pnas.112212599
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Prostaglandin D2 (PGD2), a major cyclooxygenase product in a variety of tissues and cells, readily undergoes dehydration to yield the bioactive cyclopentenone-type PGs of the J2-series, such as 15-deoxy-{Delta}12,14-PGJ2 (15d-PGJ2). The observation that the level of 15d-PGJ2 increased in the tissue cells from patients with sporadic amyotrophic lateral sclerosis suggested that the formation of 15d-PGJ2 may be closely associated with neuronal cell death during chronic inflammatory processes. In vitro experiments using SH-SY5Y human neuroblastoma cells revealed that 15d-PGJ2 induced apoptotic cell death. An oligonucleotide microarray analysis demonstrated that, in addition to the heat shock-responsive and redox-responsive genes, the p53-responsive genes, such as gadd45, cyclin G1, and cathepsin D, were significantly up-regulated in the cells treated with 15d-PGJ2. Indeed, the 15d-PGJ2 induced accumulation and phosphorylation of p53, which was accompanied by a preferential redistribution of the p53 protein in the nuclei of the cells and by a time-dependent increase in p53 DNA binding activity, suggesting that p53 accumulated in response to the treatment with 15d-PGJ2 was functional. The 15d-PGJ2-induced accumulation of p53 resulted in the activation of a death-inducing caspase cascade mediated by Fas and the Fas ligand.