| 15-Deoxy-Δ12,14-prostaglandin J2: The endogenous electrophile that induces neuronal apoptosis | |
Abstract/OtherAbstract
:
|
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-Δ12,14-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. |
Authors
:
|
Kondo, Mitsuhiro, Shibata, Takahiro, Kumagai, Takeshi, Osawa, Toshihiko, Shibata, Noriyuki, Kobayashi, Makio, Sasaki, Shoichi, Iwata, Makoto, Noguchi, Noriko, Uchida, Koji |
Related Documents
:
|
0036618605 - Regulation of apoptosis by adenovirus type 5 0001096805 - Effects of xenoestrogens on t lymphocytes: modulation of bcl-2, p53, and apoptosis 0001555985 - Preliminary results on the effects of cd40/cd40l interactions and sac-induction on ifn-... 0034650005 - Cytokines and cells online pathfinder encyclopaedia : cope, version 22.6 |
Contributors
:
|
- |
Publication Detail
:
|
Publisher : The National Academy of Sciences Type : Text Format : - |
Date Detail
:
|
- |
Subject
:
|
Biological Sciences |
Coverage
:
|
- |
Relation
:
|
- |
Source
:
|
- |
Copyright Information
:
|
Copyright © 2002, The National Academy of Sciences |
Other Details
:
|
Languages : en |
Export Citation
:
|
APA/MLA Format Download EndNote Download BibTex |
Previous Document: Agonist-induced PIP2 Hydrolysis Inhibits Cortical Actin Dynamics: Regulation at a Global but not at ...
Next Document: A core–BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific gene...