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(Arylthio)cyclopentenones derivatives prevent glutamate-induced HT22 cell death through a PPAR gamma-dependent
Shoko Shibata1, Kyoji Furuta, Masahide Maeda
1Department of Biomolecular Science, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan.
Abstract:
We show that cyclopentenone derivatives, which are synthetic analogs of cyclopentenone prostaglandins, are neuroprotective against glutamate-induced oxidative stress in HT22 cells. This effect was antagonized by a peroxisome proliferator-activated receptor-gamma (PPAR gamma) antagonist, T0070907. Pull-down assays revealed that biotinylated (arylthio)cyclopentenone (GIF-0643-biotin) and other biotin-bound cyclopentenones bind to PPAR gamma. The results also indicate that the GIF-0643-biotin-PPAR gamma complex is localized to the nucleus. Moreover, retinoid X receptor-alpha (RXR) co-precipitated with the GIF-0643-biotin-PPAR gamma complex, indicating that (arylthio)cyclopentenone can activate PPAR gamma-RXR heterodimers. These findings suggest that (arylthio)cyclopentenone derivatives prevent excitotoxicity by modulating gene expression via activation of the PPAR gamma-RXR hetrodimer.
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