신경세포로 분화된 PC12 세포의 과산화수소에 의한 손상에 대한 15-deoxy-D12,14-Prostagladin J2 (15d-PGJ2)의 세포보호효과

초록

Background: Neurodegenerative diseases are associated with oxidative stress. Antioxidants including 15-deoxy- Delta (12,14) prostaglandin J2 (15d-PGJ2) have been tried as potential therapeutic regimens of the experimental model of neurodegenerative disease. In this study, we investigated the neuroprotective role of 15d-PGJ2 on cytochrome c mediated apoptotic signals in oxidative stress injured neuronally-differentiated PC12 cells (nPC12 cells) by exposing them to H2O2. Methods: Following 100 µM H2O2 exposure, the viability of nPC12 cells (pretreated with 15d-PGJ2 vs. not pretreated) was evaluated by using MTT assay. Immunoreactivity (IR) of cytochrome c, caspase-3, and poly (ADP-ribose) polymerase (PARP) was examined by using a Western blot. Results: In this study, 15d-PGJ2 pretreated nPC12 cells showed an increase in cell viability until the concentrations of 15d-PGJ2 reached up to 4 µM, but there was no increment of cell viability in higher concentrations. The inhibition of cytochrome c release, activation of caspase-3, and cleavage of PARP were demonstrated by the pretreatment of 15d-PGJ2 up to 4 µM. However, these were not observed in the pretreatment with 8 µM 15d-PGJ2. Conclusions: These data show that 15d-PGJ2 affects the apoptotic pathway through downstream signals including cytochrome c and caspase-3 pathway. Therefore, these results suggest that 15d-PGJ2 could be a new potential therapeutic candidate for the oxidative stress-injury model of neurodegenerative diseases.

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