Cytoprotective Effect of 15-deoxy-Delta(12,14) Prostaglandin J2 (15d-PGJ2) against H2O2 Induced Death of Neuronally-differentiated PC12 Cells

J Korean Neurol Assoc > Volume 24(1); 2006 > Article

Journal of the Korean Neurological Association 2006;24(1): 58-65.

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

오동호, 고성호 정 부 박기형 김현영 송치원a 김영철 김주한 김명호 김승현

한양대학교 의과대학 신경과학교실, 식품의약품안전청 국립독성연구원 독성연구부 일반독성과a

Cytoprotective Effect of 15-deoxy-Delta(12,14) Prostaglandin J2 (15d-PGJ2) against H2O2 Induced Death of Neuronally-differentiated PC12 Cells

Dong-Ho Oh

Department of Neurology, College of Medicine, Hanyang University, Seoul; Department of General Toxicology, National Institute of Toxicological Research, KFDAa, Seoul, Korea

Abstract

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.