J Korean Neurol Assoc.  2006 Feb;24(1):58-65.

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

• Oh DH
• Koh SH
• Chung B
• Park KH
• Kim HY
• Song CW
• Kim Y
• Kim J
• Kim MH
• Kim SH

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 micor M 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 micor M, 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 micor M. However, these were not observed in the pretreatment with 8 micor M 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.

Keyword

Apoptosis; Neurodegenerative disease; Antioxidants; Cytochrome c; Caspase-3

MeSH Terms

Animals
Antioxidants
Apoptosis
Blotting, Western
Caspase 3
Cell Survival
Cytochromes c
Models, Theoretical
Neurodegenerative Diseases
Oxidative Stress
PC12 Cells*
Antioxidants
Caspase 3
Cytochromes c