PROTECTIVE EFFECTS OF DEBO ON SERUM-DEPRIVED APOPTOSIS OF PC12 CELLS VIA INHIBITION OF H₂O₂ GENERATION AND CASPASE 3-LIKE PROTEASE ACTIVITY

ABSTRACT

Oxidative stress can be induced neurotoxic insults by increasing intracellular H₂O₂, which has been implicated in various neurodegenerative diseases in aging. We investigated the mechanism by which Debo protects PC12 cells from serum deprivation-induced apoptosis. PC12 cells underwent apoptotic death in association with increase in caspase 3-like activity, DNA fragmentation, H₂O₂ production, GSH depletion, and NF-κB activation after 24 hr of serum withdrawal. Debo protected cells from a serum deprivation-induced cytotoxicity in a dose dependent manner. Debo recovered the intracellular GSH level decreased by serum deprivation in PC12 cells. Also, Debo inhibited the activation of caspase 3-like protease of serum-deprived PC12 cells in a dose dependent manner. Furthermore, Debo inhibited the transcriptional activation of NF-κB by serum deprivation. These findings indicate that Debo may protect PC12 cells against apoptosis by serum deprivation via generation of intracellular GSH to scavenge oxidative radicals including H₂O₂.