Protective effects of Debo on serum-deprived apoptosis of PC12 cells via inhibition of H2O2 generation and caspase 3-like protease activity.
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-kappaB 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-kappaB 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.
Lee
Jienny
J
Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Chonbuk, South Korea.
Kim
Myung-Sunny
MS
Park
Channy
C
Lim
Yun-Sook
YS
Lee
In
I
Moon
Byung-Soon
BS
Lee
Ho-Sub
HS
Park
Raekil
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats
D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D016328:NF-kappa B; D010936:Plant Extracts; D006861:Hydrogen Peroxide; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione