Ginsenoside Re Protects Methamphetamine-Induced Mitochondrial Burdens And Proapoptosis Via Genetic Inhibition Of Protein Kinase C Delta In Human Neuroblastoma Dopaminergic Sh-Sy5y Cell Lines

Recently, we have demonstrated that ginsenoside Re protects methamphetamine (MA)-induced dopaminergic toxicity in mice via genetic inhibition of PKC delta and attenuation of mitochondrial stress. In addition, we have reported that induction of mitochondrial glutathione peroxidase (GPx) is also important for neuroprotection mediated by ginsenoside Re. To extend our knowledge, we examined the effects of ginsenoside Re against MA toxicity in vitro condition using SH-SY5Y neuroblastoma cells. Treatment with ginsenoside Re resulted in significant attenuations against a decrease in the activity of GPx and an increase in the activity of superoxide dismutase (SOD) in the cytosolic and mitochondrial fraction. The changes in glutathione (GSH) paralleled those in GPx in the same experimental condition. Consistently, ginsenoside Re treatment exhibited significant protections against cytosolic and mitochondrial oxidative damage (i.e. lipid peroxidation and protein oxidation), mitochondrial translocation of PKC delta, mitochondrial dysfunction (mitochondrial transmembrane potential and intra-mitochondrial Ca2+), apoptotic events [i.e., cytochrome c release from mitochondria, cleavage of caspase-3 and poly (ADP-ribose) polymerase-1, nuclear condensation, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells], and a reduction in the tyrosine hydroxylase (TH) expression and TH activity induced by MA in SH-SY5Y neuroblastoma cells. These protective effects of ginsenoside Re were comparable to those of PKC delta antisense oligonucleotide (ASO). However, ginsenoside Re did not significantly provide additional protective effects mediated by genetic inhibition of PKC delta. Our results suggest that PKC delta is a specific target for ginsenoside Re-mediated protective activity against MA toxicity in SH-SY5Y neuroblastoma cells. Copyright (C) 2014 John Wiley & Sons, Ltd.