title: Ginsenoside Re protects methamphetamine-induced mitochondrial burdens and proapoptosis via genetic inhibition of protein kinase C δ in human neuroblastoma dopaminergic SH-SY5Y cell lines.
abstract: Recently, we have demonstrated that ginsenoside Re protects methamphetamine (MA)-induced dopaminergic toxicity in mice via genetic inhibition of PKCδ 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 PKCδ, mitochondrial dysfunction (mitochondrial transmembrane potential and intra-mitochondrial Ca(2+)), 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 PKCδ antisense oligonucleotide (ASO). However, ginsenoside Re did not significantly provide additional protective effects mediated by genetic inhibition of PKCδ. Our results suggest that PKCδ is a specific target for ginsenoside Re-mediated protective activity against MA toxicity in SH-SY5Y neuroblastoma cells.
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 200-701, Republic of Korea.
authors.forename: Yunsung
authors.initials: Y
authors.lastname: Nam
authors.affiliation: School of Veterinary Medicine, Kangwon National University, Chunchon, 200-701, Republic of Korea.
authors.forename: Myung Bok
authors.initials: MB
authors.lastname: Wie
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 200-701, Republic of Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Shin
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 200-701, Republic of Korea.
authors.forename: Thuy-Ty Lan
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Ginseng Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, 143-701, Republic of Korea.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.affiliation: Department of Oriental Medical Food & Nutrition, Semyung University, Jecheon, 390-711, Republic of Korea.
authors.forename: Sung Kwon
authors.initials: SK
authors.lastname: Ko
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 156-756, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 200-701, Republic of Korea.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects*; D045744:Cell Line, Tumor; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051745:Protein Kinase C-delta / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D000697:Central Nervous System Stimulants; D036145:Ginsenosides; D018696:Neuroprotective Agents; D008694:Methamphetamine; C049864:ginsenoside Re; D045304:Cytochromes c; D014446:Tyrosine 3-Monooxygenase; D051745:Protein Kinase C-delta
keywords: apoptosis; ginsenoside Re; glutathione; glutathione peroxidase; methamphetamine; mitochondria; oxidative damage; tyrosine hydroxylase