title: Ginsenoside Re rescues methamphetamine-induced oxidative damage, mitochondrial dysfunction, microglial activation, and dopaminergic degeneration by inhibiting the protein kinase Cδ gene.
abstract: Ginsenoside Re, one of the main constituents of Panax ginseng, possesses novel antioxidant and anti-inflammatory properties. However, the pharmacological mechanism of ginsenoside Re in dopaminergic degeneration remains elusive. We suggested that protein kinase C (PKC) δ mediates methamphetamine (MA)-induced dopaminergic toxicity. Treatment with ginsenoside Re significantly attenuated methamphetamine-induced dopaminergic degeneration in vivo by inhibiting impaired enzymatic antioxidant systems, mitochondrial oxidative stress, mitochondrial translocation of protein kinase Cδ, mitochondrial dysfunction, pro-inflammatory microglial activation, and apoptosis. These protective effects were comparable to those observed with genetic inhibition of PKCδ in PKCδ knockout (-/-) mice and with PKCδ antisense oligonucleotides, and ginsenoside Re did not provide any additional protective effects in the presence of PKCδ inhibition. Our results suggest that PKCδ is a critical target for ginsenoside Re-mediated protective activity in response to dopaminergic degeneration induced by MA.
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.forename: Seung Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: Thuy-Ty Lan
authors.initials: TT
authors.lastname: Nguyen
authors.forename: Dae Hun
authors.initials: DH
authors.lastname: Park
authors.forename: Myung-Bok
authors.initials: MB
authors.lastname: Wie
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.forename: Byung Wook
authors.initials: BW
authors.lastname: Yang
authors.forename: Sung Kwon
authors.initials: SK
authors.lastname: Ko
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D036145:Ginsenosides; D047428:Protein Kinase Inhibitors; D008694:Methamphetamine; C049864:ginsenoside Re; D051745:Protein Kinase C-delta