Ginsenoside Re protects methamphetamine-induced dopaminergic neurotoxicity via modulating PKC delta gene

Abstract

Event Abstract Back to Event Ginsenoside Re protects methamphetamine-induced dopaminergic neurotoxicity via modulating PKC delta gene Eun-Joo Shin1, Sung Kwon Ko2, Ji Hoon Jeong3, Choon-Gon Jang4 and Hyoung-Chun Kim1* 1 Kangwon National University, Neuropsychopharmacology & Toxicology Program, College of Pharmacy, Korea, South 2 Semyung University, Department of Oriental Medical Food & Nutrition, Republic of Korea 3 Chung-Ang University, Department of Pharmacology, College of Medicine, Korea, South 4 Sungkyunkwan University, Department of Pharmacology, School of Pharmacy, Republic of Korea 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 Re significantly attenuated MA-induced dopaminergic degeneration in vivo by inhibiting impaired enzymatic antioxidant systems, mitochondrial oxidative stress, mitochondrial translocation of PKCδ, 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 Re did not provide any additional protective effects in the presence of PKCδ inhibition. We also examined effects of Re against MA toxicity in the SH-SY5Y neuroblastoma cells. Treatment with Re resulted in significant attenuations against decrease in the activity of glutathione peroxidase (GPx) and increase in the activity of superoxide dismutase (SOD) in the cytosolic and mitochondrial fraction. The changes in GSH paralleled those in GPx. Re treatment exhibited significant protections against mitochondrial oxidative damage, mitochondrial translocation of PKCδ, mitochondrial dysfunction, apoptotic events, and a reduction in the tyrosine hydroxylase (TH) expression and TH activity induced by MA. These protective effects of Re were comparable to those of PKCδ antisense oligonucleotide (ASO). However, Re did not significantly provide additional protective effects mediated by genetic inhibition of PKCδ in SH-SY5Y neuroblastoma cells. Our results suggest that PKCδ is a critical target for ginsenoside Re-mediated protective activity in response to dopaminergic degeneration induced by MA in vivo and in vitro. Acknowledgements This study is supported by a grant (Project No.S111415L020100) of the ‘Forestry Technology Projects’ provided by the Korea Forest Service, and in part by a grant (14182MFDS979) from the Korea Food and Drug Administration, Republic of Korea. Keywords: Methamphetamine, Superoxide Dismutase, antioxidant, ginseng, neuroblastoma cells Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Symposium 5: Boosting Brain Function with Nutraceuticals: What is the Evidence and how might they Work Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Shin E, Ko S, Jeong J, Jang C and Kim H (2016). Ginsenoside Re protects methamphetamine-induced dopaminergic neurotoxicity via modulating PKC delta gene. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00023 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Jul 2016; Published Online: 11 Aug 2016. * Correspondence: Prof. Hyoung-Chun Kim, Kangwon National University, Neuropsychopharmacology & Toxicology Program, College of Pharmacy, Chunchon, Kangwon-do, Korea, South, kimhc@kangwon.ac.kr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Eun-Joo Shin Sung Kwon Ko Ji Hoon Jeong Choon-Gon Jang Hyoung-Chun Kim Google Eun-Joo Shin Sung Kwon Ko Ji Hoon Jeong Choon-Gon Jang Hyoung-Chun Kim Google Scholar Eun-Joo Shin Sung Kwon Ko Ji Hoon Jeong Choon-Gon Jang Hyoung-Chun Kim PubMed Eun-Joo Shin Sung Kwon Ko Ji Hoon Jeong Choon-Gon Jang Hyoung-Chun Kim Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.