title: L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis.
abstract: Methamphetamine (METH)-induced cell death contributes to the pathogenesis of neurotoxicity; however, the relative roles of oxidative stress, apoptosis, and autophagy remain unclear. L-Ascorbate, also called vitamin (Vit.) C, confers partial protection against METH neurotoxicity via induction of heme oxygenase-1. We further investigated the role of Vit. C in METH-induced oxidative stress, apoptosis, and autophagy in cortical cells. Exposure to lower concentrations (0.1, 0.5, 1 mM) of METH had insignificant effects on ROS production, whereas cells exposed to 5 mM METH exhibited ROS production in a time-dependent manner. We confirmed METH-induced apoptosis (by nuclear morphology revealed by Hoechst 33258 staining and Western blot showing the protein levels of pro-caspase 3 and cleaved caspase 3) and autophagy (by Western blot showing the protein levels of Belin-1 and conversion of microtubule-associated light chain (LC)3-I to LC3-II and autophagosome staining by monodansylcadaverine). The apoptosis as revealed by cleaved caspase-3 expression marked an increase at 18 h after METH exposure while both autophagic markers, Beclin 1 and LC3-II, marked an increase in cells exposed to METH for 6 and 24 h, respectively. Treating cells with Vit. C 30 min before METH exposure time-dependently attenuated the production of ROS. Vitamin C also attenuated METH-induced Beclin 1 and LC3-II expression and METH toxicity. Treatment of cells with Vit. C before METH exposure attenuated the expression of cleaved caspase-3 and reduced the number of METH-induced apoptotic cells. We suggest that the protective effect of Vit. C against METH toxicity might be through attenuation of ROS production, autophagy, and apoptosis.
authors.affiliation: Department of Nursing, Hsin Sheng Junior College of Medical Care and Management, Taoyuan, Taiwan.
authors.forename: Ya-Ni
authors.initials: YN
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Yang
authors.affiliation: Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan.
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Division of Orthopedics, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Chien-Cheng
authors.initials: CC
authors.lastname: Lai
authors.affiliation: Department of Neurosurgery, En Chu Kong Hospital, New Taipei City, Taiwan.
authors.forename: Chien-Tsai
authors.initials: CT
authors.lastname: Chiu
authors.affiliation: Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan. jywang2010@tmu.edu.tw.|Comprehensive Cancer Center, Taipei Medical University, Taipei, Taiwan. jywang2010@tmu.edu.tw.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000633:toxicity; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D008694:Methamphetamine / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D008694:Methamphetamine; D001205:Ascorbic Acid
keywords: Apoptosis; Ascorbate; Autophagy; Methamphetamine; Oxidative stress; Vitamin C