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L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis.
Mol Neurobiol. 2017 01; 54(1):125-136.MN

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+Show Affiliations

Department of Nursing, Hsin Sheng Junior College of Medical Care and Management, Taoyuan, Taiwan.Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan.Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan.Division of Orthopedics, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan.Department of Neurosurgery, En Chu Kong Hospital, New Taipei City, Taiwan.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26732595

Citation

Huang, Ya-Ni, et al. "L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells Via Inhibiting Oxidative Stress, Autophagy, and Apoptosis." Molecular Neurobiology, vol. 54, no. 1, 2017, pp. 125-136.
Huang YN, Yang LY, Wang JY, et al. L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis. Mol Neurobiol. 2017;54(1):125-136.
Huang, Y. N., Yang, L. Y., Wang, J. Y., Lai, C. C., Chiu, C. T., & Wang, J. Y. (2017). L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis. Molecular Neurobiology, 54(1), 125-136. https://doi.org/10.1007/s12035-015-9561-z
Huang YN, et al. L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells Via Inhibiting Oxidative Stress, Autophagy, and Apoptosis. Mol Neurobiol. 2017;54(1):125-136. PubMed PMID: 26732595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis. AU - Huang,Ya-Ni, AU - Yang,Ling-Yu, AU - Wang,Jing-Ya, AU - Lai,Chien-Cheng, AU - Chiu,Chien-Tsai, AU - Wang,Jia-Yi, Y1 - 2016/01/05/ PY - 2015/07/07/received PY - 2015/11/29/accepted PY - 2016/1/7/pubmed PY - 2018/2/10/medline PY - 2016/1/7/entrez KW - Apoptosis KW - Ascorbate KW - Autophagy KW - Methamphetamine KW - Oxidative stress KW - Vitamin C SP - 125 EP - 136 JF - Molecular neurobiology JO - Mol Neurobiol VL - 54 IS - 1 N2 - 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. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/26732595/L_Ascorbate_Protects_Against_Methamphetamine_Induced_Neurotoxicity_of_Cortical_Cells_via_Inhibiting_Oxidative_Stress_Autophagy_and_Apoptosis_ L2 - https://dx.doi.org/10.1007/s12035-015-9561-z DB - PRIME DP - Unbound Medicine ER -