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Mol Neurobiol. 2017 Jan;54(1):125-136. doi: 10.1007/s12035-015-9561-z. Epub 2016 Jan 5.

L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis.

Author information

1
Department of Nursing, Hsin Sheng Junior College of Medical Care and Management, Taoyuan, Taiwan.
2
Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan.
3
Division of Orthopedics, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
4
Department of Neurosurgery, En Chu Kong Hospital, New Taipei City, Taiwan.
5
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.
6
Comprehensive Cancer Center, Taipei Medical University, Taipei, Taiwan. jywang2010@tmu.edu.tw.

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.

KEYWORDS:

Apoptosis; Ascorbate; Autophagy; Methamphetamine; Oxidative stress; Vitamin C

PMID:
26732595
DOI:
10.1007/s12035-015-9561-z
[Indexed for MEDLINE]

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