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Protective effect of gastrodin against methamphetamine-induced autophagy in human dopaminergic neuroblastoma SH-SY5Y cells via the AKT/mTOR signaling pathway.
Neurosci Lett. 2019 08 10; 707:134287.NL

Abstract

Methamphetamine (METH) has been shown to induce neuropathological dysfunction and irreversible brain cell damage. Prior studies indicated the involvement of autophagy in METH-induced neurotoxicity. However, the underlying mechanism by which autophagy contributes to METH-induced neurotoxicity remains elusive. Gastrodin, a primary bioactive constituent of Gastrodia elata-an orchid used in traditional Chinese medicine-is used widely to treat stroke, dementia, and headache. This study investigates whether METH induces autophagy in the human dopaminergic neuroblastoma cell line SH-SY5Y, then examines the neuroprotective effects of gastrodin against autophagy in METH-treated SH-SY5Y cells. The effects of METH on the protein expressions of autophagy-related genes (LC3B and Beclin-1) were evaluated with and without gastrodin. The presence of autophagosomes in the METH-induced treatment with and without gastrodin is revealed through transmission electron microscopy. Pharmacological intervention was employed to study the role of the AKT/mTOR signaling pathway in the gastrodin-mediated neuroprotection against METH-induced autophagy. The present results indicate that METH exposure elevates the protein expression levels of LC3B and Beclin-1 in a dose- and time-dependent manner. Gastrodin is observed to block the METH-induced upregulation of LC3B and Beclin-1 protein expression significantly. Gastrodin is found to exhibit an anti-autophagic effect on the inhibition of the METH-induced Beclin-1 protein expression, partly via the AKT/mTOR These findings may aid the development of a gastrodin-based therapeutic strategy for treating METH-induced neurotoxicity.

Authors+Show Affiliations

School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, China.School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, China.School of Basic Medicine, Kunming Medical University, Kunming, Yunnan Province, China.School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China; CUHK-SDU Joint Laboratory of Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, China.School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, China.School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, China.School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, China.School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, China. Electronic address: lilihua1229@sohu.com.School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, China. Electronic address: lizhenlaura@126.com.

Pub Type(s)

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

Language

eng

PubMed ID

31128157

Citation

Yang, Genmeng, et al. "Protective Effect of Gastrodin Against Methamphetamine-induced Autophagy in Human Dopaminergic Neuroblastoma SH-SY5Y Cells Via the AKT/mTOR Signaling Pathway." Neuroscience Letters, vol. 707, 2019, p. 134287.
Yang G, Zeng X, Li J, et al. Protective effect of gastrodin against methamphetamine-induced autophagy in human dopaminergic neuroblastoma SH-SY5Y cells via the AKT/mTOR signaling pathway. Neurosci Lett. 2019;707:134287.
Yang, G., Zeng, X., Li, J., Leung, C. K., Zhang, D., Hong, S., He, Y., Huang, J., Li, L., & Li, Z. (2019). Protective effect of gastrodin against methamphetamine-induced autophagy in human dopaminergic neuroblastoma SH-SY5Y cells via the AKT/mTOR signaling pathway. Neuroscience Letters, 707, 134287. https://doi.org/10.1016/j.neulet.2019.134287
Yang G, et al. Protective Effect of Gastrodin Against Methamphetamine-induced Autophagy in Human Dopaminergic Neuroblastoma SH-SY5Y Cells Via the AKT/mTOR Signaling Pathway. Neurosci Lett. 2019 08 10;707:134287. PubMed PMID: 31128157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effect of gastrodin against methamphetamine-induced autophagy in human dopaminergic neuroblastoma SH-SY5Y cells via the AKT/mTOR signaling pathway. AU - Yang,Genmeng, AU - Zeng,Xiaofeng, AU - Li,Juan, AU - Leung,Chi-Kwan, AU - Zhang,Dongxian, AU - Hong,Shijun, AU - He,Yongwang, AU - Huang,Jian, AU - Li,Lihua, AU - Li,Zhen, Y1 - 2019/05/23/ PY - 2018/12/24/received PY - 2019/05/20/revised PY - 2019/05/21/accepted PY - 2019/5/28/pubmed PY - 2020/3/12/medline PY - 2019/5/26/entrez KW - AKT/mTOR KW - Autophagy KW - Gastrodin KW - METH KW - Methamphetamine KW - SH-SY5Y cells SP - 134287 EP - 134287 JF - Neuroscience letters JO - Neurosci Lett VL - 707 N2 - Methamphetamine (METH) has been shown to induce neuropathological dysfunction and irreversible brain cell damage. Prior studies indicated the involvement of autophagy in METH-induced neurotoxicity. However, the underlying mechanism by which autophagy contributes to METH-induced neurotoxicity remains elusive. Gastrodin, a primary bioactive constituent of Gastrodia elata-an orchid used in traditional Chinese medicine-is used widely to treat stroke, dementia, and headache. This study investigates whether METH induces autophagy in the human dopaminergic neuroblastoma cell line SH-SY5Y, then examines the neuroprotective effects of gastrodin against autophagy in METH-treated SH-SY5Y cells. The effects of METH on the protein expressions of autophagy-related genes (LC3B and Beclin-1) were evaluated with and without gastrodin. The presence of autophagosomes in the METH-induced treatment with and without gastrodin is revealed through transmission electron microscopy. Pharmacological intervention was employed to study the role of the AKT/mTOR signaling pathway in the gastrodin-mediated neuroprotection against METH-induced autophagy. The present results indicate that METH exposure elevates the protein expression levels of LC3B and Beclin-1 in a dose- and time-dependent manner. Gastrodin is observed to block the METH-induced upregulation of LC3B and Beclin-1 protein expression significantly. Gastrodin is found to exhibit an anti-autophagic effect on the inhibition of the METH-induced Beclin-1 protein expression, partly via the AKT/mTOR These findings may aid the development of a gastrodin-based therapeutic strategy for treating METH-induced neurotoxicity. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/31128157/Protective_effect_of_gastrodin_against_methamphetamine_induced_autophagy_in_human_dopaminergic_neuroblastoma_SH_SY5Y_cells_via_the_AKT/mTOR_signaling_pathway_ DB - PRIME DP - Unbound Medicine ER -