title: Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress.
abstract: Parkinson's disease (PD) is a neurodegenerative disease. Nicotine has been reported to have the role in preventing Parkinson's disease. However, its mechanism is still unclear. In present study we found that nicotine suppressed 1-methyl-4-phenylpyridinium ion(MPP+) toxicity in PC12 cells by MTT assay. The expression of thioredoxin-1(Trx-1) was decreased by MPP+, which was restored by nicotine. The nicotine suppressed expressions of Glucose-regulated protein 78(GRP78/Bip) and C/EBP homologous protein (CHOP) induced by MPP+. The methyllycaconitine (MLA), the inhibitor of α7nAChR and LY294002, the inhibitor of phosphatidylinositol 3-kinase (PI3K) blocked the suppressions of above molecules, respectively. Consistently, pretreatment with nicotine ameliorated the motor ability, restored the declines of Trx-1 and tyrosine hydroxylase (TH), and suppressed the expressions of Bip and CHOP induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Our results suggest that nicotine plays role in resisting MPP+/MPTP neurotoxicity through activating the α7nAChR/PI3K/Trx-1 pathway and suppressing ER stress.
authors.affiliation: Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China.
authors.forename: Yanxue
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China.
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.affiliation: Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Tobacco Chemistry of Yunnan Province, R&D Center of China Tobacco Yunnan Industrial Co., Ltd, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yao
authors.affiliation: Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China. Electronic address: jiebai662001@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D020267:MPTP Poisoning / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D016716:PC12 Cells / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013879:Thioredoxins / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000091342:Endoplasmic Reticulum Chaperone BiP; D009538:Nicotine; D018722:Nicotinic Agonists; D019869:Phosphatidylinositol 3-Kinases; D013879:Thioredoxins; D051742:Transcription Factor CHOP; D064569:alpha7 Nicotinic Acetylcholine Receptor; C497250:Ddit3 protein, mouse; C000717248:Hspa5 protein, mouse
keywords: MPP+/MPTP; Nicotine; Parkinson’s disease; Thioredoxin-1