title: Protection against neurotoxicity by an autophagic mechanism.
abstract: The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson's disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.
authors.affiliation: Department of Neurology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, China.
authors.forename: Kangyong
authors.initials: K
authors.lastname: Liu
authors.forename: Jiankang
authors.initials: J
authors.lastname: Huang
authors.forename: Rongfu
authors.initials: R
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Liwei
authors.initials: L
authors.lastname: Shen
authors.forename: Jiajun
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Sun
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D000077102:Apium / Q000737:chemistry; D001343:Autophagy / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D012639:Seeds / Q000737:chemistry
chemical_list: D001572:Benzofurans; D018696:Neuroprotective Agents; C027125:3-n-butylphthalide; D015655:1-Methyl-4-phenylpyridinium