title: Celastrol protects human neuroblastoma SH-SY5Y cells from rotenone-induced injury through induction of autophagy.
abstract: Celastrol, an active component found in the Chinese herb tripterygium wilfordii has been identified as a neuroprotective agent for neurodegenerative diseases including Parkinson's disease (PD) through unknown mechanism. Celastrol can induce autophagy, which plays a neuroprotective role in PD. We tested the protective effect of celastrol on rotenone-induced injury and investigated the underlying mechanism using human neuroblastoma SH-SY5Y cells. The SH-SY5Y cells were treated with celastrol before rotenone exposure. The cells survival, apoptosis, accumulation of α-synuclein, oxidative stress and mitochondrial function, and autophagy production were analyzed. We found celastrol (500 nM) pre-treatment enhanced cell viability (by 28.99%, P<0.001), decreased cell apoptosis (by 54.38%, P<0.001), increased SOD and GSH (by 120.53% and 90.46%, P<0.01), reduced accumulation of α-synuclein (by 35.93%, P<0.001) and ROS generation (by 33.99%, P<0.001), preserved MMP (33.93±3.62%, vs. 15.10±0.71% of JC-1 monomer, P<0.001) and reduced the level of cytochrome C in cytosol (by 45.57%, P<0.001) in rotenone treated SH-SY5Y cells. Moreover, celastrol increased LC3-II/LC3 I ratio by 60.92% (P<0.001), indicating that celastrol activated autophagic pathways. Inhibiting autophagy by 3-methyladenine (3-MA) abolished the protective effects of celastrol. Our results suggested that celastrol protects SH-SY5Y cells from rotenone induced injuries and autophagic pathway is involved in celastrol neuroprotective effects.
authors.affiliation: Department of Neurology, First affiliated hospital, Medical College of Xi'an Jiao Tong University, Xi'an 710061, China.
authors.forename: Yong-Ning
authors.initials: YN
authors.lastname: Deng
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Qiu-Min
authors.initials: QM
authors.lastname: Qu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D009447:Neuroblastoma / Q000276:immunology / Q000473:pathology*; D053978:Pentacyclic Triterpenes; D012402:Rotenone / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D012402:Rotenone; C050414:celastrol