title: Differential protein profile of PC12 cells exposed to proteasomal inhibitor lactacystin.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and recent studies implicate a central role for ubiquitin-proteasome system (UPS) impairment in the etiopathogenesis of PD. To explore the possible role of UPS dysfunction in PD and the proteins involved, PC12 cells were treated with 10μM lactacystin, a 20S proteasome inhibitor, for 24h. Lactacystin induced cell death and α-synuclein-positive inclusions in cytoplasm. Following two-dimensional difference in-gel electrophoresis (2-D DIGE) which was used to separate the cellular proteins, the proteins that were significantly altered were analyzed and identified. Proteomic study identified 6 differentially expressed proteins between lactacystin-treated and control cells in this study. Four proteins (heat shock 70kDa protein 8, 78kDa glucose-regulated protein, serine proteinase inhibitor clade B member 6 and aldehyde reductase) were increased and 2 proteins (peripherin and tyrosine hydroxylase) were decreased following proteasomal inhibition. The results revealed that PC12 cells treated with 10μM lactacystin for 24h could be used as a cellular model of PD. The proteins identified in the present indicate not only the damage of proteasomal inhibition to the cells but also the possible responses of the cells. These data show that proteomic study may provide information relevant to biological basis for PD and potential new treatment targets.
authors.affiliation: Department of Neurology, The First Hospital, Jilin University, Changchun 130021, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Rehabilitation, The Second Hospital, Jilin University, Changchun 130041, China.
authors.forename: Haina
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Hospital, Jilin University, Changchun 130041, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Hospital, Jilin University, Changchun 130041, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Medicine, Norman Bethune Health Science Center, Jilin University, Changchun 130021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Neurology, The Second Hospital, Jilin University, Changchun 130041, China.
authors.forename: Qiuhui
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Hospital, Jilin University, Changchun 130021, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, The Second Hospital, Jilin University, Changchun 130041, China. Electronic address: zhang_lei@jlu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016923:Cell Death; D003593:Cytoplasm / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D002479:Inclusion Bodies / Q000378:metabolism; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000111:Acetylcysteine; D006360:Heat-Shock Proteins; D061988:Proteasome Inhibitors; D020543:Proteome; D014446:Tyrosine 3-Monooxygenase; D051844:alpha-Synuclein; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C067713:lactacystin
keywords: PC12; Parkinson's disease; Proteomics; Two-dimensional difference gel electrophoresis; Ubiquitin–proteasome system