title: Identification of chaperones in a MPP+-induced and ATRA/TPA-differentiated SH-SY5Y cell PD model.
abstract: Parkinson's disease (PD) is characterized by the pathological accumulation of misfolded proteins. Molecular chaperones assist in the proper folding of proteins and removal of irreversibly misfolded proteins. This study aims to identify potential chaperones associated with protein misfolding and accumulation in PD. ATRA/TPA-differentiated SH-SY5Y cells were treated with 1 mM of MPP+for 48 hours. Proteins were analyzed by 2D-DIGE followed by MALDI-ToF MS. The treatment of differentiated SH-SY5Y cells by MPP+led to the unambiguous identification of 10 protein spots, which corresponds to six proteins. Among these six proteins, four were chaperone proteins including nucleophosmin (NPM1), chaperonin-containing TCP-1 subunit 2 (CCT2 or CCTβ), heat shock 90 kDa protein 1 beta (HSP90AB1 or HSP90-β), and tyrosin3/tryptopha5-monoxygenase activation protein, zeta polypeptide (14-3-3ζ, gene symbol: Ywhaz). To our knowledge, this is the first report that linked the upregulation of chaperones after MPP+treatment with SH-SY5Y cells. However, the NPM1 protein was identified for the first time in the PD model. The upregulation of four chaperone proteins provided evidence that these chaperones have a complementary effect on protein misfolding in the pathogenesis of PD, and hold promise as a good therapeutic target for PD treatment.
authors.affiliation: Department of Neurology, Shanghai East Hospital, Tongji University Shanghai 200120, P. R. China.
authors.forename: Hongrong
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Neurology, Shanghai East Hospital, Tongji University Shanghai 200120, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Neurology, The First Hospital of Jilin University Shanghai 130021, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chang
authors.affiliation: Department of Neurology, Shanghai East Hospital, Tongji University Shanghai 200120, P. R. China.
authors.forename: Dongya
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Neurology, Shanghai East Hospital, Tongji University Shanghai 200120, P. R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Neurology, Shanghai East Hospital, Tongji University Shanghai 200120, P. R. China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Neurology, Shanghai East Hospital, Tongji University Shanghai 200120, P. R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Xiong
authors.affiliation: Department of Neurology, The First Hospital of Jilin University Shanghai 130021, P. R. China.
authors.forename: Linsen
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Neurology, Shanghai East Hospital, Tongji University Shanghai 200120, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
keywords: Chaperone proteins; MPP+; SH-SY5Y cells; proteomic analysis