title: Induction of Dickkopf-1 contributes to the neurotoxicity of MPP+ in PC12 cells via inhibition of the canonical Wnt signaling pathway.
abstract: The secreted glycoprotein Dickkopf-1 (Dkk1), an antagonist of the Wnt/β-catenin pathway, has been implicated in many neurodegenerative diseases. However, it is unknown whether Dkk1 is involved in the pathogenesis of Parkinson's disease (PD). In this study, we discovered that Dkk1 was induced in MPP(+)-treated PC12 cells and the increase of Dkk1 preceded PC12 cell loss. RhDkk1 aggravated the neurotoxicity of MPP(+) in PC12 cells. Furthermore, the level of Dkk1 was correlated with the number of apoptotic PC12 cells. The apoptosis could be decreased by Dkk1-siRNA in MPP(+)-induced PC12 cells and Dkk1-siRNA regulated the expression of β-catenin and p-Ser9-GSK-3β in MPP(+)-induced PC12 cells. LiCl (an inhibitor of GSK-3β) also rescued the loss of PC12 cell viability and the apoptosis induced by MPP(+). These data suggest that the induction of Dkk1 contributes to the MPP(+)-induced neurotoxicity in PC12 cells via inhibition of the canonical Wnt pathway and Dkk1 antagonists which could rescue the Wnt pathway might be neuroprotective in PD.
authors.affiliation: Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan 430030, Hubei Province, China.
authors.forename: Yaoyan
authors.initials: Y
authors.lastname: Dun
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhengguo
authors.initials: Z
authors.lastname: Xiong
authors.forename: Mei
authors.initials: M
authors.lastname: Feng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Jizhou
authors.initials: J
authors.lastname: Xiang
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism; D051381:Rats; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000502:physiology*
chemical_list: C531384:Dkk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D015655:1-Methyl-4-phenylpyridinium