Dataset Information
Downregulation of DEC1 contributes to the neurotoxicity induced by MPP+ by suppressing PI3K/Akt/GSK3? pathway.
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ABSTRACT: Aim
Differentiated embryonic chondrocyte gene 1 (DEC1) is involved in the neuronal differentiation and development. The aim of this study is to investigate the role of DEC1 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP+ )-induced PD model.Methods
The location of DEC1 and tyrosine hydroxylase (TH)-positive neurons were detected by immunofluorescence. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse subacute model of PD was established to evaluate the change of DEC1 expression in midbrain. Then, SH-SY5Y cells were used to investigate the role of DEC1 in MPP+ -induced neurotoxicity.Results
We showed that the co-expressed DEC1 and TH neurons took up more than 80% of the expressed TH neurons in the midbrain of mice. DEC1/TH double-positive neurons decreased by 40.6% in SNpc and 28.8% in VTA of MPTP-injured mice. Consistently, DEC1, TH and dopamine transporter (DAT) expression decreased in the midbrain of MPTP mice. In SY-SY5Y cells, MPP+ significantly suppressed DEC1 expression and increased the cleaved caspase 3/caspase 3 and Bax/Bcl-2. DEC1 overexpression relieved, whereas DEC1 knockdown aggravated MPP+ -induced cytotoxicity. Likewise, DEC1 overexpression and knockdown inversely regulated the expression of ?-catenin and PI3Kp110? (PIK3CA), an essential role in Wnt/?-catenin and PI3K/Akt signaling pathways. Interestingly, LY294002, an inhibitor of PI3K/Akt signaling, aggravated, whereas LiCl, an activator of Wnt/?-catenin signaling, abolished the reduction in DEC1 by MPP+ . It is established that these two pathways are interconnected by the phosphorylation status of GSK3?. DEC1 overexpression increased but MPP+ and DEC1 knockdown decreased GSK3? phosphorylation.Conclusion
Downregulation of DEC1 contributes to MPP+ -induced neurotoxicity by suppressing PI3K/Akt/GSK3? pathway.
SUBMITTER: Zhu Z
PROVIDER: S-EPMC6492752 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
Downregulation of DEC1 contributes to the neurotoxicity induced by MPP<sup>+</sup> by suppressing PI3K/Akt/GSK3β pathway.
CNS neuroscience & therapeutics 20170721 9
<h4>Aim</h4>Differentiated embryonic chondrocyte gene 1 (DEC1) is involved in the neuronal differentiation and development. The aim of this study is to investigate the role of DEC1 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP<sup>+</sup> )-induced PD model.<h4>Methods</h4>The location of DEC1 and tyrosine hydroxylase (TH)-positive neurons were detected by immunofluorescence. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse subacute model of PD was established to evaluate ...[more]