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Selenoprotein T Positively Regulates α‐synuclein Expression and Cell Proliferation in SK‐N‐SH Cells
Author(s) -
Zhu JianHong,
Zhu Hui,
Shao ZiQiang,
Sun ShengNan,
Zhang Xiong
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.802.16
Subject(s) - gene knockdown , substantia nigra , cell growth , microbiology and biotechnology , messenger rna , biology , chemistry , endocrinology , biochemistry , gene , dopamine , dopaminergic
The exclusive retention of selenium (Se) in brain during Se deficiency implicates an important role of this element in brain function and relevant disorders such as Parkinson's disease (PD). While the biological function of Se is mostly through selenoproteins, we have previously screened selenotranscriptome in five brain regions in a chronic mouse model of PD and identified some unique changes of selenoproteins. Amongst includes the expression of selenoprotein T (SelenoT) reduced in the substantia nigra, but increased in the cortex and pons of PD mice. In this study, we aimed to further understand the role of SelenoT in PD and the underlying mechanisms. Analysis in peripheral blood mononuclear cells showed an elevated level of SelenoT mRNA in PD patients compared with the controls. By using MPP + ‐treated SK‐N‐SH neuronal cells as a PD cellular model, we found that MPP + treatment increased SelenoT mRNA and protein expression. Results from siRNA knockdown and overexpression showed that SelenoT positively regulated cell proliferation and the mRNA and protein expression of α‐synuclein, a key molecule involved in PD pathogenesis. Knockdown of SelenoT led to elevated cellular Ca 2+ level, but reduced levels of p53 and reactive oxygen species, which may involve in the regulation of SelenoT on α‐synuclein expression. Results from siRNA knockdown also showed a reduction in cyclin‐dependent kinase 4 (CDK4), but an increased activity in CDK2, p‐38 and p‐JNK1/2, which is implicated the regulation of cell proliferation. Taken together, our data suggest SelenoT is responsive to PD inducer and may play a role in the pathogenesis of PD. Further work are needed to clarify the specific targets of SelenoT, as well as its role in PD by using conditional knockout animal models.