2024-03-28T10:25:31Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00024930
2023-01-16T04:14:03Z
499:500:501
Manganese-mediated decrease in levels of c-RET and tyrosine hydroxylase expression in vitro
Kumasaka, Mayuko Y.
74266
Yajima, Ichiro
74267
Ohgami, Nobutaka
74268
Ninomiya, Hiromasa
74269
Iida, Machiko
74270
Li, Xiang
74271
Oshino, Reina
74272
Tanihata, Hiroko
74273
Yoshinaga, Masafumi
74274
Kato, Masashi
74275
Manganese
Metals
Protein expression
RET
Tyrosine kinase
Previous studies showed that overexposure to manganese causes parkinsonism, a disorder of dopaminergic neurons. Previous studies also showed that activity of c-RET kinase controls dopamine production through regulation of tyrosine hydroxylase (TH) expression, suggesting the involvement of c-RET in the development of parkinsonism. To our knowledge, however, there is no report showing a correlation between manganese-mediated parkinsonism and c-RET. In this study, we examined the effect of manganese on the expression and/or activation levels of c-RET and TH in human TH-expressing cells (TGW cells). We first found that treatment with 30 and 100 μM manganese resulted in reduction of c-RET transcript level and degradation of c-RET protein through promotion of ubiquitination. We then examined the biological significance of manganese-mediated decrease of c-RET protein expression. Decreased TH expression with decreased c-RET kinase activity was observed in c-RET protein-depleted TGW cells by treatment with manganese (30 μM) as well as by c-RET siRNA transfection. Since TH protein has been shown to be involved in the dopamine-producing pathway in previous studies, our results indicate the possibility that manganese-mediated reduction of TH expression and phosphorylation via decreased expression of c-RET protein in neural cells is involved in parkinsonism induced by manganese.
journal article
Springer
2017-11
application/pdf
Neurotoxicity Research
4
32
661
670
http://doi.org/10.1007/s12640-017-9783-0
http://hdl.handle.net/2237/27152
1029-8428
https://nagoya.repo.nii.ac.jp/record/24930/files/Kumasaka_et_al.pdf
eng
https://doi.org/10.1007/s12640-017-9783-0
The final publication is available at Springer via http://doi.org/10.1007/s12640-017-9783-0