@article{oai:nagoya.repo.nii.ac.jp:00024930,
 author = {Kumasaka, Mayuko Y. and Yajima, Ichiro and Ohgami, Nobutaka and Ninomiya, Hiromasa and Iida, Machiko and Li, Xiang and Oshino, Reina and Tanihata, Hiroko and Yoshinaga, Masafumi and Kato, Masashi},
 issue = {4},
 journal = {Neurotoxicity Research},
 month = {Nov},
 note = {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.},
 pages = {661--670},
 title = {Manganese-mediated decrease in levels of c-RET and tyrosine hydroxylase expression in vitro},
 volume = {32},
 year = {2017}
}