論文

査読有り
2017年11月

Manganese-Mediated Decrease in Levels of c-RET and Tyrosine Hydroxylase Expression In Vitro

NEUROTOXICITY RESEARCH
  • Mayuko Y. Kumasaka
  • ,
  • Ichiro Yajima
  • ,
  • Nobutaka Ohgami
  • ,
  • Hiromasa Ninomiya
  • ,
  • Machiko Iida
  • ,
  • Xiang Li
  • ,
  • Reina Oshino
  • ,
  • Hiroko Tanihata
  • ,
  • Masafumi Yoshinaga
  • ,
  • Masashi Kato

32
4
開始ページ
661
終了ページ
670
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s12640-017-9783-0
出版者・発行元
SPRINGER

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 mu M 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 mu M) 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.

Web of Science ® 被引用回数 : 4

リンク情報
DOI
https://doi.org/10.1007/s12640-017-9783-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28730349
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000410949900013&DestApp=WOS_CPL

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