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Activation of ornithine decarboxylase protects against methylmercury toxicity by increasing putrescine

Authors :
Nobuhiko Miura
Akira Naganuma
Takashi Toyama
Jin-Yong Lee
Gi Wook Hwang
Masayuki Sato
Source :
Toxicology and applied pharmacology. 356
Publication Year :
2018

Abstract

We previously reported significantly increased level of putrescine, a polyamine, in the brains of mice administered methylmercury. Moreover, addition of putrescine to culture medium reduced methylmercury toxicity in C17.2 mouse neural stem cells. In this study, the role of ornithine decarboxylase (ODC), an enzyme involved in putrescine synthesis, in response to methylmercury toxicity was investigated. Methylmercury increased ODC activity in mouse cerebrum and cerebellum, but this increase was hardly observed in the kidney and liver, where methylmercury accumulated at a high concentration. In the cerebrum and cerebellum, increased putrescine was observed with methylmercury administration. Methylmercury increased ODC activity in C17.2 cells, but this was almost completely abolished in the presence of an ODC inhibitor. Methylmercury also increased the level of ODC protein in mouse brain and C17.2 cells. In addition, C17.2 cells pretreated with ODC inhibitor showed higher methylmercury sensitivity than control cells. These results suggest that the increased ODC activity by methylmercury is involved in the increase in putrescine level, and ODC plays an important role in the reduction of methylmercury toxicity. This is the first study to provide evidence that increased ODC activity may be a protective response against methylmercury-induced neurotoxicity.

Details

ISSN :
10960333
Volume :
356
Database :
OpenAIRE
Journal :
Toxicology and applied pharmacology
Accession number :
edsair.doi.dedup.....289dc890e20e4e1f83d115068a41bfea