Activation of ornithine decarboxylase protects against methylmercury toxicity by increasing putrescine.
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.
['Sato|Masayuki|M|', 'Toyama|Takashi|T|', 'Lee|Jin-Yong|JY|', 'Miura|Nobuhiko|N|', 'Naganuma|Akira|A|', 'Hwang|Gi-Wook|GW|']
D000818:Animals D001921:Brain D002460:Cell Line D004789:Enzyme Activation D020536:Enzyme Activators D004791:Enzyme Inhibitors D008099:Liver D008628:Mercury D008630:Mercury Poisoning D008767:Methylmercury Compounds D051379:Mice D058953:Neural Stem Cells D009955:Ornithine Decarboxylase D065108:Ornithine Decarboxylase Inhibitors D011700:Putrescine D014018:Tissue Distribution
Ornithine Decarboxylase Methylmercury Putrescine