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Activation of ornithine decarboxylase protects against methylmercury toxicity by increasing putrescine
- 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Cerebellum
genetic structures
Enzyme Activators
Toxicology
Ornithine Decarboxylase
Ornithine decarboxylase
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Mice
Neural Stem Cells
Internal medicine
medicine
Putrescine
Animals
Tissue Distribution
Enzyme Inhibitors
Methylmercury
Pharmacology
chemistry.chemical_classification
fungi
Neurotoxicity
Brain
Mercury
Methylmercury Compounds
Ornithine Decarboxylase Inhibitors
medicine.disease
Enzyme Activation
030104 developmental biology
Endocrinology
Enzyme
medicine.anatomical_structure
chemistry
Liver
Toxicity
Mercury Poisoning
Polyamine
Subjects
Details
- ISSN :
- 10960333
- Volume :
- 356
- Database :
- OpenAIRE
- Journal :
- Toxicology and applied pharmacology
- Accession number :
- edsair.doi.dedup.....289dc890e20e4e1f83d115068a41bfea