title: Methylmercury induces the expression of TNF-α selectively in the brain of mice.
abstract: Methylmercury selectively damages the central nervous system (CNS). The tumor necrosis factor (TNF) superfamily includes representative cytokines that participate in the inflammatory response as well as cell survival, and apoptosis. In this study, we found that administration of methylmercury selectively induced TNF-α expression in the brain of mice. Although the accumulated mercury concentration in the liver and kidneys was greater than in the brain, TNF-α expression was induced to a greater extent in brain. Thus, it is possible that there may exist a selective mechanism by which methylmercury induces TNF-α expression in the brain. We also found that TNF-α expression was induced by methylmercury in C17.2 cells (mouse neural stem cells) and NF-κB may participate as a transcription factor in that induction. Further, we showed that the addition of TNF-α antagonist (WP9QY) reduced the toxicity of methylmercury to C17.2 cells. In contrast, the addition of recombinant TNF-α to the culture medium decreased the cell viability. We suggest that TNF-α may play a part in the selective damage of the CNS by methylmercury. Furthermore, our results indicate that the higher TNF-α expression induced by methylmercury maybe the cause of cell death, as TNF-α binds to its receptor after being released extracellularly.
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.|Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Onogawa16-2, Tsukuba, Ibaraki 305-8506, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Iwai-Shimada
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.|School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0232, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.|Department of Inhalation Toxicology Research, Korea Institute of Toxicology, Jeonbuk 56212, Republic of Korea.
authors.forename: Min-Seok
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Basic Medical Science, National Institute for Minamata Disease, Kumamoto 867-0008, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Fujimura
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Hitoyasu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Toyama
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Naganuma
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Gi-Wook
authors.initials: GW
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D010456:Peptides, Cyclic / Q000494:pharmacology; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology
chemical_list: D000931:Antidotes; D008767:Methylmercury Compounds; D016328:NF-kappa B; D010456:Peptides, Cyclic; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C501648:WP9QY peptide