Knockdown of TXNIP attenuates methylmercury toxicity in mouse neuronal C17.2 cells
Methylmercury is an environmental pollutant that causes severe central nervous system damage. However, the mechanism involved in its toxicity remains unclear. In this study, expression of thioredoxin-interacting protein (TXNIP), which is involved in the regulation of intracellular redox status, was...
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| Published in | Fundamental Toxicological Sciences Vol. 12; no. 2; pp. 29 - 32 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
The Japanese Society of Toxicology
2025
一般社団法人 日本毒性学会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2189-115X 2189-115X |
| DOI | 10.2131/fts.12.29 |
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| Abstract | Methylmercury is an environmental pollutant that causes severe central nervous system damage. However, the mechanism involved in its toxicity remains unclear. In this study, expression of thioredoxin-interacting protein (TXNIP), which is involved in the regulation of intracellular redox status, was rapidly induced in mouse neuronal C17.2 cells in response to methylmercury exposure. In addition, C17.2 cells transfected with small interfering RNA against TXNIP mRNA showed greater resistance to methylmercury than control cells. These findings suggest that TXNIP is a novel factor involved in enhancing methylmercury toxicity and that methylmercury may cause cell death by inducing TXNIP expression. |
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| AbstractList | Methylmercury is an environmental pollutant that causes severe central nervous system damage. However, the mechanism involved in its toxicity remains unclear. In this study, expression of thioredoxin-interacting protein (TXNIP), which is involved in the regulation of intracellular redox status, was rapidly induced in mouse neuronal C17.2 cells in response to methylmercury exposure. In addition, C17.2 cells transfected with small interfering RNA against TXNIP mRNA showed greater resistance to methylmercury than control cells. These findings suggest that TXNIP is a novel factor involved in enhancing methylmercury toxicity and that methylmercury may cause cell death by inducing TXNIP expression. |
| Author | Fukushima, Ryoko Yadoya, Soujun Hwang, Gi-Wook Yamashita, Naoya Yamagata, Ryota |
| Author_xml | – sequence: 1 fullname: Hwang, Gi-Wook organization: Division of Environmental and Health Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University – sequence: 1 fullname: Yadoya, Soujun organization: Division of Environmental and Health Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University – sequence: 1 fullname: Fukushima, Ryoko organization: Division of Environmental and Health Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University – sequence: 1 fullname: Yamashita, Naoya organization: Division of Environmental and Health Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University – sequence: 1 fullname: Yamagata, Ryota organization: Division of Environmental and Health Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University |
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| Cites_doi | 10.2131/fts.9.159 10.3390/ijms25073886 10.1155/2022/8645714 10.1089/ars.2021.0038 10.3390/ijms21249357 10.1016/j.lfs.2020.118031 10.3389/fnmol.2023.1210962 10.1007/s43188-024-00277-6 10.1620/tjem.242.1 10.1177/019262339702500612 10.1007/s43188-021-00087-0 |
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| References | Tsubaki, H., Tooyama, I. and Walker, D.G. (2020): Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases. Int. J. Mol. Sci., 21, 1-24. Toyama, T., Wang, Y., Kim, M.S., Takahashi, T., Naganuma, A. and Hwang, G.W. (2021): Increased expression of TCF3, transcription factor 3, is a defense response against methylmercury toxicity in mouse neuronal C17.2 cells. Toxicol. Res., 37, 451-458. Sato, M., Toyama, T., Kim, M.S., Lee, J.Y., Hoshi, T., Miura, N., Naganuma, A. and Hwang, G.W. (2020): Increased putrescine levels due to ODC1 overexpression prevents mitochondrial dysfunction-related apoptosis induced by methylmercury. Life Sci., 256, 118031. Yamashita, N., Yokoyama, Y., Kumagai, A., Fukushima, R., Yamagata, R. and Hwang, G.W. (2025): SRXN1 is a novel protective factor against methylmercury-induced apoptosis in C17.2 mouse neural stem cells. Toxicol. Res., 41, 167-173. Zhang, Y., Xing, C.J., Liu, X., Li, Y.H., Jia, J., Feng, J.G., Yang, C.J., Chen, Y. and Zhou, J. (2022): Thioredoxin-Interacting Protein (TXNIP) Knockdown Protects against Sepsis-Induced Brain Injury and Cognitive Decline in Mice by Suppressing Oxidative Stress and Neuroinflammation. Oxid. Med. Cell. Longev., 2022, 8645714. Eto, K. (1997): Pathology of Minamata disease. Toxicol. Pathol., 25, 614-623. García-Hernández, B. and Morán, J. (2023): Txnip expression promotes JNK-mediated neuronal death in response to reactive oxygen species. Front. Mol. Neurosci., 16, 1210962. Masutani, H. (2022): Thioredoxin-Interacting Protein in Cancer and Diabetes. Antioxid. Redox Signal., 36, 1001-1022. Yamashita, N., Uchiyama, M., Yamagata, R. and Hwang, G.W. (2024): Methylmercury induces apoptosis in mouse C17.2 neural stem cells through the induction of OSGIN1 expression by NRF2. Int. J. Mol. Sci., 25, 3886. Lee, J.Y., Kim, J.M., Noguchi, T., Matsuzawa, A., Naganuma, A. and Hwang, G.W. (2022): Deubiquitinase USP54 attenuates methylmercury toxicity in human embryonic kidney 293 cells. Fundam. Toxicol. Sci., 9, 159-162. Tatsuta, N., Murata, K., Iwai-Shimada, M., Yaginuma-Sakurai, K., Satoh, H. and Nakai, K. (2017): Psychomotor Ability in Children Prenatally Exposed to Methylmercury: The 18-Month Follow-Up of Tohoku Study of Child Development. Tohoku J. Exp. Med., 242, 1-8. 11 1 2 3 4 5 6 7 8 9 10 |
| References_xml | – reference: Lee, J.Y., Kim, J.M., Noguchi, T., Matsuzawa, A., Naganuma, A. and Hwang, G.W. (2022): Deubiquitinase USP54 attenuates methylmercury toxicity in human embryonic kidney 293 cells. Fundam. Toxicol. Sci., 9, 159-162. – reference: Eto, K. (1997): Pathology of Minamata disease. Toxicol. Pathol., 25, 614-623. – reference: García-Hernández, B. and Morán, J. (2023): Txnip expression promotes JNK-mediated neuronal death in response to reactive oxygen species. Front. Mol. Neurosci., 16, 1210962. – reference: Tatsuta, N., Murata, K., Iwai-Shimada, M., Yaginuma-Sakurai, K., Satoh, H. and Nakai, K. (2017): Psychomotor Ability in Children Prenatally Exposed to Methylmercury: The 18-Month Follow-Up of Tohoku Study of Child Development. Tohoku J. Exp. Med., 242, 1-8. – reference: Tsubaki, H., Tooyama, I. and Walker, D.G. (2020): Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases. Int. J. Mol. Sci., 21, 1-24. – reference: Yamashita, N., Uchiyama, M., Yamagata, R. and Hwang, G.W. (2024): Methylmercury induces apoptosis in mouse C17.2 neural stem cells through the induction of OSGIN1 expression by NRF2. Int. J. Mol. Sci., 25, 3886. – reference: Zhang, Y., Xing, C.J., Liu, X., Li, Y.H., Jia, J., Feng, J.G., Yang, C.J., Chen, Y. and Zhou, J. (2022): Thioredoxin-Interacting Protein (TXNIP) Knockdown Protects against Sepsis-Induced Brain Injury and Cognitive Decline in Mice by Suppressing Oxidative Stress and Neuroinflammation. Oxid. Med. Cell. Longev., 2022, 8645714. – reference: Masutani, H. (2022): Thioredoxin-Interacting Protein in Cancer and Diabetes. Antioxid. Redox Signal., 36, 1001-1022. – reference: Toyama, T., Wang, Y., Kim, M.S., Takahashi, T., Naganuma, A. and Hwang, G.W. (2021): Increased expression of TCF3, transcription factor 3, is a defense response against methylmercury toxicity in mouse neuronal C17.2 cells. Toxicol. Res., 37, 451-458. – reference: Yamashita, N., Yokoyama, Y., Kumagai, A., Fukushima, R., Yamagata, R. and Hwang, G.W. (2025): SRXN1 is a novel protective factor against methylmercury-induced apoptosis in C17.2 mouse neural stem cells. Toxicol. Res., 41, 167-173. – reference: Sato, M., Toyama, T., Kim, M.S., Lee, J.Y., Hoshi, T., Miura, N., Naganuma, A. and Hwang, G.W. (2020): Increased putrescine levels due to ODC1 overexpression prevents mitochondrial dysfunction-related apoptosis induced by methylmercury. Life Sci., 256, 118031. – ident: 3 doi: 10.2131/fts.9.159 – ident: 9 doi: 10.3390/ijms25073886 – ident: 11 doi: 10.1155/2022/8645714 – ident: 4 doi: 10.1089/ars.2021.0038 – ident: 8 doi: 10.3390/ijms21249357 – ident: 5 doi: 10.1016/j.lfs.2020.118031 – ident: 2 doi: 10.3389/fnmol.2023.1210962 – ident: 10 doi: 10.1007/s43188-024-00277-6 – ident: 6 doi: 10.1620/tjem.242.1 – ident: 1 doi: 10.1177/019262339702500612 – ident: 7 doi: 10.1007/s43188-021-00087-0 |
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| Title | Knockdown of TXNIP attenuates methylmercury toxicity in mouse neuronal C17.2 cells |
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