The role of FAM171A2-GRN-NF-κB pathway in TBBPA induced oxidative stress and inflammatory response in mouse-derived hippocampal neuronal HT22 cells
Tetrabromobisphenol A (TBBPA) is one of the brominated flame retardants (BFRs) widely used in industry, which has a broad toxic effect on organisms. However, there is still limited research on the neurotoxic mechanism of TBBPA. Using mouse hippocampal neurons (HT22) cells, the toxicity of TBBPA was...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| author | Yi Wang Jing Shan Ling Zhang Rui Wang Meng-Yu Wu Hong-Mei Li Hai-Ming Xu |
| author_facet | Yi Wang Jing Shan Ling Zhang Rui Wang Meng-Yu Wu Hong-Mei Li Hai-Ming Xu |
| author_sort | Yi Wang |
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| description | Tetrabromobisphenol A (TBBPA) is one of the brominated flame retardants (BFRs) widely used in industry, which has a broad toxic effect on organisms. However, there is still limited research on the neurotoxic mechanism of TBBPA. Using mouse hippocampal neurons (HT22) cells, the toxicity of TBBPA was evaluated, especially focusing on its alteration on the key molecules in FAM171A2-GRN-NF-κB signaling pathway. The results showed that TBBPA exposure could lead to an increase in the production of inflammation-related genes IL-6, iNOS, TGF-β1, COX2, and TNF-α in both HT22 cells and HT22-AD-model, intensifying the inflammatory response; it inhibits the mRNA expression of antioxidative enzymes genes Sod1, Cat, Gpx1, and Gsta1, resulting in reduced antioxidant enzyme activities of SOD, CAT, and GSH-Px/GPX. Mechanistically, TBBPA caused the upregulation of FAM171A2 expression level, alongside increased GRN, IκBα and p65 levels; whereas the expression of GRN, IκBα and p65 was decreased after FAM171A2 knockdown, demonstrating TBBPA-induced upregulation of FAM171A2 should be responsible for the increased GRN, IκBα and p65 expression. Therefore, for the first time, our data indicate that TBBPA-induced oxidative stress and inflammatory response is closely related to the FAM171A2-GRN-NF-κB pathway. |
| format | Article |
| id | doaj-art-18723c6d595746159e0045977a00cf7c |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-18723c6d595746159e0045977a00cf7c2025-01-23T05:25:34ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117445The role of FAM171A2-GRN-NF-κB pathway in TBBPA induced oxidative stress and inflammatory response in mouse-derived hippocampal neuronal HT22 cellsYi Wang0Jing Shan1Ling Zhang2Rui Wang3Meng-Yu Wu4Hong-Mei Li5Hai-Ming Xu6School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Department of Experimental Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaSchool of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Xi’an GEM Flowers Changqing Hospital, Xi’an, Shanxi 710000, ChinaSchool of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, ChinaSchool of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, ChinaSchool of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Xi’an GEM Flowers Changqing Hospital, Xi’an, Shanxi 710000, ChinaThe Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China; School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China; Corresponding author at: The Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China.School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Corresponding author at: School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China.Tetrabromobisphenol A (TBBPA) is one of the brominated flame retardants (BFRs) widely used in industry, which has a broad toxic effect on organisms. However, there is still limited research on the neurotoxic mechanism of TBBPA. Using mouse hippocampal neurons (HT22) cells, the toxicity of TBBPA was evaluated, especially focusing on its alteration on the key molecules in FAM171A2-GRN-NF-κB signaling pathway. The results showed that TBBPA exposure could lead to an increase in the production of inflammation-related genes IL-6, iNOS, TGF-β1, COX2, and TNF-α in both HT22 cells and HT22-AD-model, intensifying the inflammatory response; it inhibits the mRNA expression of antioxidative enzymes genes Sod1, Cat, Gpx1, and Gsta1, resulting in reduced antioxidant enzyme activities of SOD, CAT, and GSH-Px/GPX. Mechanistically, TBBPA caused the upregulation of FAM171A2 expression level, alongside increased GRN, IκBα and p65 levels; whereas the expression of GRN, IκBα and p65 was decreased after FAM171A2 knockdown, demonstrating TBBPA-induced upregulation of FAM171A2 should be responsible for the increased GRN, IκBα and p65 expression. Therefore, for the first time, our data indicate that TBBPA-induced oxidative stress and inflammatory response is closely related to the FAM171A2-GRN-NF-κB pathway.http://www.sciencedirect.com/science/article/pii/S0147651324015215Bisphenol compoundsNeurotoxicityOxidative stressInflammation responseMolecular mechanism |
| spellingShingle | Yi Wang Jing Shan Ling Zhang Rui Wang Meng-Yu Wu Hong-Mei Li Hai-Ming Xu The role of FAM171A2-GRN-NF-κB pathway in TBBPA induced oxidative stress and inflammatory response in mouse-derived hippocampal neuronal HT22 cells Ecotoxicology and Environmental Safety Bisphenol compounds Neurotoxicity Oxidative stress Inflammation response Molecular mechanism |
| title | The role of FAM171A2-GRN-NF-κB pathway in TBBPA induced oxidative stress and inflammatory response in mouse-derived hippocampal neuronal HT22 cells |
| title_full | The role of FAM171A2-GRN-NF-κB pathway in TBBPA induced oxidative stress and inflammatory response in mouse-derived hippocampal neuronal HT22 cells |
| title_fullStr | The role of FAM171A2-GRN-NF-κB pathway in TBBPA induced oxidative stress and inflammatory response in mouse-derived hippocampal neuronal HT22 cells |
| title_full_unstemmed | The role of FAM171A2-GRN-NF-κB pathway in TBBPA induced oxidative stress and inflammatory response in mouse-derived hippocampal neuronal HT22 cells |
| title_short | The role of FAM171A2-GRN-NF-κB pathway in TBBPA induced oxidative stress and inflammatory response in mouse-derived hippocampal neuronal HT22 cells |
| title_sort | role of fam171a2 grn nf κb pathway in tbbpa induced oxidative stress and inflammatory response in mouse derived hippocampal neuronal ht22 cells |
| topic | Bisphenol compounds Neurotoxicity Oxidative stress Inflammation response Molecular mechanism |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324015215 |
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