BIOLOGICAL TRACE ELEMENT RESEARCH
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2025
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IF 3.6
Liu Kan,Tao Tao,Li Ranhong,Wang Huanping,Wang Li,Wu Haiying
Arsenic exposure is well-established to cause neurotoxicity, but its underlying molecular mechanisms remain unclear. This study investigates the effects of early-life arsenic exposure on the nervous system of offspring. Female mice were exposed to NaAsO₂, and alterations in learning, memory, and hippocampal lesions in offspring were assessed. Transcriptome analysis, protein interaction studies, and cellular experiments were integrated to identify key regulatory factors in arsenic-induced neurotoxicity. Arsenic interacts with HUWE1, significantly downregulating its protein expression. HUWE1 inhibition enhances GPX8 stability by reducing its ubiquitination. GPX8 disrupts histone epigenetic modifications by promoting GSH synthesis and arsenic methylation, leading to elevated H3K9 levels. HUWE1 also interacts with KDM3A, and its inhibition reduces KDM3A-mediated H3K9me1/me2 demethylation, amplifying H3K9me2-mediated transcriptional repression of LARS2 and triggering PANoptosis. This study provides novel molecular insights into arsenic-induced neurotoxicity and highlights potential therapeutic targets to mitigate arsenic-related nervous system damage.
研究领域:
毒理学
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神经生物学
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表观遗传学
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分子毒理学
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发育神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
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2024
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IF 7.7
Jianjun Chen,Yinyin Wei,Jiameng Zhou,Xianglin Cao,Rongjie Yuan,Yaoyajie Lu,Yi Guo,Xue Shao,Weidi Sun,Mengtao Jia,Xiuli Chen
Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 μg/L, 1 μg/L, and 2 μg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development. Expression of cardiac development-related genes ( vmhc , myh6 , nkx2.5 , tbx5a , gata4 , tbx2b , nppa ) is dysregulated. Transgenic zebrafish Tg ( fli1 : EGFP) were used to explore the effects of TBT exposure on vascular development. It was found that TBT exposure could lead to impaired development of intersegmental vessels (ISVs), common cardinal vein (CCV), subintestinal vessels (SIVs) and cerebrovascular. The expression of vascular endothelial growth factor (VEGF) signaling pathway-related genes ( flt1 , flt4 , kdr , vegfa ) was downregulated. Biochemical indices showed that ROS and MDA levels were significantly elevated and that SOD and CAT activities were significantly reduced. The expression of key genes for prostacyclin synthesis ( pla2 , ptgs2a , ptgs2b , ptgis , ptgs1 ) is abnormal. Therefore, it is possible that oxidative stress induced by TBT exposure leads to the blockage of arachidonic acid (AA) production in zebrafish embryos, which affects prostacyclin synthesis and consequently the normal development of the heart and blood vessels in zebrafish embryos.
研究领域:
环境毒理学
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发育生物学
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水生毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）