AHR-mediated ROS production contributes to the cardiac developmental toxicity of PM2.5 in zebrafish embryos
Autor: | Stanley Aniagu, Yujie Huang, Yan Jiang, Fei Ren, Cheng Ji, Tao Chen |
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Rok vydání: | 2019 |
Předmět: |
Environmental Engineering
Embryo Nonmammalian 010504 meteorology & atmospheric sciences DNA damage NF-E2-Related Factor 2 SOD2 Developmental toxicity Aromatic hydrocarbon receptor 010501 environmental sciences medicine.disease_cause 01 natural sciences medicine Environmental Chemistry Animals Waste Management and Disposal Zebrafish 0105 earth and related environmental sciences chemistry.chemical_classification Gene knockdown Reactive oxygen species biology Chemistry Heart Zebrafish Proteins biology.organism_classification Pollution Cardiotoxicity Cell biology Oxidative Stress Particulate Matter Reactive Oxygen Species Oxidative stress |
Zdroj: | The Science of the total environment. 719 |
ISSN: | 1879-1026 |
Popis: | Recent studies have shown an association between maternal exposure to ambient fine particle matter (PM2.5) and congenital heart defects in the offspring, but the underlying molecular mechanisms are yet to be elucidated. Previously, we demonstrated that extractable organic matter (EOM) from PM2.5 induced heart defects in zebrafish embryos by activating the aromatic hydrocarbon receptor (AHR). Hence, we hypothesized that AHR mediates excessive reactive oxygen species (ROS) production, leading to the cardiac developmental toxicity of PM2.5. To test our hypothesis, we examined AHR activity and ROS levels in the heart of zebrafish embryos under a fluorescence microscope. mRNA expression levels were then quantified using qPCR whereas DNA damage and apoptosis were detected by immunofluorescence. Our results showed that the AHR inhibitor, CH223191 (CH) as well as the ROS scavenger, N-Acetyl-L-cysteine (NAC), significantly mitigated the PM2.5-induced cardiac malformations in zebrafish embryos. Furthermore, both CH and NAC diminished the EOM-elevated ROS generation, DNA damage and apoptosis in the test system. Incidentally, both CH and NAC attenuated the EOM-induced changes in the mRNA expression of genes involved in cardiac development (nkx2.5, sox9b), oxidative stress (nrf2a, nrf2b, gstp1, gstp2, sod2, ho1, cat) and apoptosis (p53, bax). We further confirmed that AHR activity is a necessary condition for EOM-induced ROS generation, DNA damage and apoptosis, through AHR knockdown. However, the ROS scavenger NAC did not counteract the EOM-induced AHR activity. In conclusion, our findings suggest that AHR mediates EOM-induced oxidative stress, resulting in DNA damage and apoptosis, thereby contributing to the cardiac developmental toxicity of PM2.5. |
Databáze: | OpenAIRE |
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