A protective role of autophagy in Pb-induced developmental neurotoxicity in zebrafish
- Liu, J., Liao, G., Tu, H., Huang, Y., Peng, T., Xu, Y., Chen, X., Huang, Z., Zhang, Y., Meng, X., Zou, F.
- Chemosphere 235: 1050-1058 (Journal)
- Registered Authors
- Chen, Xiaohui, Huang, Zhibin, Zhang, Yiyue
- Autophagy, Lead, Neurotoxicity, Zebrafish
- MeSH Terms
- Autophagy/drug effects*
- Gene Expression
- Larva/drug effects
- Lead Poisoning, Nervous System/prevention & control*
- Water Pollutants, Chemical/toxicity
- 31561294 Full text @ Chemosphere
Liu, J., Liao, G., Tu, H., Huang, Y., Peng, T., Xu, Y., Chen, X., Huang, Z., Zhang, Y., Meng, X., Zou, F. (2019) A protective role of autophagy in Pb-induced developmental neurotoxicity in zebrafish. Chemosphere. 235:1050-1058.
Lead (Pb) is one of the most toxic heavy metals and has aroused widespread concern as it can cause severe impairments in the developing nervous system. Autophagy has been proposed as an injury factor in Pb-induced neurotoxicity. In this study, we used zebrafish embryo as a model, measured the general toxic effects of Pb, and investigated the effect of Pb exposure on autophagy, and its role in Pb-induced developmental neurotoxicity. Zebrafish embryos were exposed to Pb at concentrations of 0, 0.1, 1 or 10 μM until 4 days post-fertilization. Our data showed that exposure to 10 μM Pb significantly reduced survival rates and impaired locomotor activity. Uptake of Pb was enhanced as the concentration and duration of exposure increased. Inhibition of lysosomal degradation with bafilomycin A1 treatment abolished the suppression of Lc3-II protein expression by Pb. Furthermore, autophagosome formation was inhibited by Pb in the brain. In addition, mRNA expression of beclin1, one of the critical genes in autophagy, were decreased in Pb exposure groups at 72 h post-fertilization. Whole-mount in situ hybridization assay showed that beclin1 gene expression in the brain was reduced by Pb. Rapamycin, an autophagy inducer, partly resolved developmental neurotoxicity induced by Pb exposure. Our results suggest that autophagy plays a protective role in the developmental neurotoxicity of Pb in zebrafish embryos and larvae.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes