Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage
- Xu, T., Zhao, J., Hu, P., Dong, Z., Li, J., Zhang, H., Yin, D., Zhao, Q.
- Toxicology and applied pharmacology 277: 183-91 (Journal)
- Registered Authors
- Hu, Ping, Zhao, Qingshun
- Gastrulation, Glycolysis, Oxidative phosphorylation, Pentachlorophenol, Warburg effect, Zebrafish
- MeSH Terms
- Adenosine Triphosphate/metabolism
- Cell Cycle/drug effects
- Dose-Response Relationship, Drug
- Environmental Pollutants/toxicity*
- Gastrula/drug effects*
- Gastrulation/drug effects*
- Gene Expression Profiling/methods
- Gene Expression Regulation, Developmental/drug effects
- Glycolysis/drug effects*
- Oligonucleotide Array Sequence Analysis
- Oxidative Phosphorylation/drug effects*
- Time Factors
- 24642059 Full text @ Tox. App. Pharmacol.
Xu, T., Zhao, J., Hu, P., Dong, Z., Li, J., Zhang, H., Yin, D., Zhao, Q. (2014) Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage. Toxicology and applied pharmacology. 277:183-91.
Pentachlorophenol (PCP) is a prevalent pollutant in the environment and has been demonstrated to be a serious toxicant to humans and animals. However, little is known regarding the molecular mechanism underlying its toxic effects on vertebrate early development. To explore the impacts and underlying mechanisms of PCP on early development, zebrafish (Danio rerio) embryos were exposed to PCP at concentrations of 0, 20 and 50μg/L, and microscopic observation and cDNA microarray analysis were subsequently conducted at gastrulation stage. The morphological observations revealed that PCP caused a developmental delay of zebrafish embryos in a concentration-dependent manner. Transcriptomic data showed that 50μg/L PCP treatment resulted in significant changes in gene expression level, and the genes involved in energy metabolism and cell behavior were identified based on gene functional enrichment analysis. The energy production of embryos was influenced by PCP via the activation of glycolysis along with the inhibition of oxidative phosphorylation (OXPHOS). The results suggested that PCP acts as an inhibitor of OXPHOS at 8hpf (hours postfertilization). Consistent with the activated glycolysis, the cell cycle activity of PCP-treated embryos was higher than the controls. These characteristics are similar to the Warburg effect, which occurs in human tumors. The microinjection of exogenous ATP confirmed that an additional energy supply could rescue PCP-treated embryos from the developmental delay due to the energy deficit. Taken together, our results demonstrated that PCP causes a Warburg-like effect on zebrafish embryos during gastrulation, and the affected embryos had the phenotype of developmental delay.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes