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Histological Analyses of Acute Alcoholic Liver Injury in Zebrafish
Published on: May 25, 2017
Possible molecular mechanism underlying cadmium-induced circadian rhythms disruption in zebrafish
Bo Xiao1, Tian-Ming Chen1, Yingbin Zhong2
1Key Laboratory for Ecology and Pollution Control of Coastal Wetlands, School of Environmental Science and Engineering, Yancheng Institute of Technology, Yancheng 224051, Jiangsu, PR China.
Abstract:
This study was aimed to explore the mechanisms underlying cadmium-induced circadian rhythms disruption. Two groups of zebrafish larvae treated with or without 5 ppm CdCl2 were incubated in a photoperiod of 14-h light/10-h dark conditions. The mRNA levels of clock1a, bmal1b, per2 and per1b in two groups were determined. Microarray data were generated in two group of samples. Differential expression of genes were identified and the changes in expression level for some genes were validated by RT-PCR. Finally, Gene Ontology functional and KEGG pathway enrichment analysis of differentially expressed genes (DEGs) were performed. In comparison with normal group, the mRNA levels of clock1a, bmal1b, and per2 were significantly changed and varied over the circadian cycle in CdCl2-treated group. DEGs were obtained from the light (84 h, ZT12) and dark (88 h, ZT16) phase. In addition, G-protein coupled receptor protein signaling pathway and immune response were both enriched by DEGs in both groups. While, proteolysis and amino acid metabolism were found associated with DEGs in light phase, and Neuroactive ligand-receptor interaction and oxidation-reduction process were significantly enriched by DEGs in dark phase. Besides, the expression pattern of genes including hsp70l and or115-11 obtained by RT-PCR were consistent with those obtained by microarray analysis. As a consequence, cadmium could make significant effects on circadian rhythms through immune response and G protein-coupled receptor signaling pathway. Besides, between the dark and the light phase, the mechanism by which cadmium inducing disruption of circadian rhythms were different to some extent.
Insights
Cadmium exposure disrupts zebrafish circadian rhythms by affecting clock gene expression. These disruptions involve immune response and G-protein coupled receptor signaling pathways, with differing mechanisms between light and dark phases.
Area of Science:
- Environmental toxicology
- Chronobiology
- Molecular biology
Background:
- Circadian rhythms are crucial for biological processes.
- Cadmium is a toxic metal pollutant with potential to disrupt biological functions.
- Understanding cadmium's impact on circadian rhythms is important for public health.
Purpose of the Study:
- To investigate the molecular mechanisms of cadmium-induced circadian rhythm disruption in zebrafish.
- To identify specific genes and pathways affected by cadmium exposure.
- To differentiate the effects of cadmium on circadian rhythms during light and dark phases.
Main Methods:
- Zebrafish larvae were exposed to 5 ppm Cadmium Chloride (CdCl2).
- mRNA levels of key clock genes (clock1a, bmal1b, per2, per1b) were analyzed.
- Microarray analysis identified differentially expressed genes (DEGs).
- Gene Ontology and KEGG pathway enrichment analyses were performed.
- RT-PCR validated the expression patterns of selected genes.
Main Results:
- Cadmium exposure significantly altered the mRNA levels of clock1a, bmal1b, and per2 over the circadian cycle.
- DEGs were identified in both light and dark phases.
- Enriched pathways included G-protein coupled receptor protein signaling and immune response.
- Specific pathways like proteolysis and amino acid metabolism were affected in the light phase, while neuroactive ligand-receptor interaction and oxidation-reduction were affected in the dark phase.
- RT-PCR results confirmed microarray findings for genes like hsp70l and or115-11.
Conclusions:
- Cadmium significantly impacts circadian rhythms in zebrafish, primarily through modulation of immune response and G-protein coupled receptor signaling pathways.
- The mechanisms underlying cadmium-induced circadian disruption differ between the light and dark phases.
- These findings highlight the complex effects of environmental toxins on fundamental biological rhythms.
