Exposure to the emerging contaminant Bisphenol A ( ) is ubiquitous and associated with cardiovascular disorders. effect as endocrine disruptor is widely known but other mechanisms underlying heart disease, such as epigenetic modifications, remain still unclear. A compound of green tea, ( ), may act both as anti-estrogen and as inhibitor of some epigenetic enzymes. The aims of this study were to analyze the molecular processes related to impairment of heart development and to prove the potential ability of to neutralize the toxic effects caused by on cardiac health. Zebrafish embryos were exposed to 2000 and 4000a-I1/4g/L and treated with 50 and 100a-I1/4M . Heart malformations were assessed at histological level and by confocal imaging. Expression of genes involved in cardiac development, estrogen receptors and epigenetic enzymes was analyzed by qPCR whereas epigenetic modifications were evaluated by whole mount immunostaining. embryonic exposure led to changes in cardiac phenotype, induced an overexpression of hand2, a crucial factor for cardiomyocyte differentiation, increased the expression of estrogen receptor (esr2b), promoted an overexpression of a histone acetyltransferase (kat6a) and also caused an increase in histone acetylation, both mechanisms being able to act in sinergy. treatment neutralized all the molecular alterations caused by , allowing the embryos to go on with a proper heart development. Both molecular mechanisms of action (estrogenic and epigenetic) likely lying behind cardiogenesis impairment were successfully counteracted by treatment.
Liu Y., Liang Y., Wishart D.S. (2015) PolySearch 2.0: A significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins, and more. Nucleic Acids Res. 2015 Jul 1;43(Web Server Issue):W535-42.
Cheng D., Knox C., Young N., Stothard P., Damaraju S., Wishart D.S. (2008) PolySearch: a web-based text mining system for extracting relationships between human diseases, genes, mutations, drugs and metabolites. Nucleic Acids Res. 2008 Jul 1;36(Web Server Issue):W399-405.
This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $900 million in funding from the federal government.