title: Effects of zinc and DHA on the epigenetic regulation of human neuronal cells.
abstract: Dietary intake of zinc and omega-3 fatty acids (DHA) have health benefits for a number of human diseases. However, the molecular basis of these health benefits remains unclear. Recently, we reported that zinc and DHA affect expression levels of histones H3 and H4 in human neuronal M17 cells. Here, using immunoblotting and densitometric analysis, we aimed to investigate the effect of zinc and DHA on post-translational modifications of histone H3 in M17 cells. In response to increase in zinc concentration, we observed increase in deacetylation, methylation and phosphorylation of H3 and decrease in acetylation. We also investigated the role of zinc in apoptosis, and found that zinc reduced the levels of the anti-apoptotic marker Bcl-2 while increasing the apoptotic marker caspase-3 levels, correlating with cell viability assays. Conversely, DHA treatment resulted in increase in acetylation of H3 and Bcl-2 levels and decrease in deacetylation, methylation, phosphorylation of H3 and caspase-3 levels, suggesting that DHA promotes gene expression and neuroprotection. Our novel findings show the opposing effects of zinc and DHA on the epigenetic regulation of human neuronal cells and highlight the potential benefit of dietary intake of DHA for management of neurodegenerative diseases.
authors.affiliation: NeuroAllergy Research Laboratory (NARL), School of Life and Environmental Sciences, Deakin University, Geelong, Victoria, Australia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Sadli
authors.forename: M Leigh
authors.initials: ML
authors.lastname: Ackland
authors.forename: Damitha
authors.initials: D
authors.lastname: De Mel
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sinclair
authors.forename: Cenk
authors.initials: C
authors.lastname: Suphioglu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
chemical_list: D015525:Fatty Acids, Omega-3; D006657:Histones; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3; D006655:Histone Deacetylases; D015032:Zinc