The Epigenetic effects of Metals: how the action of mercury goes beyond them.

Epigenetic is the study of modification of the genes leading to the control and regulation of their expression without the involvement of mutagenic events. Epigenetic modifications include DNA methylation, histone modification, RNA regulation, DNA repair, miRNAs-controlled transcription, RNA stability, alternative RNA splicing, protein degradation, gene copy number, and transposon activation; all these processes contribute to the control of gene expression. Primary human keratinocytes (HK), provided by the "Istituto Zooprofilattico di Brescia", were cultured in Epilife Medium supplemented with Keratinocytes supplement, Penicillin and Streptomycin (Sigma). Cells were plated at a density of 1 x 106 in Petri dishes, incubated in a humidified atmosphere of 95% air and 5% CO2 at 37°C and used when 95% confluent. Cells were treated with Mercury Chloride at 10 nM final concentration for 24 hours. In our studies we found that Mercury (HgCl2) was able to inhibit at sub-cytotoxic nanomolar concentrations the gap junction-mediated intercellular communication (GJIC) in cultured Human Keratinocytes determining also reduction of pro-inflammatory interleukins release [3,4]. Furthermore we demonstrated that the Mercury-induced alterations of GJIC were mediated by increased cellular ROS production and reversed by all trans retinoic acid (ATRA) or Lycopene. To note all the Mercury-induced events did not result from any mutagenic effect strengthening the notion that epigenetics is a complex, reversible and multi-faceted/level phenomena