Metilmercúrio e neurodesenvolvimento: uma abordagem de biologia de sistemas

Abstract

Bacteria metabolize mercury into its organic derivative, methylmercury (MeHg), which is toxic, bioaccumulative, and has the ability to cross the hematoencephalic and placental barriers. MeHg exposure is associated with neurodevelopmental impairments. Human contamination is a worldwide phenomenon and occurs mainly through fish comsumption. The interaction of MeHg with target proteins or metabolic processes might enlighten us as to the mechanisms through which MeHg acts. Our objective was to apply a systems biology approach, analyzing PPI networks constructed from literature data. We aimed at finding target proteins, associated with particular processes, whose perturbation would probably rupture the network. A systematic review was performed, in which 182 studies were found. A list of 169 proteins was extracted from those studies and its IDs were uploaded to the String-DB database in order to assemble a protein-protein interaction network. The network properties were evaluated through cluster, enrichment and topology analyses using Cytoscape v 3.7.0 and R. Our results suggest the most important process associated with MeHg in utero exposure and neurodevelopment is cellular signaling. In addition, not only this is the most prominent process in the main network, but also the target proteins found (RAC1, CDC42, AKT1, MAPK3, MAPK1) are included in this particular group. Our findings may help focusing research and elucidating the mechanisms of MeHg toxicity. Hopefully it might also contribute to the future development of new treatment or prophylactic measures to avoid neurodevelopmental damage following MeHg exposure.