Protein phosphorylation pathways disruption by pesticides

Abstract

Phosphosites in the human proteome represent an excellent source of potential biomarkers of pesticide toxicity. In fact, experimental animal models as well as in vitro studies have revealed phosphorylation dis- ruption associated to metabolic regulation, hormone signaling, neuronal function and differentiation, cell survival and death. Due to their estrogen-mimicking ability, pesticides are considered as prime etiological suspects of increasing tumor incidence. Evidences of alterations in the signal transduction pathways in- volved in the tumor progression stage of pesticides were also provided. Despite progress in understand- ing the effect of pesticides on the human phospho- proteome and their health outcomes, it remains a complex issue to be studied. By now, the potential impact of pesticides in epigenetic phosphorylation pathways remains poorly explored. In addition, stud- ies involving pesticides mixtures effects are needed. This review updates and provides a comprehensive discussion on the molecular and biochemical events underlying protein phosphorylation pathway dis- ruption caused by pesticides most frequently detected in human tissues and fluids, such as organochlorine pesticides and organophosphates. The link between epidemiological studies and experimental approaches is also considered. Future challenges, such as micro- array phosphoproteome studies to complement gene expression arrays to understand the mechanisms in- volved in pesticide toxicology are briefly discussed. Keywords: