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 disruption ...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 disruption 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 involved in the tumor progression stage of pesticides were also provided. Despite progress in understanding the effect of pesticides on the human phosphorproteome 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, studies involving pesticides mixtures effects are needed. This review updates and provides a comprehensive discussion on the molecular and biochemical events underlying protein phosphorylation pathway disruption 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 involved in pesticide toxicology are briefly discussed.展开更多
Phospholipid and phosphoinositide phosphorylation pathways have been shown to be of crucial importance on producing lipid mediators. The earlier findings reported on lipid molecules playing roles in different metaboli...Phospholipid and phosphoinositide phosphorylation pathways have been shown to be of crucial importance on producing lipid mediators. The earlier findings reported on lipid molecules playing roles in different metabolic pathways used to assign them the exclusive role of second messenger generators. Several researchers have recently described how direct interaction of phospholipids and phosphoinositides with molecules or organelles, without the need for producing second messenger molecules, is responsible for their mechanism of action. Organophosphate and organochlorine pesticide toxicity mechanisms have been extensively studied in relation to their well known effects on cholinesterase activities and on the alterations of electric activity in the nervous system of different organisms respectively. There is little but consistent evidence that some compounds, including in both groups of pesticides, are also able to interact with phospholipid and phosphoinositide phosphorylation pathways in several organisms and tissues. The present review consists of an actualization of basic research on phospholipid and phosphoinositide phosphorylation and hydrolysis pathways, as well as a description of some reported evidences for the effects of the above mentioned pesticides on them.展开更多
文摘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 disruption 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 involved in the tumor progression stage of pesticides were also provided. Despite progress in understanding the effect of pesticides on the human phosphorproteome 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, studies involving pesticides mixtures effects are needed. This review updates and provides a comprehensive discussion on the molecular and biochemical events underlying protein phosphorylation pathway disruption 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 involved in pesticide toxicology are briefly discussed.
文摘Phospholipid and phosphoinositide phosphorylation pathways have been shown to be of crucial importance on producing lipid mediators. The earlier findings reported on lipid molecules playing roles in different metabolic pathways used to assign them the exclusive role of second messenger generators. Several researchers have recently described how direct interaction of phospholipids and phosphoinositides with molecules or organelles, without the need for producing second messenger molecules, is responsible for their mechanism of action. Organophosphate and organochlorine pesticide toxicity mechanisms have been extensively studied in relation to their well known effects on cholinesterase activities and on the alterations of electric activity in the nervous system of different organisms respectively. There is little but consistent evidence that some compounds, including in both groups of pesticides, are also able to interact with phospholipid and phosphoinositide phosphorylation pathways in several organisms and tissues. The present review consists of an actualization of basic research on phospholipid and phosphoinositide phosphorylation and hydrolysis pathways, as well as a description of some reported evidences for the effects of the above mentioned pesticides on them.
