Citation:

Kodavanti, P. Neurotoxicity of Legacy and Emerging Persistent Organic Chemicals: A Proteomic Approach to Understand Adverse Outcome Pathways. International Symposium on Halogenated Persistent Organic Pollutants, Vancouver, BC, CANADA, August 20 - 25, 2017.

Impact/Purpose:

Invited expert lecture at a scientific meeting. The talk is topical with no new data presented.

Description:

During the past century, a vast number of persistent organic chemicals (POCs) have been manufactured and used in industrial, agricultural, public health, consumer products and other applications. Widespread use of legacy POCs, including chlorinated, brominated and fluorinated compounds, lead to environmental contamination and human exposures occurring through multiple pathways such as direct skin contact, inhalation, drinking water, and food. Exposure to these POCs has been implicated in myriad human health effects including neurotoxicity at environmentally relevant concentrations. Polybrominated diphenyl ethers (PBDEs), perfluorinated chemicals (PFCs), triclosan, triclocarban, tetrabromobishphenol A (TBBPA), hexabromocyclododecane (HBCD), and organophosphate flame retardants are considered as some of the emerging POCs of environmental concern [1]. Based on their use pattern and their persistent chemical properties, it can be predicted that human exposure to these compounds will continue. Human health effects due to such exposures also continue to be an issue of concern. We have focused on POCs that are legacy compounds such as polychlorinated biphenyls (PCBs) which were banned, but were previously used as heat transfer fluids in transformers and other industrial applications. Polybrominated diphenyl ethers (PBDEs) which belong to brominated flame retardant family of chemicals are considered as emerging POCs. PCBs are PBDEs are structurally similar to PCBs with a similar number of congeners with different position and number of halogens. Both these chemicals are well established developmental neurotoxicants in both humans and animal models [2]. At the functional level, effects include deficits in learning and memory as well as psychomotor disturbances. At structural levels, the effects include decreased neuronal branching pattern and dendritic growth. We have focused on understanding the adverse outcome pathways for neurotoxicity utilizing the proteomic technologies. Our neuroproteomic data using 2-dimentional gel electrophoresis (DIGE) followed by analysis, and identification of protein spots by MassSpec have revealed that proteins related to energy metabolism (ATP synthase, sub unit β, creatine kinase B-type, and malate dehydrogenase), calcium signaling (endoplasmic reticulum ATPase, voltage-dependent anion-selective channel protein 1, myristoylated alanine-rich-C-kinase, and Ryanodine receptor type II), and growth of the nervous system (valosin-containing protein, collapsin response mediator protein 3, Dihydropyrimidinase-related protein) were altered by developmental exposure to these two chemicals. Although different proteins were differentially expressed by PCBs and PBDEs, the pathways affected were similar, suggesting common adverse-outcome pathways within this extended family of chemicals [3]. These results should be extended to other POCs of concern with regard to neurotoxicity and for identification of common protein signatures and pathways.

Record Details: