The Effect of Endocrine Disruptors on Neuron Development

Abstract

Butyrylcholinesterase (BuChE) activity peaks during a 3 hour time period 24 hours post‐initiation of neural tissue differentiation. However, the exact biological role of BuChE during neural tissue development is still unknown. Di‐n‐butyl phthalate (DBP) and bisphenol A (BPA) are well‐documented environmental contaminants that interact with BuChE. Di‐alkyl phenyl phosphates are known irreversible inhibitors of BuChE. The goal of this research is to determine the role of BuChE in stem cell differentiation. We have developed a human umbilical cord mesenchymal stem cell (HUC‐SC) system to determine the effects of these compounds on protein expression. Differentiating cells were exposed to sub‐lethal concentrations of each inhibitor for 48 hours, collected, and homogenized. Cell lysates were analyzed by 2D‐PAGE for protein expression patterns. Relative changes in protein expression were quantified and identification of differentially expressed proteins was achieved using MALDI‐TOF MS. Regardless of the inhibitor used, we identified two significantly up‐regulated proteins in cell extracts: neuron specific enolase and estrogen specific heat shock protein β‐1 (Hsp β‐1). This suggests that BuChE is critical for the neuron differentiation pathway. The presence of heat shock protein indicates that the cells are under stress from exposure to estrogen mimics. We also identified three other developmentally regulated proteins: calmodulin is up‐regulated while cofilin and galectin are down‐regulated. Supported by grants from CSUPERB and the CSULB Mini Grant Programs