Juliana Biro

Date of Award

2012

First Advisor

Susan Mechanic-Myers

Second Advisor

David Myers

Abstract

Ryanodine receptors (RyRs) are a class of intracellular calcium channels present in neurons and muscle tissue which mediate the release of calcium from stores in the endoplasmic or sarcoplasmic reticulum upon activation by various endogenous stimuli. There is evidence to suggest that RyRs play an important role in mediating neurodevelopmental processes in both the central nervous system and the peripheral nervous system, and defects in RyR function may play a role in the development of autism and Alzheimer’s disease. Two organic pollutants, polychlorinated biphenyls (PCBs) and triclosan (TCS) have been shown to have a significant impact on calcium regulation via RyR activation in laboratory tests, and another, bisphenol A (BPA), is suspected of operating in a similar manner. The results of these studies have led some researchers to speculate that there may be a link between the increasing use of neurotoxic substances in agriculture, manufacturing, and personal care products and the troubling rise in neurodevelopmental disorders over the last several decades. This experiment aims to expand on previous research by examining the impact of BPA on RyR function, and investigating whether exposure to multiple agonists has a compounding effect on calcium release in vitro. To achieve this, cells of the murine myoblast cell line C2C12 were grown, differentiated into RyR-expressing myotubes, and exposed to various stimuli. Intracellular calcium concentration was monitored using a fluorescent assay before, during, and after treatment with 1μM of the selected stimulus. The results of this analysis showed that compared to the blank control, fluorescence 2 values increased significantly (p < .05) only in cells exposed to the control agonist caffeine and in those cells exposed to TCS and caffeine in combination. These results indicate that BPA does not show RyR agonist activity at low levels of exposure and that there should be minimal concern regarding the RyR mediated neurotoxicity of both BPA and TCS.

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