Date of Award

Winter 12-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

Department/Program

Forensic Science

Language

English

First Advisor

Shu-Yuan Cheng

Second Reader

Anthony Carpi

Third Advisor

Juan Zhen

Abstract

Environmental factors, such as heavy metal exposures, have been suggested to have an impact not only on neurodegenerative disease, such as Parkinson’s disease, but also on psychostimulants abuse and their toxicity. In this study, two questions were addressed: 1) effects of mercuric chloride on parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP+) induced cytotoxicity and 2) effects of mercuric chloride on cell surface dopamine transporter. Pheochromocytorma cells (PC12) were treated with various concentrations of mercuric chloride (0.02~2.0 ppm) for 4 hours with and without 0.1 mM MPP+. Significant potentiation of toxicity was observed when there was co-treatment with 0.5 ppm HgCl2 and 0.1mM MPP+ vs. HgCl2 alone. The potentiation of toxicity with the co-treatment of 0.5 ppm mercuric chloride and 0.1mM MPP+ was not observed in PC12 cells expressing DAT mutant L368Q, which has impaired uptake activity. Cell surface expression of dopamine transporter was quantitatively seen to be transiently increased via western blot analysis which was correspondingly visualized via immunocytochemical assay. In summary, mercuric chloride enhanced MPP+ toxicity in a dopamine transporter-dependent manner and increased the surface expression of dopamine transporter in PC12 cells. This toxicological effect of mercury on dopamine transporter could trigger an unpredicted toxicological/pharmacological interaction with drugs affecting the dopaminergic system.

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