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Date of Award
David L. Njus
The formation of low-potential, highly reactive dopamine oxidation products in the substantia nigra promotes cell death via mechanisms that have yet to be established. To identify the main pathway that is responsible for the cytotoxicity, extensive analysis of aminochrome and 5-cysteinyldopamine was done. It was found that aminochrome forms reactive oxygen species more readily than 5-cysteinyldopamine by redox-cycling with molecular oxygen. To be able to carry out experiments in vivo to efficiently test the low-potential products' effects on cells and how they promote cell death, 3-methyl-5-anilino-1,2-benzoquinone (3-MAQ) was synthesized to act as an analogue of aminochrome and possibly also 5-cysteinyldopamine's oxidation products. Experiments demonstrating the cytotoxicity of 3-MAQ were carried out in vivo using mouse embryonic fibroblasts. In conclusion, we have found that thiols such as cysteine protect against aminochrome's formation, and we were able to synthesize a compound that can help in the study of aminochrome's effects in vivo.
Asmaro, Karam Paul, "Effects Of Dopamine Oxidation Products In Relation To Oxidative Stress And Parkinson's Disease" (2010). Wayne State University Theses. 13.