Date of Award

January 2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Psychology

First Advisor

Scott Garrett

Abstract

Metallothioneins (MT) are low molecular weight, cysteine-rich, metal-binding proteins that protect against metal toxicity. MTs have several functions, such as transport of metals, detoxification of metals, and protection from metal toxicity. MT-3, first called growth inhibitory factor, was originally discovered as the Alzheimer’s disease gene. MT-3 has a unique structure with 7 additional amino acids. The role of MT-3 is unknown. Some studies suggest MT-3 plays a role in the immune system and with cisplatin resistance. RPTEC/TERT1 cell line is an immortalized cell line from the human proximal tubule of an adult kidney. It was determined that RPTEC/TERT1 cultures consisted of two CD24-expressing cell types, one that co-expresses PROM1 and CD24 (HRTPT), and another expressing only CD24 (HREC24T). The UROtsa cell line was derived from the urothelium that lines the ureter and was immortalized. UROtsa cells have been malignantly transformed by prolonged exposure to the environmental toxicant arsenite (As_I). The first goal of this study was to examine the effect of cadmium and cisplatin on MT-3 overexpressed cells in the HRTPT and UROtsa As_I cell lines to further understand cisplatin resistance. The results showed no indication of cisplatin resistance for either cell line. The second goal of this study was to determine the role of MT-3 in both UROtsa As_I and HRTPT cell lines. RNA-seq results showed a common pathway of inflammatory response for both UROtsa As_I and HRTPT cell lines.

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