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Physical Sciences and Mathematics

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University of Wisconsin Milwaukee

Theses and Dissertations

2020

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Intracellular Zinc Trafficking: An Interplay Of Proteome, Metallothioneine And Glutathione, Afsana Mahim May 2020

Intracellular Zinc Trafficking: An Interplay Of Proteome, Metallothioneine And Glutathione, Afsana Mahim

Theses and Dissertations

Zinc is the second most abundant transition metal in living organisms. Typically, a eukaryotic cell contains approximately 3000 zinc binding proteins, in which zinc plays structural or catalytic roles. Recently, zinc has been reported to have signaling functions as a secondary messenger. Considering the diverse cellular functions of zinc, the trafficking pathways that help zinc, following its uptake into cytosol, find the target proteins and generate native Zn-Proteins are not well-understood. For past few decades, metallothionein, a zinc binding protein with large stability constants for Zn2+, has been thought of as a mediator in transferring zinc to apo-Proteins. However, gene …


Zinc Proteomics: Interactions Of Zn2+, Cd2+, And Metal-Binding Ligands With Zn-Binding Sites In The Proteome, Eric Daniel Lund May 2020

Zinc Proteomics: Interactions Of Zn2+, Cd2+, And Metal-Binding Ligands With Zn-Binding Sites In The Proteome, Eric Daniel Lund

Theses and Dissertations

Cadmium ion causes toxicity in humans, most prominently in the kidney. This thesis focuses on mechanisms by which Cd2+ harms kidney proximal tubule cells. Previous experiments have shown the time-dependent distribution of Cd2+ and Zn2+ within supernatant of pig kidney, LLC-PK1 cells after exposure to Cd2+ plus the ionophore pyrithione1. The first part of this research describes the trafficking of cadmium within LLC-PK1 proximal tubule cells, including the time dependent distribution, speciation, and quantification of Cd2+ and Zn2+ in cells exposed to Cd2+ and Cd2+ plus pyrithione. The latter treatment introduces Cd2+ into cells at time zero and permits the …