Changes in Zn²⁺ Level Alter Gene Expression in Neuronal SH-SY5Y Cells

Nippert, Kathryn

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Changes in Zn²⁺ Level Alter Gene Expression in Neuronal SH-SY5Y Cells

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Research of transition metal ions has elucidated their importance for biological function. Altered levels of transition metal ions in and out of cells are associated with several disease states. For example, Zn²⁺ dysregulation has been reported in chronic inflammatory disease, diabetes, several cancers, and several neurological disorders including Alzheimer’s Disease (AD) and depression. The underlying mechanisms of how alterations in Zn²⁺ levels impact these disease states is not yet well understood. Given that Zn²⁺ ions act as neuromodulators, are involved in synaptic transmission, and are highly concentrated in brain tissue, understanding the regulation of Zn²⁺ could provide insight into the basic pathophysiology of diseases associated with Zn²⁺ dysregulation. The present research utilized quantitative PCR techniques to investigate the regulation of Zn²⁺ via Zn²⁺ homeostasis related gene expression changes with exposure to Zn²⁺ ions for either 2, 4 or 6 hours. Results showed statistically significant upregulation of Mt1, Mt2, and Mt3, and ZnT1 at 2- and 4-hour time points indicating that these genes may be the first responders to cytotoxic levels of Zn²⁺. Additionally, several other genes such as ZnT7 and Znt9 were upregulated only after 6 hours of Zn²⁺ exposure and ZIP10 was downregulated at this time point. This highlights the coordinated and collaborative regulation of Zn²⁺ ions by regulatory proteins. ZnT7, ZnT9, and ZIP10 expression changes may aid in a return to Zn²⁺ concentration homeostasis following the prevention of Zn²⁺ cytotoxicity by the first responder genes mentioned above.

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