Cunningham, Rebecca2019-08-222019-08-222017-03-142017-02-22https://hdl.handle.net/20.500.12503/27707Purpose: One of the primary characteristics of Parkinson’s disease (PD) is oxidative stress (OS). Men have a higher risk for PD than women. Testosterone, a primary male sex hormone has been implicated in PD, and is a known oxidative stressor. Previous studies in our lab have shown that testosterone exacerbates OS damage in dopaminergic neurons. However, the mechanism by which testosterone increases OS is unknown. We hypothesize that in dopaminergic cells, testosterone increases OS by activating NOX 1, a major OS generator in cells. Methods: To test our hypothesis, we used a dopaminergic cell line (N27 cells). For an oxidative stressor, we used tert-butyl-hydrogen peroxide (H2O2) to induce 20% cell loss prior to testosterone (100nm) administration. NOX1 inhibitors (Apocynin, Diphenyleneiodonium-DPI) were administered before H2O2 exposure. Cell viability was quantified using the MTT assay. Results: Testosterone is only damaging in the presence of OS. DPI, alone, was damaging to N27 cells, hence this was no longer used as a NOX1 inhbitor. Unlike DPI, Apocynin had no effect on cell viability. Further, Apocynin did not alter H2O2-induced cell loss, indicating that H2O2 increases OS via a non-NOX1 mechanism. However, Apocynin blocked testosterone’s damaging effects in an oxidative stress environment. Conclusions: Testosterone-induced cell loss is mediated by NOX1, indicating that NOX1 is involved in testosterone induced OS generation. By understanding testosterone’s mechanism of action, potential therapeutic targets for Parkinson’s disease can be explored.enposter