Date of Award

Summer 7-1-2019

Degree Type

Thesis

Degree Name

MS Biology

Department

Chemistry and Biochemistry

Advisor

Dr. Jane Ko

Committee Member

Dr. Tin-Chun Chu

Committee Member

Dr. Daniel Nichols

Committee Member

Dr. Angela Klaus

Committee Member

Dr. Heping Zhou

Keywords

hypoxia, nickel, cobalt, flow cytometry, hypoxic

Abstract

Hypoxia is an imbalance in oxygen delivery and oxygen consumption, ultimately affecting cell survival. Low levels of oxygen diminish adenosine triphosphate synthesis resulting from a decline in oxidative phosphorylation in the mitochondria, therefore inducing apoptosis and cell death. To create a hypoxia mimicked environment, we used hypoxia mimetic compounds cobalt and nickel to treat human neuroblastoma (NMB) cells. Using hypoxic mimic human neuronal cell models, we examined and compared the effects of compound-induced hypoxia on NMB cell proliferation. The cells were treated with 100mM and 300mM concentrations of each compound at 24- and 48-hour intervals. To investigate cell proliferation, the thymidine analog EdU was used, which incorporates into DNA during DNA synthesis. Flow Cytometry was used to measure and analyze the fluorescence of EdU incorporation. Results showed the inhibition of cell proliferation using both nickel and cobalt treated cells as compared to the control cells with no treatment. Furthermore, the inhibition of cell proliferation was dependent upon the exposure time and concentration dose. Interestingly under the same concentration, cobalt produced greater inhibition of cell proliferation than nickel. Although the causes of differences are unclear currently, possible reasons are discussed and hypothesized. In conclusion, this study demonstrated differences in the inhibition of cell proliferation using nickel or cobalt hypoxic mimetic compounds in human neuronal cells. Further research to determine mechanisms behind different cell models will provide additional information and understanding in regard to hypoxia related diseases.

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