Date of Award

Spring 3-1-2022

Degree Type

Thesis

Degree Name

MS Biology

Department

Biology

Advisor

Jessica Cottrell, Ph.D.

Committee Member

Daniel B Nichols, Ph.D.

Committee Member

Constantine Bitsaktsis, Ph.D.

Keywords

Sodium Orthovanadate, Senescence, Giant multinucleated cells, SASP, inflammation, Senolytics

Abstract

Cellular senescence is considered a signal transduction process where damaged or stressed cells arrest proliferation. Exogenous stressors including bacterial infection, chemotherapy, and irradiation can drive normal cells to senescence. Sodium orthovanadate (Na3VO4) is a phosphatase inhibitor known to mediate the release of the proinflammatory cytokine, TNF-a. We hypothesized that NaVO4 treatment will reduce proinflammatory expression from senescent cells. In our study we illustrate that prolonged exposure to LPS caused RAW 264.7 cells induced morphological changes indicative of senescent cells including the formation of giant multinucleated cells (GMCs). Furthermore, we found that RAW 264.7 GMC cells stain positive for senescence and increase expression of key proinflammatory cytokines associated with the senescent phenotype including IL-10 and TNF-α. Our data demonstrate that 100uM and 1000uM sodium orthovanadate treatment reduced cell proliferation. The reduction in proliferation was concomitant with changes in pro-inflammatory cytokines, IL-10, and TNF-α (Figure 9B &C at 24hrs). IPA analysis confirmed connections between these proinflammatory cytokines, senescence, and disease progression.

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