Date of Award

Summer 2014

Degree Type

Thesis

Degree Name

MS Biology

Department

Biology

Advisor

Jane L. Ko, PhD

Committee Member

Constantine Bitsaktsis, PhD

Committee Member

Jessica Cottrell, PhD

Keywords

DFO, hyoxia, MOR, SOCS

Abstract

While diseases such as cancer and diabetes, or surgery and traumatic injury can cause hypoxia through a decrease in blood circulation to bodily regions or decrease cardiac output they can also associate with hypoxia-induced pain. Clinically, opioids, such as morphine, are used to modulate pain. The mu-opioid receptors (MORs) are one of three main types of opioid receptors and are key mediators in morphine-induced analgesia. Therefore, in this study, the effect of hypoxia on MOR gene expression was examined using human neuronal cells treated with DFO to create a hypoxic-mimic condition. We found that MOR expression was shown to decrease over increased exposure times to DFO. Recently, our laboratory reported that receptor associated C kinase (RACK-1), interacting with the transcription regulator Poly C Binding Protein (PCBP-1), can negatively regulate MOR gene expression using a yeast two-hybrid screening system. RT-PCR analysis revealed an increased in RACK-1 expression while a decrease in MOR expression under DFO treatment was observed. These results supported our recent finding that RACK-1 participates in the regulation of MOR expression. Neuronal cells surviving the DFO insult also displayed activation of the JAK/STAT pathway through Western blot analysis. Due to activation, the suppressors of cytokine signaling (SOCS) proteins, negative regulators of the JAK/STAT pathway, were investigated and detected via RT-PCR. These results suggest that there is an up-regulation of the SOCS proteins under hypoxia, and it may play a role in a form of neuroprotection by aiding in the decrease of inflammation associated with the JAK/STAT pathway.

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