Effects of DFO-Induced Hypoxia on Key Signaling Mediators

<p>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.</p>

Name thesis:degree_name

MS Biology

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2014

Author dc:creator

• Candelora, Jennifer

Contributors dc:contributor

• Jane L. Ko, PhD
• Constantine Bitsaktsis, PhD
• Jessica Cottrell, PhD

• DFO
• hyoxia
• MOR
• SOCS
• Medicine and Health Sciences
• Neuroscience and Neurobiology

Repository record dc:identifier

https://scholarship.shu.edu/dissertations/1982

OAI identifier oai:identifier

oai:scholarship.shu.edu:dissertations-2993