Abstract
Hypoxia is classified as a condition in which a body tissue lacks oxygen. A hypoxic microenvironment naturally occurs within the body, causing the stabilization of transcription factor hypoxia-inducible factor one subunit alpha (HIF-1⍺). Recent studies have shown that HIF 1⍺ stability leads to differential signaling in cells. This is of particular interest in the immune system, which contains cells that travel the whole of the body and must be able to adapt and thrive in every microenvironment. The present study analyzed HIF-1⍺ and hypoxia’s role in differential genetic expression of NF-κB target genes. To examine the difference between HIF-1⍺ stability and hypoxic conditions, cells had the NF-κB pathway activated using PMA and Ionomycin. Cells were then treated for 0h, 1h or 4h, with a HIF-1⍺ stabilizer cobalt chloride (CoCl2) or grown in 5% physiological oxygen. Genetic expression of 22 genes was split into 5 categories: metabolic, inflammatory/cytokine producing, NF-κB inhibiting, cell survival/apoptotic and miscellaneous. These genes were examined using RT-qPCR. Comparison between the treatments suggested that HIF-1⍺ stability alone can differ genetic expression compared to cells under hypoxic stress. Furthermore, genes involving metabolism and inflammation saw upregulation when grown in 5% O2 compared to cells treated with CoCl2 which saw downregulation. Apoptotic genes were found to be downregulated in both cells treated with CoCl2 and those grown in 5% O2. NF-κB inhibiting and cell survival genes saw no change in regulation. These results suggest that hypoxic environments impact genetic expression and that HIF-1⍺ stability is not the only factor impacting genetic expression.
Advisor
Nanfack Minkeu, Ferdinand
Department
Biology
Recommended Citation
Inwood, Ari, "Immunological Transcriptional Regulation Under Hypoxia: A Focus on the NF-κB family" (2025). Senior Independent Study Theses. Paper 11666.
https://openworks.wooster.edu/independentstudy/11666
Disciplines
Immunity | Molecular Genetics | Other Immunology and Infectious Disease
Keywords
Hypoxia, Transcriptional Regulation, NF-kB, HIF
Publication Date
2025
Degree Granted
Bachelor of Arts
Document Type
Senior Independent Study Thesis
© Copyright 2025 Ari Inwood