Characterization and sensitization of BAX translocation in response to heat-induced apoptosis in tumour cells

Livingstone, Aaron
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University of Guelph

The major initiating event of apoptosis is the conformational change of Bax from an inactive cytoplasmic monomer to a potent inducer of outer mitochondrial membrane permeabilization. How this occurs in response to heat shock is poorly understood, but is paramount to designing tumour-targeted therapies. This thesis examines factors governing the difference in heat sensitivity of two cell lines, a human acute lymphoblastic T cell line (PEER) and a human epithelial cervical carcinoma cell line (HeLa). The ability of conditions, such as low extra-cellular pH, NHE1 inhibition, and modifying protein damage, to modulate Bax activation are explored using a HeLa cell line inducibly over-expressing a yellow fluorescent protein (YFP) - Bax fusion protein. Low extra-cellular pH, NHE1 inhibition and expression of an expanded poly-glutamine protein in conjunction with proteasomal inhibition all sensitize cells to heat-induced apoptosis, suggesting that exploiting tumour biology may be an effective means to facilitate tumour cell death.

initiating event, apoptosis, conformational change, BAX translocation, heat sensitivity, human acute lymphoblastic T cell line, human epithelial cervical carcinoma cell line, HeLa