Investigation of the interaction of ceramide and acyl-coenzyme A with the mitochondrial associated protein, endozepine, using heteronuclear NMR

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dc.contributor.advisorPugh, David J.R.
dc.contributor.authorOnyemata, Ezenwa James
dc.contributor.otherDept. of Botany
dc.contributor.otherFaculty of Science
dc.date.accessioned2013-08-14T11:51:19Z
dc.date.accessioned2024-05-09T07:46:10Z
dc.date.available2007/06/19 05:40
dc.date.available2007/06/19
dc.date.available2013-08-14T11:51:19Z
dc.date.available2024-05-09T07:46:10Z
dc.date.issued2005
dc.descriptionMagister Scientiae - MScen_US
dc.description.abstractEndozepine is an alternative name for the testis-specific isoform of the acyl-CoA binding protein (t-ACBP). Acyl-CoA binding proteins form a highly conserved family of proteins, which bind long chain fatty acid esters with nanomolar affinity. They are also known to be endogenous ligands to the --amino butyric acid (GABA) receptor in the central nervous system and to play a role in a wide variety of cellular functions such as vesicular trafficking, fatty acid biosynthesis and gene regulation. A role for endozepine in apoptosis was suggested through promoter gene trapping studies using CHO22 cells in which 90 % reduction in the expression of endozepine correlated with delayed mitochondrial permeabilization, a reduced activation of caspase-3 (an activator of apoptosis) and a consequent resistance to C2-ceramide induced apoptosis. Transduction studies using Tat-GFP-ELP fusion protein showed that endozepine restored the sensitivity of mutant CHO22 cells to C2-ceramide induced apoptosis. In this thesis, we have investigated two hypotheses for the involvement of endozepine in ceramide-induced apoptosis. The first hypothesis is that endozepine contributes to apoptosis through the transport of palmitoyl-CoA, a substrate required for the de novo synthesis of ceramide. The second hypothesis is that endozepine interacts directly with ceramide leading to interaction with peripheral benzodiazepine receptor and a subsequent opening of the mitochondria permeability transition pore, leading to apoptosis.en_US
dc.description.countrySouth Africa
dc.identifier.urihttps://hdl.handle.net/10566/13396
dc.language.isoenen_US
dc.publisherUniversity of the Western Capeen_US
dc.rights.holderUniversity of the Western Capeen_US
dc.subjectCeramideen_US
dc.subjectAcyl-coenzyme Aen_US
dc.subjectEndozepineen_US
dc.subjectHeteronuclear NMRen_US
dc.titleInvestigation of the interaction of ceramide and acyl-coenzyme A with the mitochondrial associated protein, endozepine, using heteronuclear NMRen_US
dc.typeThesisen_US

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