The thioredoxin redox charge as a measure of cell redox homeostasis in Schizosaccharomyces pombe.
| dc.contributor.advisor | Pillay, Che Sobashkar. | |
| dc.contributor.author | Bhagwandeen, Tejal. | |
| dc.date.accessioned | 2023-08-23T19:31:15Z | |
| dc.date.available | 2023-08-23T19:31:15Z | |
| dc.date.created | 2022 | |
| dc.date.issued | 2022 | |
| dc.description | Masters Degree. University of KwaZulu-Natal, Pietermaritzburg. | en_US |
| dc.description.abstract | Thiol-based redox systems play essential roles in repairing oxidatively damaged proteins, deoxyribonucleotide synthesis, sulfur metabolism, protein folding, and oxidant detoxification and signaling. The principal thiol systems in most cells are the thioredoxin (Trx) and the glutathione/glutaredoxin (GSH/Grx) systems. In the thioredoxin system, reducing equivalents from NADPH are transferred by thioredoxin reductase to thioredoxin, resulting in reduced thioredoxin. Thioredoxin in the reduced form further reduces target proteins and is itself consequently oxidized. Given the system’s essential role in cellular physiology, inhibition of the thioredoxin system is an important drug target for communicable and non-communicable diseases. However, measuring the activity of the thioredoxin system in vivo is challenging. The thioredoxin redox charge (reduced thioredoxin/total thioredoxin) was proposed as a novel, surrogate measure of the thioredoxin system’s activity and could be used as a general measure of the cellular redox state. Indeed, published data showed that the thioredoxin redox charge and cell viability collapsed if a chemical inhibitor directly targeted thioredoxin reductase. To evaluate the utility of the thioredoxin redox charge as a generic indicator of redox stress, the fission yeast Schizosaccharomyces pombe, was subjected to various stressors including hydrogen peroxide, heat, cadmium sulfate and potassium ferricyanide and the thioredoxin redox charge and cell viability were measured over time. We found dynamic changes in the thioredoxin redox charge profiles, in response to these stressors, but only obtained weak, positive correlations between the thioredoxin redox charge and cell viability. Thus, and in contrast to our initial hypothesis, the thioredoxin redox charge appeared to be buffered in response to high-stress perturbations, even when cell viability was clearly inhibited. These results show that the redox poise of the thioredoxin system can presumably only be disrupted by direct inhibitors of the system. Future work should aim to elucidate the mechanisms underlying the preservation of the thioredoxin redox charge. | en_US |
| dc.identifier.uri | https://researchspace.ukzn.ac.za/handle/10413/22158 | |
| dc.language.iso | en | en_US |
| dc.subject.other | Cell viability. | en_US |
| dc.subject.other | Thiol-based redox systems. | en_US |
| dc.title | The thioredoxin redox charge as a measure of cell redox homeostasis in Schizosaccharomyces pombe. | en_US |
| dc.type | Thesis | en_US |