The indiscriminate action of reactive oxygen species (ROS), if left unregulated, has long been considered contributory to a range of disease processes within the animal kingdom and is also a factor associated with ageing. Consequently modifying the molecular mechanisms that regulate ROS levels may prove therapeutic and could also positively affect longevity. One of the key components of this machinery is the superoxide dismutase (SOD) family of enzymes which regulate ROS levels by scavenging the ROS superoxide. Mammals have three distinct SOD enzymes each responsible for managing superoxide levels in different cellular compartments. In Drosophila homologues of two of the mammalian SODs, the intracellular (SOD1) and mitochondrial (SOD2) SODs, have been identified and studied extensively demonstrating a clear link between SOD and oxidative protection and survival. Recently the sequence of a third sod gene, homologous to both the relatively poorly characterised mammalian (sod3) and C. elegans (sod-4) extracellular sod, was identified in Drosophila and is also predicted to locate extracellularly (sod3). To date, no (published) work has been carried out to assess the role of sod3 within insects. This thesis reports the molecular and biochemical characteristics of sod3 in Drosophila. Detailed within are the steps taken to clone the sod3 gene which appears to be expressed as two gene products formed by alternative splicing. Furthermore, a combination of gene expression, proteomic and functional analysis of a number of sod mutants was used to: i) reveal sex specific sod gene expression; ii) validate a sod3 hypomorph mutant; iii) indicate a functional role for sod3 in protection against H2O2 induced oxidative stress; iv) suggest a SOD1-SOD3 co-dependency for maintaining Cu Zn SOD activity; v) demonstrate the appearance of genetic modifiers in the sod3 hypomorph. The findings of this report and further studies on the Drosophila sod3 gene should encourage the re-evaluation of the previous work concerning SOD’s influence on disease states and lifespan regulation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:533333 |
| Date | January 2010 |
| Creators | Blackney, Michael James |
| Contributors | Parker, Joel |
| Publisher | University of Southampton |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://eprints.soton.ac.uk/179761/ |
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