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Characterising the Drosophila extracellular superoxide Dismutase gene

Blackney, Michael James (2010) Characterising the Drosophila extracellular superoxide Dismutase gene University of Southampton, School of Biological Sciences, Doctoral Thesis , 270pp.

Record type: Thesis (Doctoral)


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.

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Published date: 30 September 2010
Organisations: University of Southampton


Local EPrints ID: 179761
PURE UUID: 20583109-f879-4d8f-8e04-8353b241e616

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Date deposited: 07 Apr 2011 13:53
Last modified: 18 Jul 2017 12:02

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Author: Michael James Blackney
Thesis advisor: JOEL PARKER

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