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Drosophila melanogaster as a model organism for understanding the interrelationship of micronutrient antioxidants and atmospheric oxidative stress

Posted on:2006-07-17Degree:Ph.DType:Dissertation
University:University of California, DavisCandidate:Wilson, MalindaFull Text:PDF
GTID:1450390005492814Subject:Environmental Sciences
Abstract/Summary:
Studies of Drosophila melanogaster have led to insights concerning biomolecular mechanisms of biology and disease. Although Drosophila's antioxidant enzyme systems are well characterized, less information is available concerning their micronutrient antioxidant systems.; Wild-type (Canton S) Drosophila, unlike vertebrate mammals, selectively retains gamma-tocopherol over alpha-tocopherol. Drosophila displayed detectable levels of alpha- and gamma-tocopherol in proportions reflecting the composition of the standard diet, and provision of supplemental alpha- or gamma-tocopherol lead to increases in Drosophila tissue levels. Genomic analysis revealed that Drosophila possess genes related to the mammalian alpha-tocopherol transfer protein (alpha-TTP) that differ slightly in the predicted tocopherol binding pocket, and may explain the selective uptake and retention of gamma-tocopherol over alpha-tocopherol in Drosophila.; Urate-deficient (ry531 strain) Drosophila had <2% of the urate levels of wild-type Drosophila had 50% of the ascorbate levels. Dietary supplementation with ascorbate increased its level while chemically-defined diets led to rapid depletion of ascorbate. Like most mammalian species, large dietary excesses of ascorbate appear to be readily excreted by Drosophila and only a small fraction being equilibrated within body stores. From this data, it is concluded that Drosophila , similar to humans, do not synthesize ascorbate.; Wild-type and urate-deficient Drosophila were continuously exposed to O3 (2, 5 and 10 ppm) over their entire lifespan. Exposure of Drosophila to 2 PPM O3/24hrs/day unmasked a marked sensitivity phenotype of urate-deficient Drosophila. O3 exposure resulted in increased levels of 4-hydroxynonenal (4-HNE) in both Drosophila strains and urate-deficient Drosophila showed a susceptibility to increased levels of oxidized products of linoleic acid.; Studies revealed that ascorbate supplementation decreased O3-induced toxicity in Drosophila. Wild-type Drosophila were continuously exposed to 2 PPM O3 and daily dietary provision of ascorbate during O3 exposure resulted in the development of O3 resistance with respect to mortality. DNA microarray analysis revealed that O3 exposure results in the up-regulation of numerous genes primarily related to hose defense/stress response, immune functions and metabolism. Differential gene expression analysis revealed that ascorbate supplementation modulated the expression of O3-responsive genes.; Collectively, these data reveal the usefulness of Drosophila as a model organism for studying micronutrient antioxidants and their interrelationship with O3-induced toxicity.
Keywords/Search Tags:Drosophila, Micronutrient, O3 exposure, Ascorbate
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