Authors: Bahadorani S; Mukai S; Egli D; Hilliker AJ
Abstract: Heavy metals are essential components of many biological processes but are toxic at high concentrations. Our results illustrate that when metal homeostasis is compromised by a mutation in the metal-responsive transcription factor (MTF-1), the life-span is shortened. In contrast, MTF-1 overexpression results in resistant flies with prolonged longevity on iron or cadmium-supplemented media but shortened life-span on zinc-supplemented medium. This effect was mediated by the overexpression of MTF-1 in specific tissues, such as the gut, hemocytes and in particular in neurons, indicating that these tissues are particularly sensitive to the perturbance of metal homeostasis. Further, MTF-1 overexpression in a neuron-specific manner protects flies against hyperoxia and prolongs the life-span of Cu/Zn superoxide dismutase-deficient flies, suggesting the presence of a common mechanism for protection against both oxidative stress and metal toxicity. Finally, normal life-span is extended up to 40% upon MTF-1 overexpression in either the peripheral nervous system or motorneurons. These results document the tissue-specific import of heavy metal toxicity and oxidative damage in aging and life-span determination.Keywords: Animals; Cadmium/metabolism/*toxicity; DNA-Binding Proteins/*biosynthesis/genetics; Drosophila melanogaster/drug effects/*genetics; Gene Knockout Techniques; Longevity/drug effects/*genetics; *Mutation; Nervous System/drug effects/metabolism; Neurons/drug effects/metabolism; Oxidative Stress/drug effects/*genetics; Stress, Physiological/drug effects/genetics; Superoxide Dismutase/genetics/metabolism; Transcription Factors/*biosynthesis/genetics; Zinc/metabolism/*toxicity
Journal: Neurobiology of aging
Date: Sept. 9, 2008
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Bahadorani S, Mukai S, Egli D, Hilliker AJ (2010) Overexpression of metal-responsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity. Neurobiology of aging 31: 1215-26.