title: Overexpression of metal-responsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity.
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.
authors.affiliation: Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
authors.forename: Sepehr
authors.initials: S
authors.lastname: Bahadorani
authors.forename: Spencer
authors.initials: S
authors.lastname: Mukai
authors.forename: Dieter
authors.initials: D
authors.lastname: Egli
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Hilliker
mesh_terms: D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics*; D055786:Gene Knockout Techniques; D008136:Longevity / Q000187:drug effects / Q000235:genetics*; D009154:Mutation; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015032:Zinc / Q000378:metabolism / Q000633:toxicity*; D000097809:Transcription Factor MTF-1
chemical_list: D002104:Cadmium; D004268:DNA-Binding Proteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1