RRC ID 11648
著者 Bahadorani S, Mukai S, Egli D, Hilliker AJ.
タイトル Overexpression of metal-responsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity.
ジャーナル Neurobiol Aging
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.
巻・号 31(7)
ページ 1215-26
公開日 2010-7-1
DOI 10.1016/j.neurobiolaging.2008.08.001
PII S0197-4580(08)00280-7
PMID 18775584
MeSH Animals Cadmium / metabolism Cadmium / toxicity* DNA-Binding Proteins / biosynthesis* DNA-Binding Proteins / genetics Drosophila melanogaster / drug effects Drosophila melanogaster / genetics* Gene Knockout Techniques Longevity / drug effects Longevity / genetics* Mutation* Nervous System / drug effects Nervous System / metabolism Neurons / drug effects Neurons / metabolism Oxidative Stress / drug effects Oxidative Stress / genetics* Stress, Physiological / drug effects Stress, Physiological / genetics Superoxide Dismutase / genetics Superoxide Dismutase / metabolism Superoxide Dismutase-1 Transcription Factors / biosynthesis* Transcription Factors / genetics Zinc / metabolism Zinc / toxicity*
IF 4.347
引用数 26
WOS 分野 GERIATRICS & GERONTOLOGY NEUROSCIENCES
リソース情報
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