Reference - Detail
RRC ID | 11648 |
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Author | Bahadorani S, Mukai S, Egli D, Hilliker AJ. |
Title | Overexpression of metal-responsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity. |
Journal | 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. |
Volume | 31(7) |
Pages | 1215-26 |
Published | 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 |
Times Cited | 26 |
WOS Category | GERIATRICS & GERONTOLOGY NEUROSCIENCES |
Resource | |
Drosophila | 2020-GAL4 and 6219-GAL4 no pdf available |