Reference - Detail
|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.|
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.
|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*|
|WOS Category||GERIATRICS & GERONTOLOGY NEUROSCIENCES|
|Drosophila||2020-GAL4 and 6219-GAL4 no pdf available|