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: Sepehr Bahadorani, Spencer Mukai, Dieter Egli, Arthur J Hilliker
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 31 Issue 7 Pg. 1215-26 (Jul 2010) ISSN: 1558-1497 [Electronic] United States
• PMID: 18775584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2008 Elsevier Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• Transcription Factors
• transcription factor MTF-1
• Cadmium
• Superoxide Dismutase
• Superoxide Dismutase-1
• Zinc

Topics

• 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)
• Superoxide Dismutase-1
• Transcription Factors (biosynthesis, genetics)
• Zinc (metabolism, toxicity)