Overexpression of metal-responsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity
Overexpression of metal-responsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity
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DOI：
10.1016/j.neurobiolaging.2008.08.001
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发表时间：
2010-07-01
影响因子：
4.2
通讯作者：
Hilliker, Arthur J.
中科院分区：
文献类型：
--
作者：
Bahadorani, Sepehr;Mukai, Spencer;Hilliker, Arthur J.
重金属是许多生物过程的基本成分，但在高浓度时是有毒的。我们的结果表明，当金属反应转录因子(MTF-1)突变破坏金属动态平衡时，寿命缩短。相反，过表达MTE-1会导致抗性果蝇在补充铁或镉的基础上寿命延长，但在补充锌的基础上寿命缩短。这种作用是通过MTF-1在特定组织中的过度表达而起作用的，例如肠道、血细胞，特别是神经元，这表明这些组织对金属稳态的扰动特别敏感。此外，MT基因以神经元特异性的方式表达，可以保护果蝇免受高氧的伤害，并延长铜/锌超氧化物歧化酶缺陷果蝇的寿命，这表明存在一种共同的机制来保护果蝇免受氧化应激和金属毒性的影响。最后，当MTF-1在周围神经系统或运动神经元中过表达时，正常寿命延长了40%。这些结果证明了重金属毒性和氧化损伤在衰老和寿命决定中的组织特异性输入。(C)2008 Elsevier Inc.保留所有权利。
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, MTE-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, MTPoverexpression 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 motorncurons. These results document the tissue-specific import of heavy metal toxicity and oxidative damage in aging and life-span determination. (C) 2008 Elsevier Inc. All rights reserved.