Overexpression of metal-responsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity

Bahadorani, Sepehr; Mukai, Spencer T.; Egli, Dieter; Hilliker, Arthur J.

doi:10.1016/j.neurobiolaging.2008.08.001

Cited by 45 publications

(48 citation statements)

References 49 publications

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“…An earlier study demonstrated that MTF-1 overexpression enhances Drosophila survival to the adult stage on both copper-supplemented and copper-depleted media (Bahadorani et al, 2008b). Here, we hypothesized that ubiquitous overexpression of MTF-1 in our fly model may enhance pupal survival to the adulthood stage.…”

Section: Copper Supplementation and Overexpression Of Mtf-1 Enhances mentioning

confidence: 90%

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A Drosophila model of Menkes disease reveals a role for DmATP7 in copper absorption and neurodevelopment

Bahadorani

Marcon

et al. 2010

Disease Models &Amp; Mechanisms

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SUMMARY Human Menkes disease is a lethal neurodegenerative disorder of copper metabolism that is caused by mutations in the ATP7A copper-transporting gene. In the present study, we attempted to construct a Drosophila model of Menkes disease by RNA interference (RNAi)-induced silencing of DmATP7, the Drosophila orthologue of mammalian ATP7A, in the digestive tract. Here, we show that a lowered level of DmATP7 mRNA in the digestive tract results in a reduced copper content in the head and the rest of the body of surviving adults, presumably owing to copper entrapment in the gut. Similar to Menkes patients, a majority of flies exhibit an impaired neurological development during metamorphosis and die before eclosion. In addition, we show that survival to the adult stage is highly dependent on the copper content of the food and that overexpression of the copper homeostasis gene, metal-responsive transcription factor-1 (MTF-1), enhances survival to the adulthood stage. Taken together, these results highlight the role of DmATP7-mediated copper uptake in the neurodevelopment of Drosophila melanogaster and provide a framework for the analysis of potential gene interactions influencing Menkes disease.

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Section: Copper Supplementation and Overexpression Of Mtf-1 Enhances mentioning

confidence: 90%

“…To increase the efficiency of DmATP7 silencing, a transgenic strain carrying RNAi constructs on both the second and the third chromosome was constructed and crossed to a strain carrying a gut-specific 2020-GAL4 driver. The Tub-MTF-1 transgene expressing MTF-1 has been described previously (Bahadorani et al, 2008b).…”

Section: Construction Of Transgenic Fliesmentioning

confidence: 99%

A Drosophila model of Menkes disease reveals a role for DmATP7 in copper absorption and neurodevelopment

Bahadorani

Marcon

et al. 2010

Disease Models &Amp; Mechanisms

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“…Ctr1B and ZnT35C). Bahadorani et al (2010) showed that, in Drosophila provided a standard diet, systemic over-expression of transcriptional factor of MT, such as MTF-1, had no effect on lifespan. However, over-expression of MTF-1 in hemocytes significantly decreased lifespan, and the opposite effect was observed in the nervous system, with over-expression of MTF-1 leading to significantly increased lifespan by approximately 40% (Bahadorani et al 2010).…”

Section: Zinc Mt and Ageingmentioning

confidence: 99%

Zinc, metallothioneins and immunosenescence: effect of zinc supply as nutrigenomic approach

et al. 2011

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Ageing is an inevitable biological process associated with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Nutritional factor, zinc, known to be involved in improving immunity, may remodel some of the age-associated changes, leading to a healthy ageing. "In Vitro" studies involving human lymphocytes exposed to endotoxins, and "in vivo" studies comparing old and young mice fed with low dietary zinc suggest that zinc is important for both innate and adaptive immune efficiency, and more optimal inflammatory/immune response. The intracellular zinc homeostasis is mainly regulated by Metallothioneins (MT), via ion release through the reduction of thiol groups in MT molecule. These processes are crucial because mediating the zinc signalling within the immune cells assigning to zinc a role of "second messenger". Zinc homeostasis is altered in ageing partly due to higher expression levels of MT, leading to an increased sequestration of zinc, resulting in less availability of free intracellular zinc. Improvement of immune functions and stress response systems occurs in elderly after physiological zinc supplementation. The main reason behind these effects seems to be related to a like "hormetic" response induced by zinc. However, the choice of old subjects for zinc supplementation has to be performed in relationship to the specific genetic background of MT and pro-inflammatory cytokine (IL-6) because the latter is involved both in MT gene expression and in intracellular zinc homeostasis. Old subjects carrying GG genotypes (termed C- carriers) in IL-6--174G/C locus display increased IL-6 production, low intracellular zinc ion availability, impaired innate immune response and enhanced MT. By contrast, old subjects carrying GC and CC genotypes (termed C+ carriers) in the same IL-6--174 locus displayed satisfactory intracellular zinc and innate immune response. Moreover, male carriers of C+ allele are more prone to reach centenarian age than C- ones. Therefore, old C- subjects are likely to benefit more from zinc supplementation restoring NK cell cytotoxicity and improving the zinc status. Plasma zinc deficiency and the altered immune response is more evident when the genetic variations of IL-6 polymorphism are associated with the genetic variations of MT1A in position +647, suggesting that the genetic variations of IL-6 and MT1A are very useful tools for the identification of old people who effectively need zinc supplementation.

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“…Several studies on oxidative stress have been carried out in animal models, including the nematode Caenorhabditis elegans (Kahn et al 2008;Koon and Kubiseski 2010;Morimoto 2006), the fruit fly Drosophila Melanogaster (Ahamed et al 2010;Bahadorani et al 2010), and mice (Straadt et al 2010). C. elegans in particular exhibits defense mechanisms against oxidative stress similar to those in human beings, such as antioxidant enzymes, glutathione system, and stress response signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Inactivation of GABAA receptor is related to heat shock stress response in organism model Caenorhabditis elegans

Camargo

Elizalde

Trujillo

et al. 2016

Cell Stress and Chaperones

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The mechanisms underlying oxidative stress (OS) resistance are not completely clear. Caenorhabditis elegans (C. elegans) is a good organism model to study OS because it displays stress responses similar to those in mammals. Among these mechanisms, the insulin/IGF-1 signaling (IIS) pathway is thought to affect GABAergic neurotransmission. The aim of this study was to determine the influence of heat shock stress (HS) on GABAergic activity in C. elegans. For this purpose, we tested the effect of exposure to picrotoxin (PTX), gammaaminobutyric acid (GABA), hydrogen peroxide, and HS on the occurrence of a shrinking response (SR) after nose touch stimulus in N2 (WT) worms. Moreover, the effect of HS on the expression of UNC-49 (GABA A receptor ortholog) in the EG1653 strain and the effect of GABA and PTX exposure on HSP-16.2 expression in the TJ375 strain were analyzed. PTX 1 mM-or H 2 O 2 0.7 mM-exposed worms displayed a SR in about 80 % of trials. GABA exposure did not cause a SR. HS prompted the occurrence of a SR as did PTX 1 mM or H 2 O 2 0.7 mM exposure. In addition, HS increased UNC-49 expression, and PTX augmented HSP-16.2 expression. Thus, the results of the present study suggest that oxidative stress, through either H 2 O 2 exposure or application of heat shock, inactivates the GABAergic system, which subsequently would affect the oxidative stress response, perhaps by enhancing the activity of transcription factors DAF-16 and HSF-1, both regulated by the IIS pathway and related to hsp-16.2 expression.

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Overexpression of metal-responsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity

Cited by 45 publications

References 49 publications

A Drosophila model of Menkes disease reveals a role for DmATP7 in copper absorption and neurodevelopment

A Drosophila model of Menkes disease reveals a role for DmATP7 in copper absorption and neurodevelopment

Zinc, metallothioneins and immunosenescence: effect of zinc supply as nutrigenomic approach

Inactivation of GABAA receptor is related to heat shock stress response in organism model Caenorhabditis elegans

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