Systematic functional characterization of putative zinc transport genes and identification of zinc toxicosis phenotypes in<i>Drosophila melanogaster</i>

Lye, Jessica; Richards, Christopher D.; Dechen, Kesang; Paterson, David; Jonge, Martin D. de; Howard, Daryl L.; Warr, Coral G.; Burke, Richard

doi:10.1242/jeb.069260

Cited by 49 publications

(77 citation statements)

References 57 publications

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“…This is what we observed when we used ZIP42C1, closely related to mammalian ZIP1-3 (SLC39A1-3), and ZIP71B, very related to mammalian ZIP5 and ZIP6 (SLC39A5 and SLC39A6) and Foi (Lye et al, 2012), in our rescue experiments. Furthermore, this interpretation was reinforced by the worsening of phenotypes when we attempted rescuing the absence of Foi with ZnT1.…”

Section: Discussionsupporting

confidence: 82%

“…This is in striking contrast with the cellular control of copper homeostasis, which is accomplished by only four transporters (Gupta and Lutsenko, 2009), and therefore raises the question of why there is a need for so many transporters. Data obtained from knockout mice for various ZIP and ZnT members (reviewed by Chasapis et al, 2012) and from a functional analysis of all the zinc transporters in Drosophila (Lye et al, 2012(Lye et al, , 2013 have revealed that there are specific requirements for several zinc transporters and that this specificity relies, at least in part, on the patterns of expression of their encoding genes and on their subcellular localization. Interestingly, the function of some transporters is conserved across species (Wang et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, 17 Drosophila genes encoding proteins with sequence homology to mammalian ZIP and ZnT families of zinc transporters have been identified and the proposed functions for several of them as transporters involved in zinc uptake or export have been validated (Lye et al, 2012(Lye et al, , 2013. For our rescue experiments, we chose to use Catecholamines up (Catsup) as a representative of a ZIP transporter with organelle localization, ZnT1 (ZnT63C -FlyBase) as a ZnT transporter localized to the apical and basolateral plasma membranes, and ZIP42C.1 (encoded by CG9428) and ZIP71B (encoded by CG10006) as ZIP transporters localized both intracellularly and at the basolateral membrane (Lye et al, 2013).…”

Section: The Function Of Foi As a Zinc Transporter Mediates Its Role mentioning

confidence: 99%

“…Indeed, there are a large number of genes belonging to the ZIP and ZnT families encoded in mammalian and Drosophila genomes. Recently, functional analyses measuring the phenotypic effects of zinc toxicity in the fly have demonstrated that most of the 17 putative zinc transporters of Drosophila work as such and suggest that several of them could be acting together in the same tissue (Lye et al, 2012). However, in spite of the implication that several mammalian and Drosophila zinc transporters have roles in sustaining proper development and preventing disease, little is known about how they actually work at the cellular level and to what an extent they can substitute for each other.…”

Section: Introductionmentioning

confidence: 99%

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Fear-of-intimacy mediated zinc transport controls the function of Zn-finger transcription factors involved in myogenesis

et al. 2016

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Zinc is a component of one-tenth of all human proteins. Its cellular concentration is tightly regulated because its dyshomeostasis has catastrophic health consequences. Two families of zinc transporters control zinc homeostasis in organisms, but there is little information about their specific developmental roles. We show that the ZIP transporter Fear-of-intimacy (Foi) is necessary for the formation of Drosophila muscles. In foi mutants, myoblasts segregate normally, but their specification is affected, leading to the formation of a misshapen muscle pattern and distorted midgut. The observed phenotypes could be ascribed to the inactivation of specific zincfinger transcription factors (ZFTFs), supporting the hypothesis that they are a consequence of intracellular depletion of zinc. Accordingly, foi phenotypes can be rescued by mesodermal expression of other ZIP members with similar subcellular localization. We propose that Foi acts mostly as a transporter to regulate zinc intracellular homeostasis, thereby impacting on the activity of ZFTFs that control specific developmental processes. Our results additionally suggest a possible explanation for the presence of large numbers of zinc transporters in organisms based on differences in ion transport specificity and/or degrees of activity among transporters.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: The Function Of Foi As a Zinc Transporter Mediates Its Role mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fear-of-intimacy mediated zinc transport controls the function of Zn-finger transcription factors involved in myogenesis

et al. 2016

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“…5 On top of its great chemical sensing and electric conductivity, ZnO NPs possess ultraviolet scattering and antimicrobial (both antibacterial and antifungal) properties. Their bactericidal values are useful for biomedical applications and food packaging.…”

Section: Introductionmentioning

confidence: 99%

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and <em>Drosophila melanogaster</em>

Yong

Hande³

et al. 2017

IJN

199

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Background Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient. Methods In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster . A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs. Results For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript ( DDIT3 ) and endoplasmic reticulum (ER) to nucleus signaling 1 ( ERN1 ) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production. Conclusion The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in vivo. More extensive studies would be needed to verify the safety issues related to increased usage of ZnO NPs by consumers.

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Green‐synthesized Zinc oxide nanoparticle, an efficient safe anticancer compound for human breast MCF7 cancer cells

Salari

Neamati

Tabrizi

et al. 2019

Applied Organom Chemis

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There are many types of researches investigating anticancer therapeutics for breast cancer therapy. Zinc oxide nanoparticles (ZnONPs) as an efficient drug delivery system, has been widely being used in various biomedical applications. In the current study, we synthesized ZnONP applying Rheum rhaponticum Waste (RRW) as a novel bio‐platform to investigate its anticancer impacts on MCF7 breast cancer cells compared with normal Human HFF and HDF cells. In this regard, RRW was triggered to synthesize the ZnONPs. Then, they were characterized by XRD, FTIR, TEM, and SEM analysis. Next, the MCF‐7, HFF, and HDF cell lines were cultured and treated as the following plane: Incubation of all cell lines for 72, 48, and 24 hours at the presence of different ZnONPs doses. Finally, the cell morphology, BCL2‐ BAX genes expression profile and AO/PI‐fluorescent cell staining on the 48‐hour incubated cells were analyzed to check the ZnONP apoptotic activity. Moreover, the ZnONP antioxidant activity was analyzed by a DPPH antioxidant test. We produced the 30 nm ZnONPs which significantly increased the BAX and decreased the BCL‐2 gene expression. According to the results including the Sub G1 enhancement peaks, apoptotic hallmarks, MTT assay, and the AO/PI‐fluorescent stained cells, ZnONPs can specifically induce apoptotic death in MCF7 breast cancer cells compared with normal HFF and HDF cells. The IC50 values of MCF‐7 in 72, 48, and 24 hr were measured at 8, 11, and 12 μg/ml in 72, 48, and 24 hr, respectively. This is while the mentioned values in the normal cells (HFF, HDF) were estimated at higher treatment doses. In conclusion, we suggest that the ZnONPs have the potential to be applied as a safe cell‐specific apoptosis inducer in breast cancer treatment. However, there are many challenges that need to be clarified for applying them as an efficient anticancer agent.

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Systematic functional characterization of putative zinc transport genes and identification of zinc toxicosis phenotypes inDrosophila melanogaster

Cited by 49 publications

References 57 publications

Fear-of-intimacy mediated zinc transport controls the function of Zn-finger transcription factors involved in myogenesis

Fear-of-intimacy mediated zinc transport controls the function of Zn-finger transcription factors involved in myogenesis

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and <em>Drosophila melanogaster</em>

Green‐synthesized Zinc oxide nanoparticle, an efficient safe anticancer compound for human breast MCF7 cancer cells

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