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Special Issue "Metal Metabolism in Animals II"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioinorganic Chemistry".

Deadline for manuscript submissions: closed (18 June 2017).

Special Issue Editor

Guest Editor
Prof. Dr. Reinhard Dallinger Website E-Mail
Institute of Zoology, University of Innsbruck, Technikerstr. 25, 6020 Innsbruck, Austria
Interests: environmental toxicology and ecotoxicology; molecular physiology; microevolution of metal sensitivity; evolution, biochemistry and gene regulation of metallothioneins; metal-specific pathways in animal physiology; metal detoxification; metal-related biological indicators and biomarkers

Special Issue Information

Dear Colleagues,

The publication in this journal of the Special Issue on “Metal Metabolism in Animals” in 2015 was a great success, which can be accessed at https://www.mdpi.com/journal/ijms/special_issues/metal-metab-animal. It was instantly clear that this topic was quite diverse and complex. This is not only due to the physico-chemical variety of metals, many of them following distinct metabolic pathways or inducing specific pathological interactions within animal cells; in fact, many essential metallic trace elements serve—even at very low concentrations—as indispensable triggers of cellular regulatory processes, as they are constituents of enzymes, vitamins, and other bio-molecules. On the other hand, both essential and non-essential trace elements can exert toxic effects, if their intracellular concentrations exceed the limits of their specific tolerable range. Yet, we cannot be sure of the exact number of essential trace metals, so in the future it is possible that additional trace elements will have to be added to this number.

In the first issue of “Metal Metabolism in Animals”, topics such as metal tolerance and detoxification in non-model organisms, metal allergy, immunology and cytotoxicity, trace element homeostasis and interaction with metallo-enzymes, and the theoretical background of the biological role of metals in living systems were addressed. All these different subjects were discussed by a unified approach which was defined and circumscribed in a general manner as “metallomics” (see Dallinger 2015, introduction to the first issue of “Metal Metabolism in Animals” at https://www.mdpi.com/journal/ijms/special_issues/metal-metab-animal).

However, the editors feel that the first issue of “Metal Metabolism in Animals”, while having addressed a range of important topics, is far from exhaustive, and many subjects in this field were not touched upon. For example, the human dimension of trace element metabolism was not discussed, nor have the more ecologically oriented aspects of metal uptake and metabolism by animals exposed to metal-contaminated environments been sufficiently addressed. It was therefore decided to produce a second Special Issue of “Metal Metabolism in Animals”, in order to include so far neglected or less considered subjects in this field.

In particular, we welcome (in addition to the topics mentioned in the introduction of the first issue) topics such as the following:

  • Trace element uptake, regulation, and homeostasis in human nutrition;
  • All aspects of trace element deficiency in animals and humans;
  • Metal interaction with metallo-enzymes and their role in human and animal metabolism;
  • Metal interactions with vitamins and metabolic implications;
  • Metal ion availability in contaminated environments and its implication for metal accumulation and toxicological interactions in exposed animals;
  • Evolutionary, microevolutionary, and population-specific effects of metals on animal species in both the laboratory and in the wild;
  • Any other topic that focuses, in an integrative manner, on metal metabolism in animals, by addressing molecular and physiological aspects.

Prof. Dr. Reinhard Dallinger
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • Metal homeostasis
  • Metal toxicology
  • Metal deficiency
  • Metallo-enzymes and Metallo-proteins
  • Vitamins
  • Metal contamination and exposure

Related Special Issue

Published Papers (14 papers)

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Research

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Open AccessArticle
Successive Onset of Molecular, Cellular and Tissue-Specific Responses in Midgut Gland of Littorina littorea Exposed to Sub-Lethal Cadmium Concentrations
Int. J. Mol. Sci. 2017, 18(8), 1815; https://doi.org/10.3390/ijms18081815 - 22 Aug 2017
Cited by 8
Abstract
Cadmium (Cd) is one of the most harmful metals, being toxic to most animal species, including marine invertebrates. Among marine gastropods, the periwinkle (Littorina littorea) in particular can accumulate high amounts of Cd in its midgut gland. In this organ, the [...] Read more.
Cadmium (Cd) is one of the most harmful metals, being toxic to most animal species, including marine invertebrates. Among marine gastropods, the periwinkle (Littorina littorea) in particular can accumulate high amounts of Cd in its midgut gland. In this organ, the metal can elicit extensive cytological and tissue-specific alterations that may reach, depending on the intensity of Cd exposure, from reversible lesions to pathological cellular disruptions. At the same time, Littorina littorea expresses a Cd-specific metallothionein (MT) that, due to its molecular features, expectedly exerts a protective function against the adverse intracellular effects of this metal. The aim of the present study was, therefore, to assess the time course of MT induction in the periwinkle’s midgut gland on the one hand, and cellular and tissue-specific alterations in the digestive organ complex (midgut gland and digestive tract) on the other, upon exposure to sub-lethal Cd concentrations (0.25 and 1 mg Cd/L) over 21 days. Depending on the Cd concentrations applied, the beginning of alterations of the assessed parameters followed distinct concentration-dependent and time-dependent patterns, where the timeframe for the onset of the different response reactions became narrower at higher Cd concentrations compared to lower exposure concentrations. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessArticle
Challenging the Metallothionein (MT) Gene of Biomphalaria glabrata: Unexpected Response Patterns Due to Cadmium Exposure and Temperature Stress
Int. J. Mol. Sci. 2017, 18(8), 1747; https://doi.org/10.3390/ijms18081747 - 11 Aug 2017
Cited by 5
Abstract
Metallothioneins (MTs) are low-molecular-mass, cysteine-rich, metal binding proteins. In most animal species, they are involved in metal homeostasis and detoxification, and provide protection from oxidative stress. Gastropod MTs are highly diversified, exhibiting unique features and adaptations like metal specificity and multiplications of their [...] Read more.
Metallothioneins (MTs) are low-molecular-mass, cysteine-rich, metal binding proteins. In most animal species, they are involved in metal homeostasis and detoxification, and provide protection from oxidative stress. Gastropod MTs are highly diversified, exhibiting unique features and adaptations like metal specificity and multiplications of their metal binding domains. Here, we show that the MT gene of Biomphalaria glabrata, one of the largest MT genes identified so far, is composed in a unique way. The encoding for an MT protein has a three-domain structure and a C-terminal, Cys-rich extension. Using a bioinformatic approach involving structural and in silico analysis of putative transcription factor binding sites (TFBs), we found that this MT gene consists of five exons and four introns. It exhibits a regulatory promoter region containing three metal-responsive elements (MREs) and several TFBs with putative involvement in environmental stress response, and regulation of gene expression. Quantitative real-time polymerase chain reaction (qRT-PCR) data indicate that the MT gene is not inducible by cadmium (Cd) nor by temperature challenges (heat and cold), despite significant Cd uptake within the midgut gland and the high Cd tolerance of metal-exposed snails. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessArticle
Methylmercury Uptake into BeWo Cells Depends on LAT2-4F2hc, a System L Amino Acid Transporter
Int. J. Mol. Sci. 2017, 18(8), 1730; https://doi.org/10.3390/ijms18081730 - 08 Aug 2017
Cited by 4
Abstract
The organic mercury compound methylmercury (MeHg) is able to target the fetal brain. However, the uptake of the toxicant into placental cells is incompletely understood. MeHg strongly binds to thiol-S containing molecules such as cysteine. This MeHg-l-cysteine exhibits some structural similarity to methionine. [...] Read more.
The organic mercury compound methylmercury (MeHg) is able to target the fetal brain. However, the uptake of the toxicant into placental cells is incompletely understood. MeHg strongly binds to thiol-S containing molecules such as cysteine. This MeHg-l-cysteine exhibits some structural similarity to methionine. System L plays a crucial role in placental transport of essential amino acids such as leucine and methionine and thus has been assumed to also transport MeHg-l-cysteine across the placenta. The uptake of methylmercury and tritiated leucine and methionine into the choriocarcinoma cell line BeWo was examined using transwell assay and small interfering (si)RNA mediated gene knockdown. Upon the downregulation of large neutral amino acids transporter (LAT)2 and 4F2 cell-surface antigen heavy chain (4F2hc), respectively, the levels of [3H]leucine in BeWo cells are significantly reduced compared to controls treated with non-targeting siRNA (p < 0.05). The uptake of [3H]methionine was reduced upon LAT2 down-regulation as well as methylmercury uptake after 4F2hc silencing (p < 0.05, respectively). These findings suggest an important role of system L in the placental uptake of the metal. Comparing the cellular accumulation of mercury, leucine, and methionine, it can be assumed that (1) MeHg is transported through system L amino acid transporters and (2) system L is responsible for the uptake of amino acids and MeHg primarily at the apical membrane of the trophoblast. The findings together can explain why mercury in contrast to other heavy metals such as lead or cadmium is efficiently transported to fetal blood. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessArticle
The Construction and Characterization of Mitochondrial Ferritin Overexpressing Mice
Int. J. Mol. Sci. 2017, 18(7), 1518; https://doi.org/10.3390/ijms18071518 - 13 Jul 2017
Cited by 2
Abstract
Mitochondrial ferritin (FtMt) is a H-ferritin-like protein which localizes to mitochondria. Previous studies have shown that this protein can protect mitochondria from iron-induced oxidative damage, while FtMt overexpression in cultured cells decreases cytosolic iron availability and protects against oxidative damage. To investigate the [...] Read more.
Mitochondrial ferritin (FtMt) is a H-ferritin-like protein which localizes to mitochondria. Previous studies have shown that this protein can protect mitochondria from iron-induced oxidative damage, while FtMt overexpression in cultured cells decreases cytosolic iron availability and protects against oxidative damage. To investigate the in vivo role of FtMt, we established FtMt overexpressing mice by pro-nucleus microinjection and examined the characteristics of the animals. We first confirmed that the protein levels of FtMt in the transgenic mice were increased compared to wild-type mice. Interestingly, we found no significant differences in the body weights or organ to body weight ratios between wild type and transgenic mice. To determine the effects of FtMt overexpression on baseline murine iron metabolism and hematological indices, we measured serum, heart, liver, spleen, kidney, testis, and brain iron concentrations, liver hepcidin expression and red blood cell parameters. There were no significant differences between wild type and transgenic mice. In conclusion, our results suggest that FtMt overexpressing mice have no significant defects and the overexpression of FtMt does not affect the regulation of iron metabolism significantly in transgenic mice. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessArticle
Effects of Protein-Iron Complex Concentrate Supplementation on Iron Metabolism, Oxidative and Immune Status in Preweaning Calves
Int. J. Mol. Sci. 2017, 18(7), 1501; https://doi.org/10.3390/ijms18071501 - 12 Jul 2017
Cited by 2
Abstract
The objective of this study was to determine the effects of feeding protein-iron complex (PIC) on productive performance and indicators of iron metabolism, hematology parameters, antioxidant and immune status during first 35 days of a calf’s life. Preparation of the complex involved enzymatic [...] Read more.
The objective of this study was to determine the effects of feeding protein-iron complex (PIC) on productive performance and indicators of iron metabolism, hematology parameters, antioxidant and immune status during first 35 days of a calf’s life. Preparation of the complex involved enzymatic hydrolysis of milk casein (serine protease from Yarrowia lipolytica yeast). Iron chloride was then added to the hydrolyzate and lyophilizate. Calves were divided into treated groups: LFe (low iron dose) 10 g/day calf of protein-iron complex, HFe (height iron dose) 20 g/day calf, and control group. Dietary supplements containing the lower dose of concentrate had a significant positive effect on iron metabolism, while the higher dose of concentrate resulted in increase of total iron binding capacity (TIBC), saturation of transferrin and decrease of and unsaturated iron binding capacity (UIBC), which suggest iron overload. Additionally, treatment with the lower dose of iron remarkably increased the antioxidant parameters, mainly total antioxidant (TAS) and glutathione peroxidase activity (GPx). Higher doses of PIC were related to lower total antioxidant status. IgG, IgM, insulin, glucose, TNFα and IGF-1 concentration did not change significantly in either group after supplementation. In practice, the use of protein-iron complex concentrate requires taking into account the iron content in milk replacers and other feedstuffs. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessArticle
Fexofenadine Suppresses Delayed-Type Hypersensitivity in the Murine Model of Palladium Allergy
Int. J. Mol. Sci. 2017, 18(7), 1357; https://doi.org/10.3390/ijms18071357 - 25 Jun 2017
Cited by 2
Abstract
Palladium is frequently used in dental materials, and sometimes causes metal allergy. It has been suggested that the immune response by palladium-specific T cells may be responsible for the pathogenesis of delayed-type hypersensitivity in study of palladium allergic model mice. In the clinical [...] Read more.
Palladium is frequently used in dental materials, and sometimes causes metal allergy. It has been suggested that the immune response by palladium-specific T cells may be responsible for the pathogenesis of delayed-type hypersensitivity in study of palladium allergic model mice. In the clinical setting, glucocorticoids and antihistamine drugs are commonly used for treatment of contact dermatitis. However, the precise mechanism of immune suppression in palladium allergy remains unknown. We investigated inhibition of the immune response in palladium allergic mice by administration of prednisolone as a glucocorticoid and fexofenadine hydrochloride as an antihistamine. Compared with glucocorticoids, fexofenadine hydrochloride significantly suppressed the number of T cells by interfering with the development of antigen-presenting cells from the sensitization phase. Our results suggest that antihistamine has a beneficial effect on the treatment of palladium allergy compared to glucocorticoids. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessArticle
TRAV7-2*02 Expressing CD8+ T Cells Are Responsible for Palladium Allergy
Int. J. Mol. Sci. 2017, 18(6), 1162; https://doi.org/10.3390/ijms18061162 - 31 May 2017
Cited by 2
Abstract
While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T [...] Read more.
While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T cell subsets and the specific T cell receptor (TCR) have not been identified. Therefore, we attempted to identify the pathogenic T cells responsible for Pd allergy. We found that activating CD8+ T cells significantly increased and that the TRAV (TCRα variable) 7-2*02 chain skewed in Pd allergic mice. Furthermore, adoptive transfer experiments revealed that in vitro-cultured Pd-stimulated antigen presenting cells (APCs) function as memory APCs with recipient mice developing Pd allergy and that the frequency of TRAV7-2*02 increases the same as conventional Pd allergic mice. In contrast, neither proliferation of CD8+ T cells nor increasing of TRAV7-2*02 was observed in major histocompatibility complex I (MHC I)-deficient Pd-APCs transferred to mice. Taken together, we revealed that TRAV7-2*02-expressing CD8+ T cells are the pathogenic T cells for the development of Pd allergy. We also identified the CDR3 consensus motif of pathogenic TCRs as CAAXSGSWQLIF in TRAV7-2*02/TRAJ (TCRα junction)22*01 positive cells. These results suggest that the specific TCRs represent novel targets for the development of diagnostics and treatments for metal allergy. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessArticle
Administration of Zinc plus Cyclo-(His-Pro) Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes
Int. J. Mol. Sci. 2017, 18(1), 73; https://doi.org/10.3390/ijms18010073 - 01 Jan 2017
Cited by 3
Abstract
The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro) (ZC) on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ)-induced diabetes. ZC (27 mg/kg) was [...] Read more.
The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro) (ZC) on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ)-induced diabetes. ZC (27 mg/kg) was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase) or 45 (late phase) days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs) and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Review

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Open AccessReview
Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma
Int. J. Mol. Sci. 2017, 18(8), 1718; https://doi.org/10.3390/ijms18081718 - 07 Aug 2017
Cited by 8
Abstract
Recent data have indicated a fundamental role of iron in mediating a non-apoptotic and non-necrotic oxidative form of programmed cell death termed ferroptosis that requires abundant cytosolic free labile iron to promote membrane lipid peroxidation. Different scavenger molecules and detoxifying enzymes, such as [...] Read more.
Recent data have indicated a fundamental role of iron in mediating a non-apoptotic and non-necrotic oxidative form of programmed cell death termed ferroptosis that requires abundant cytosolic free labile iron to promote membrane lipid peroxidation. Different scavenger molecules and detoxifying enzymes, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), have been shown to overwhelm or exacerbate ferroptosis depending on their expression magnitude. Ferroptosis is emerging as a potential weapon against tumor growth since it has been shown to potentiate cell death in some malignancies. However, this mechanism has been poorly studied in Rhabdomyosarcoma (RMS), a myogenic tumor affecting childhood and adolescence. One of the main drivers of RMS genesis is the Retrovirus Associated DNA Sequences/Extracellular signal Regulated Kinases (RAS/ERK)signaling pathway, the deliberate activation of which correlates with tumor aggressiveness and oxidative stress levels. Since recent studies have indicated that treatment with oxidative inducers can significantly halt RMS tumor progression, in this review we covered different aspects, ranging from iron metabolism in carcinogenesis and tumor growth, to mechanisms of iron-mediated cell death, to highlight the potential role of ferroptosis in counteracting RMS growth. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessReview
Cadmium Handling, Toxicity and Molecular Targets Involved during Pregnancy: Lessons from Experimental Models
Int. J. Mol. Sci. 2017, 18(7), 1590; https://doi.org/10.3390/ijms18071590 - 22 Jul 2017
Cited by 11
Abstract
Even decades after the discovery of Cadmium (Cd) toxicity, research on this heavy metal is still a hot topic in scientific literature: as we wrote this review, more than 1440 scientific articles had been published and listed by the PubMed.gov website during 2017. [...] Read more.
Even decades after the discovery of Cadmium (Cd) toxicity, research on this heavy metal is still a hot topic in scientific literature: as we wrote this review, more than 1440 scientific articles had been published and listed by the PubMed.gov website during 2017. Cadmium is one of the most common and harmful heavy metals present in our environment. Since pregnancy is a very particular physiological condition that could impact and modify essential pathways involved in the handling of Cd, the prenatal life is a critical stage for exposure to this non-essential element. To give the reader an overview of the possible mechanisms involved in the multiple organ toxic effects in fetuses after the exposure to Cd during pregnancy, we decided to compile some of the most relevant experimental studies performed in experimental models and to summarize the advances in this field such as the Cd distribution and the factors that could alter it (diet, binding-proteins and membrane transporters), the Cd-induced toxicity in dams (preeclampsia, fertility, kidney injury, alteration in essential element homeostasis and bone mineralization), in placenta and in fetus (teratogenicity, central nervous system, liver and kidney). Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessReview
Unravelling the Role of Metallothionein on Development, Reproduction and Detoxification in the Wall Lizard Podarcis sicula
Int. J. Mol. Sci. 2017, 18(7), 1569; https://doi.org/10.3390/ijms18071569 - 19 Jul 2017
Cited by 1
Abstract
Metallothioneins (MTs) are an evolutionary conserved multigene family of proteins whose role was initially identified in binding essential metals. The physiological role of MT, however, has been revealed to be more complex than expected, since not only are MTs able to bind to [...] Read more.
Metallothioneins (MTs) are an evolutionary conserved multigene family of proteins whose role was initially identified in binding essential metals. The physiological role of MT, however, has been revealed to be more complex than expected, since not only are MTs able to bind to toxic heavy metals, but many isoforms have shown specialized and alternative functions. Within this uncertainty, the information available on MTs in non-mammalian vertebrates, particularly in neglected tetrapods such as the reptiles, is even more scant. In this review, we provide a summary of the current understanding on metallothionein presence and function in the oviparous lizard Podarcis sicula, highlighting the results obtained by studying MT gene expression in most representative adult and embryonic tissues. The results demonstrate that in adults, cadmium induces MT transcription in a dose- and tissue-specific manner. Thus, the MT mRNAs appear, at least in some cases, to be an unsuitable tool for detecting environmental ion contamination. In early embryos, maternal RNAs sustain developmental needs for MT protein until organogenesis is well on its way. At this time, transcription starts, but again in a tissue- and organ-specific manner, suggesting an involvement in alternative roles. In conclusion, the spatiotemporal distribution of transcripts in adults and embryos definitively confirms that MT has deserved the title of elusive protein. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessReview
Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity
Int. J. Mol. Sci. 2017, 18(7), 1456; https://doi.org/10.3390/ijms18071456 - 06 Jul 2017
Cited by 13
Abstract
Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its [...] Read more.
Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its deficiency, excess or misplacement. Interestingly, the main components of metal homeostatic pathways are conserved, with many orthologues of the human metal-related genes having been identified and characterized in Drosophila melanogaster. Drosophila has gained appreciation as a useful model for studying human diseases, including those caused by mutations in pathways controlling cellular metal homeostasis. Flies have many advantages in the laboratory, such as a short life cycle, easy handling and inexpensive maintenance. Furthermore, they can be raised in a large number. In addition, flies are greatly appreciated because they offer a considerable number of genetic tools to address some of the unresolved questions concerning disease pathology, which in turn could contribute to our understanding of the metal metabolism and homeostasis. This review recapitulates the metabolism of the principal transition metals, namely iron, zinc and copper, in Drosophila and the utility of this organism as an experimental model to explore the role of metal dyshomeostasis in different human diseases. Finally, a summary of the contribution of Drosophila as a model for testing metal toxicity is provided. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessReview
Roles of Copper-Binding Proteins in Breast Cancer
Int. J. Mol. Sci. 2017, 18(4), 871; https://doi.org/10.3390/ijms18040871 - 20 Apr 2017
Cited by 9
Abstract
Copper ions are needed in several steps of cancer progression. However, the underlying mechanisms, and involved copper-binding proteins, are mainly elusive. Since most copper ions in the body (in and outside cells) are protein-bound, it is important to investigate what copper-binding proteins participate [...] Read more.
Copper ions are needed in several steps of cancer progression. However, the underlying mechanisms, and involved copper-binding proteins, are mainly elusive. Since most copper ions in the body (in and outside cells) are protein-bound, it is important to investigate what copper-binding proteins participate and, for these, how they are loaded with copper by copper transport proteins. Mechanistic information for how some copper-binding proteins, such as extracellular lysyl oxidase (LOX), play roles in cancer have been elucidated but there is still much to learn from a biophysical molecular viewpoint. Here we provide a summary of copper-binding proteins and discuss ones reported to have roles in cancer. We specifically focus on how copper-binding proteins such as mediator of cell motility 1 (MEMO1), LOX, LOX-like proteins, and secreted protein acidic and rich in cysteine (SPARC) modulate breast cancer from molecular and clinical aspects. Because of the importance of copper for invasion/migration processes, which are key components of cancer metastasis, further insights into the actions of copper-binding proteins may provide new targets to combat cancer. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessReview
Anemia in Kawasaki Disease: Hepcidin as a Potential Biomarker
Int. J. Mol. Sci. 2017, 18(4), 820; https://doi.org/10.3390/ijms18040820 - 12 Apr 2017
Cited by 7
Abstract
Kawasaki disease (KD) is an autoimmune-like disease and acute childhood vasculitis syndrome that affects various systems but has unknown etiology. In addition to the standard diagnostic criteria, anemia is among the most common clinical features of KD patients and is thought to have [...] Read more.
Kawasaki disease (KD) is an autoimmune-like disease and acute childhood vasculitis syndrome that affects various systems but has unknown etiology. In addition to the standard diagnostic criteria, anemia is among the most common clinical features of KD patients and is thought to have a more prolonged duration of active inflammation. In 2001, the discovery of a liver-derived peptide hormone known as hepcidin began revolutionizing our understanding of anemia’s relation to a number of inflammatory diseases, including KD. This review focuses on hepcidin-induced iron deficiency’s relation to transient hyposideremia, anemia, and disease outcomes in KD patients, and goes on to suggest possible routes of further study. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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