Metallothioneins: new functional and structural insights

Vašák, Milan; Hasler, Daniel W.

doi:10.1016/s1367-5931(00)00082-x

Cited by 369 publications

(136 citation statements)

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“…So sequestering of free metal ions could avoid the formation of toxic ROS and alleviate the oxidative damage suffered by stressed plants. Antioxidative proteins, such as metallothionein, ceruloplasmin, and serum albumin, were indicated to control the generation of radicals by chelating metals (Kang et al 2001;Soriani et al 1994;Vasak & Hasler 2000). Therefore, plant dehydrins could also analogously prevent the production of ROS by sequestering metal ions, especially the catalytic metals.…”

Section: +mentioning

confidence: 99%

Role of plant dehydrins in antioxidation mechanisms

Sun

Lin

2010

Biologia

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Plant antioxidation system is composed of a series of complex mechanisms, in which many antioxidants including some special proteins are involved. Dehydrins are a family of late embryogenesis abundant (LEA) proteins which usually accumulate in plants during late embryogenesis or in response to environmental stresses. They were suggested to be associated with specific protective functions in plant cells, such as preventing coagulation of macromolecules and maintaining integrity of crucial cell structures. In recent years, many studies implied that dehydrins also play an antioxidative role to alleviate oxidative damage in stressed plants. They were proposed to scavenge radicals directly and sequester metals which are sources for radical generation to avoid the production of reactive oxygen species (ROS). In this paper, we will discuss the novel putative role of dehydrins in plant antioxidation mechanisms and how dehydrins perform their antioxidative activity.

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Section: +mentioning

confidence: 99%

Role of plant dehydrins in antioxidation mechanisms

Sun

Lin

2010

Biologia

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“…Typical responses of all eukaryotes to heavy metal load are the activation of transmembrane exporters, down-regulation of importers, complexation of heavy metals by conjugation to glutathione and last but not least, transcriptional induction of genes encoding heavy metal scavengers, notably metallothioneins (MTs) (Palmiter, 1998;DeMoor et al, 2000;Vasak and Hasler, 2000;Finney and O'Halloran, 2003;Urani et al, 2003). MTs are small, cysteine-rich proteins with the ability to complex heavy metals via their sulfhydryl groups.…”

Section: Introductionmentioning

confidence: 99%

Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison

Balamurugan

Egli²,

Selvaraj³

et al. 2004

Biological Chemistry

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The zinc finger transcription factor MTF-1 (metal-responsive transcription factor-1) is conserved from insects to vertebrates. Its major role in both organisms is to control the transcription of genes involved in the homeostasis and detoxification of heavy metal ions such as Cu 2q , Zn 2q and Cd 2q . In mammals, MTF-1 serves at least two additional roles. First, targeted disruption of the MTF-1 gene results in death at embryonic day 14 due to liver degeneration, revealing a stage-specific developmental role. Second, under hypoxic-anoxic stress, MTF-1 helps to activate the transcription of the gene placental growth factor (PlGF), an angiogenic protein. Recently we characterized dMTF-1, the Drosophila homolog of mammalian MTF-1. Here we present a series of studies to compare the metal response in mammals and insects, which reveal common features but also differences. A human MTF-1 transgene can restore to a large extent metal tolerance to flies lacking their own MTF-1 gene, both at low and high copper concentrations. Likewise, Drosophila MTF-1 can substitute for human MTF-1 in mammalian cell culture, although both the basal and the metal-induced transcript levels are lower. Finally, a clear difference was revealed in the response to mercury, a highly toxic heavy metal: metallothionein-type promoters respond poorly, if at all, to Hg 2q in mammalian cells but strongly in Drosophila, and this response is completely dependent on dMTF-1.

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“…Contrary to the peroxynitrite-induced activation of guanylyl cyclase, where GSH is needed, we found that the metal release from metallothionein by peroxynitrite is not enhanced, but also suppressed by reduced glutathione. In addition, we show that zinc, the major natural metal ligand in mammalian MTs and suppressor of iNOS, is released more readily under the influence of NO than cadmium, but in contrast to the MT isoform 1, the amount of metal released from the b-domain of MT-2 is comparable to that from the a-domain.Keywords: glutathione; metallothionein; nitric oxide; NMR spectroscopy; SEC-ICPMS.Metallothioneins (MTs) are a family of small (6-7 kDa) metal-binding proteins [1][2][3] with the highest known metal content after ferritins. The high amount of cysteine residues in MTs (30% of all amino acids are cysteine) allows these proteins to coordinate multiple mono (Cu + , Ag + ) or divalent metals (Zn 2+ , Cd 2+ ).…”

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confidence: 99%

Modulation of nitric oxide‐mediated metal release from metallothionein by the redox state of glutathione in vitro

Khatai

Goessler

Lorencova

et al. 2004

European Journal of Biochemistry

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Metallothioneins (MTs) release bound metals when exposed to nitric oxide. At inflammatory sites, both metallothionein and inducible nitric oxide synthase (iNOS) are induced by the same factors and the zinc released from metallothionein by NO suppresses both the induction and activity of iNOS. In a search for a possible modulatory mechanism of this coexpression of counteracting proteins, we investigated the role of the glutathione redox state in vitro because the oxidation state of thiols is involved in the metal binding in Cd-S or Zn-S clusters found in metallothioneins, and NO also binds to reduced glutathione via S-nitrosation. Using a variety of techniques, we found that NO and also ONOO --mediated metal release from purified MTs is suppressed by reduced glutathione (GSH), but not by oxidized glutathione. Considering the millimolar concentrations of GSH present in mammalian cells, the metal release from MTs by NO should play no role in living systems. Therefore, the fact that it has been observed in vivo points to a hitherto unknown mechanism or additional compound(s) being involved in this physiologically relevant reaction and as long as this additional factor is not found experimental results on the MT-NO interaction should be treated with caution. Contrary to the peroxynitrite-induced activation of guanylyl cyclase, where GSH is needed, we found that the metal release from metallothionein by peroxynitrite is not enhanced, but also suppressed by reduced glutathione. In addition, we show that zinc, the major natural metal ligand in mammalian MTs and suppressor of iNOS, is released more readily under the influence of NO than cadmium, but in contrast to the MT isoform 1, the amount of metal released from the b-domain of MT-2 is comparable to that from the a-domain.Keywords: glutathione; metallothionein; nitric oxide; NMR spectroscopy; SEC-ICPMS.Metallothioneins (MTs) are a family of small (6-7 kDa) metal-binding proteins [1][2][3] with the highest known metal content after ferritins. The high amount of cysteine residues in MTs (30% of all amino acids are cysteine) allows these proteins to coordinate multiple mono (Cu + , Ag + ) or divalent metals (Zn 2+ , Cd 2+ ). Mammalian MTs bind seven divalent metals in two separate domains [4]. Three metals are bound in an M 3 Cys 9 cluster in the N-terminal b-domain, while an M 4 Cys 11 four metal cluster is formed in the C-terminal a-domain [4]. Of the four known mammalian MT isoforms [2], the two best studied and most widely occurring isoforms (1 and 2) are most abundant in parenchymatous tissues, i.e. liver, kidney, pancreas and intestines [5][6][7] . The naturally bound metal zinc can be displaced by cadmium up to about 5 mol per mol protein by simple addition of Cd 2+ [13] in vitro. Living animals fed a cadmium-rich diet produce a mixed-metal MT with zinc bound preferentially in the b-and cadmium in the a-domain [11,13,14]. The artificial Cd 7 -MT can only be obtained after complete zinc removal by lowering the pH [15] in vitro.Although the biological function(s) o...

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Metallothioneins: new functional and structural insights

Cited by 369 publications

References 57 publications

Role of plant dehydrins in antioxidation mechanisms

Role of plant dehydrins in antioxidation mechanisms

Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison

Modulation of nitric oxide‐mediated metal release from metallothionein by the redox state of glutathione in vitro

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