Arsenic binding proteins from human lymphoblastoid cells

Menzel, Daniel B.; Hamadeh, Hisham K.; Lee, Edward; Meacher, Dianne; Said, Victor; Rasmussen, Ronald E.; Greene, Howard L.; Roth, Randy Neal

doi:10.1016/s0378-4274(98)00380-4

Cited by 56 publications

(42 citation statements)

References 33 publications

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“…Cd (II) may also displace Zn and Ca ions from metalloproteins (Faller et al, 2005;Schutzendubel & Polle, 2002;Stohs & Bagchi, 1995) and zinc-finger proteins (Hartwig, 2001). As (III) has been shown to interact with TRR, pyruvate dehydrogenase and many other proteins (Kitchin & Wallace, 2008b;Menzel et al, 1999;Samikkannu et al, 2003;Wang et al, 2007). Besides, certain proteins may be more susceptible to As (III)-induced protein oxidation than to direct binding of As (III) to critical thiols (Samikkannu et al, 2003).…”

Section: Cadmium and Arsenate Toxicity The Role Of Oxidative Stressmentioning

confidence: 99%

The Yeast Genes ROX1, IXR1, SKY1 and Their Effect upon Enzymatic Activities Related to Oxidative Stress

Leiro¹,

Lombardero²,

Vázquez³

et al. 2012

Oxidative Stress - Molecular Mechanisms and Biological Effects

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Section: Cadmium and Arsenate Toxicity The Role Of Oxidative Stressmentioning

confidence: 99%

The Yeast Genes ROX1, IXR1, SKY1 and Their Effect upon Enzymatic Activities Related to Oxidative Stress

Leiro¹,

Lombardero²,

Vázquez³

et al. 2012

Oxidative Stress - Molecular Mechanisms and Biological Effects

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“…To prevent the accumulation of potentially toxic protein aggregates, cells utilize highly conserved defense mechanisms including molecular chaperones that facilitate disaggregation and reactivation of aggregated proteins, and the ubiquitin-proteasome pathway that contributes to aggregate removal through degradation (Buchberger et al, 2010;Goldberg, 2003;Liberek et al, 2008;Sharma et al, 2009). Trivalent arsenic [arsenite, As(OH) 3 or As(III)] has been shown to interact with several native proteins in mammalian cells, such as actin, tubulin and thioredoxin reductase, and the classical view is that enzyme inhibition is due to binding (Aposhian and Aposhian, 2006;Menzel et al, 1999;Zhang et al, 2007). As(III) disrupts the actin and tubulin cytoskeleton in budding yeast Saccharomyces cerevisiae (Pan et al, 2010;Thorsen et al, 2009), but whether this is caused by direct binding to actin and tubulin is not known.…”

Section: Introductionmentioning

confidence: 99%

Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast

Jacobson

Navarrete

Sharma

et al. 2012

Journal of Cell Science

132

225

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SummarySeveral metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.

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“…15,16 An affinity chromatographic approach was performed to isolate arsenic binding proteins from cells. 17 Only the molecular size and solubility of presumed arsenic binding proteins, however, could be derived from these studies, whereas almost nothing was learned about the bonding sites or mechanisms. In addition, the investigation of definite arsenic-phytochelatin complexes by means of different LC/MS methods revealed the strong influence of experimental conditions on the stability of such complexes.…”

mentioning

confidence: 99%

Mass spectrometric evidence for different complexes of peptides and proteins with arsenic(III), arsenic(V), copper(II), and zinc(II) species

Schmidt

Koppelt

Neustadt

et al. 2006

Rapid Comm Mass Spectrometry

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Trivalent and pentavalent arsenic were incubated with sulfur-containing amino acid, peptide and protein solutions both as organic compounds (phenylarsine oxide, phenylarsonic acid, dimethylarsinic acid, monomethylarsonic acid) and as inorganic compounds (arsenite, As(III), and arsenate, As(V)). After incubation of phenylarsine oxide solutions with cysteine and glutathione the mass spectra showed a covalent bond between arsenic and sulfur, which was stable at both acidic and neutral pH values. The mass spectra were dominated by monovalent ions at m/z 272 for cysteine samples and at m/z 458 for glutathione samples. Based on these masses the ionic structures could be ascribed to either fragment ions of the covalent arsenic-sulfur complexes or to other arsenic-bonding sites presumably at the amino group. Interestingly, under the same conditions no interactions of inorganic arsenite or arsenate could be measured. In the presence of added Cu(2+) ions all mass signals caused by a reaction of phenylarsine oxide with glutathione disappeared. In these mass spectra only the oxidised form of glutathione (GSSG) was found because of the redox activity of Cu(II). For the model protein lysozyme, no interactions with arsenic could be detected, whereas definite Cu- and Zn-lysozyme complexes with a stoichiometry of 1:1 and 2:1 for Zn(2+) ions and Cu(2+) ions, respectively, were observed. In contrast, for thioredoxin a bonding of As that depended on the concentration of the disulfide-reducing agent tris(2-carboxyethyl) phosphine was demonstrated. For three different phenylarsonic acids and for dimethylarsinic acid that all contain pentavalent arsenic, complexes with glutathione appeared in the mass spectra, which can be attributed to non-covalent interactions or to a covalent bond caused by an additive reaction. The optimisation of the experimental conditions necessary for the mass spectrometric analysis of the interactions of the arsenic species with peptides and proteins is described and the obtained mass spectra that provide information on the kinds of bonds are discussed.

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Arsenic binding proteins from human lymphoblastoid cells

Cited by 56 publications

References 33 publications

The Yeast Genes ROX1, IXR1, SKY1 and Their Effect upon Enzymatic Activities Related to Oxidative Stress

The Yeast Genes ROX1, IXR1, SKY1 and Their Effect upon Enzymatic Activities Related to Oxidative Stress

Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast

Mass spectrometric evidence for different complexes of peptides and proteins with arsenic(III), arsenic(V), copper(II), and zinc(II) species

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