Arsenic Interaction with Zinc Finger Motifs

Hudson, Laurie G.; Cooper, Karen L.; Atlas, Susan R.; King, Brenee; Liu, Ke Jian

doi:10.1002/9781118876992.ch13

Cited by 3 publications

(5 citation statements)

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“…Our findings indicate that uranium is capable of disrupting zinc finger DNA repair proteins similar to what has been reported for other carcinogenic and co-carcinogenic metals such as arsenic (Beyersmann and Hartwig, 2008; Ding et al, 2009; Bal et al, 2011; Zhou et al, 2011; Hartwig, 2013; Sun et al, 2014; Zhou et al, 2014; Hudson et al, 2015). Past work on interactions of uranium with zinc finger proteins is limited, but proteomics analysis of uranium-interacting proteins identified PARP-1 (Dedieu et al, 2009), and uranium inhibits DNA binding of certain transcription factors including the C2H2 zinc finger proteins Sp1 and Aart (Hartsock et al, 2007).…”

Section: Discussionsupporting

confidence: 85%

“…3D). Xeroderma Pigmentosum, Complementation Group A (XPA) has a single C4 zinc finger that is sensitive to other carcinogenic metals such as arsenic (Piatek et al, 2008; Zhou et al, 2011; Hudson et al, 2015) and zinc content of XPA was reduced after treatment with UA. UA was previously reported to interfere with the DNA binding capacity of the C 2 H 2 zinc finger protein specificity protein 1 (Sp1) (Hartsock et al, 2007) and UA treatment caused zinc loss from this protein as well as another C2H2 zinc finger protein, aprataxin (APTX).…”

Section: Resultsmentioning

confidence: 99%

“…Proteins with zinc-finger structures are the most abundant class of zinc metalloproteins, representing an estimated 2–3% of human genes whose protein products regulate diverse functions in cells (Maret, 2012; Hudson et al, 2015). Certain metals can interact with zinc finger structures of proteins and thereby disrupt protein function (Witkiewicz-Kucharczyk and Bal, 2006; Beyersmann and Hartwig, 2008; Ding et al, 2009; Bal et al, 2011; Zhou et al, 2011; Hartwig, 2013; Sun et al, 2014; Zhou et al, 2014; Hudson et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Certain metals can interact with zinc finger structures of proteins and thereby disrupt protein function (Witkiewicz-Kucharczyk and Bal, 2006; Beyersmann and Hartwig, 2008; Ding et al, 2009; Bal et al, 2011; Zhou et al, 2011; Hartwig, 2013; Sun et al, 2014; Zhou et al, 2014; Hudson et al, 2015). Metal inhibition of proteins involved in DNA repair has led to the hypothesis that low concentrations of certain metals may serve as co-carcinogens by preventing effective repair of DNA damage caused by another insult.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

Cooper

Dashner

Tsosie

et al. 2016

Toxicology and Applied Pharmacology

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Uranium has radiological and non-radiological effects within biological systems and there is increasing evidence for genotoxic and carcinogenic properties attributable to uranium through its heavy metal properties. In this study, we report that low concentrations of uranium (as uranyl acetate; <10 μM) is not cytotoxic to human embryonic kidney cells or normal human keratinocytes; however, uranium exacerbates DNA damage and cytotoxicity induced by hydrogen peroxide, suggesting that uranium may inhibit DNA repair processes. Concentrations of uranyl acetate in the low micromolar range inhibited the zinc finger DNA repair protein poly(ADP-ribose) polymerase (PARP)-1 and caused zinc loss from PARP-1 protein. Uranyl acetate exposure also led to zinc loss from the zinc finger DNA repair proteins Xeroderma Pigmentosum, Complementation Group A (XPA) and aprataxin (APTX). In keeping with the observed inhibition of zinc finger function of DNA repair proteins, exposure to uranyl acetate enhanced retention of induced DNA damage. Co-incubation of uranyl acetate with zinc largely overcame the impact of uranium on PARP-1 activity and DNA damage. These findings present evidence that low concentrations of uranium can inhibit DNA repair through disruption of zinc finger domains of specific target DNA repair proteins. This may provide a mechanistic basis to account for the published observations that uranium exposure is associated with DNA repair deficiency in exposed human populations.

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Section: Discussionsupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

Cooper

Dashner

Tsosie

et al. 2016

Toxicology and Applied Pharmacology

Self Cite

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“…The mechanisms underlying the noted associations of As with Ca, Cu, Fe and Zn in the brains and livers of bears and wolves are not well understood and may well have origins in the As affinity to protein sulfhydryls containing the mentioned essential elements [ 9 , 84 ]. Arsenic was proven to interact with certain Zn finger motifs and to disrupt this essential protein [ 84 , 85 ]. Cadmium and Ca were highly correlated in wolf brains, which is consistent with the described mechanism of Cd-related neurotoxicity based on ion mimicry involving competition with Ca ions and impairment of Ca levels, an important secondary messenger in the brain [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Lead and Other Trace Element Levels in Brains of Croatian Large Terrestrial Carnivores: Influence of Biological and Ecological Factors

Lazarus

Sekovanić²,

Reljić³

et al. 2022

Toxics

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Trace element pollution can adversely affect the brains of individuals and thus impact the entire population of apex predators, such as large European carnivores. We assessed exposure to prominent neurotoxicants As, Cd, Hg and Pb by measuring their brain stem levels in brown bears (n = 114), grey wolves (n = 8), Eurasian lynx (n = 3), and golden jackals (n = 2) sampled in 2015–2022 in Croatia. The highest of the non-essential elements was the Pb level in the bearsʼ brains (median, Q1-Q3; 11.1, 7.13–24.1 μg/kg wet mass), with 4% of animals, all subadults, exceeding the established normal bovine levels (100 μg/kg wet mass). Species-specific differences were noted for Ca, Cd, Cu, Fe, Pb and Se brain levels. Female brown bears had higher As brain levels than males. Cubs and yearlings had lower brain Cd, but higher Zn, while subadults had higher Cu than adult bears. Hepatic As, Cd, Cu and Hg levels were shown to be a moderate proxy for estimating brain levels in bears (rS = 0.30–0.69). Multiple associations of As, Cd, Hg and Pb with essential elements pointed to a possible interaction and disturbance of brain Ca, Cu, Fe, Se and Zn homeostasis. Non-essential element levels in the brains of four studied species were lower than reported earlier for terrestrial meso-carnivores and humans. The age and sex of animals were highlighted as essential factors in interpreting brain element levels in ecotoxicological studies of large carnivores.

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Mining and Environmental Health Disparities in Native American Communities

Lewis

Hoover

MacKenzie

2017

Curr Envir Health Rpt

127

113

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Purpose of ReviewMore than a century of hard rock mining has left a legacy of >160,000 abandoned mines in the Western USA that are home to the majority of Native American lands. This article describes how abrogation of treaty rights, ineffective policies, lack of infrastructure, and a lack of research in Native communities converge to create chronic exposure, ill-defined risks, and tribal health concerns.Recent FindingsRecent results show that Native Americans living near abandoned uranium mines have an increased likelihood for kidney disease and hypertension, and an increased likelihood of developing multiple chronic diseases linked to their proximity to the mine waste and activities bringing them in contact with the waste. Biomonitoring confirms higher than expected exposure to uranium and associated metals in the waste in adults, neonates, and children in these communities.SummaryThese sites will not be cleaned up for many generations making it critical to understand and prioritize exposure-toxicity relationships in Native populations to appropriately allocate limited resources to protect health. Recent initiatives, in partnership with Native communities, recognize these needs and support development of tribal research capacity to ensure that research respectful of tribal culture and policies can address concerns in the future. In addition, recognition of the risks posed by these abandoned sites should inform policy change to protect community health in the future.

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Arsenic Interaction with Zinc Finger Motifs

Cited by 3 publications

References 132 publications

Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

Lead and Other Trace Element Levels in Brains of Croatian Large Terrestrial Carnivores: Influence of Biological and Ecological Factors

Mining and Environmental Health Disparities in Native American Communities

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