Arsenite inhibits two steps in the ubiquitin-dependent proteolytic pathway

Klemperer, Nancy; Pickart, Cecile M.

doi:10.1016/s0021-9258(19)47293-1

Cited by 66 publications

(14 citation statements)

References 39 publications

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“…Indeed, others have already suggested a role for cytosolic hsp 70 in the presentation of certain proteins to the lysosome for their subsequent degradation (Chiang et al, 1989). In the case of sodium arsenite, we suspect it perturbs the folding of newly synthesized proteins via its ability to interact with free thiol groups (Zahler and Cleland, 1968;Klemperer and Pickart, 1989). Support for this idea was our observation that addition of the reducing agent, DTT, was sufficient to reverse the adverse effects of arsenite on protein maturation.…”

Section: Discussionmentioning

confidence: 55%

“…Why then are newly synthesized proteins made in the presence of sodium arsenite not released from hsp 72/73? Previous studies have shown that arsenite inactivates various enzymes via binding to vicinal cysteine residues and that such inactivation can be reversed via the addition of the reducing agent, DTT (Zahler and Cleland, 1968;Klemperer and Pickart, 1989). Consequently, we suspected that arsenite might result in the cross-linking of cysteine residues within the nascent polypeptide chain, and thereby prevent proper folding.…”

Section: The Adverse Effects Of Sodium Arsenite On Protein Maturation Can Be Reversed Via Addition Of the Reducing Agent Dttmentioning

confidence: 97%

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Examining the function and regulation of hsp 70 in cells subjected to metabolic stress

Beckmann

Lovett

Welch

1992

The Journal of Cell Biology

233

112

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Abstract. Members of the heat-shock protein fhsp) 70 family, distributed within various cellular compartments, have been implicated in facilitating protein maturation events. In particular, related hsp 70 family members appear to bind nascent polypeptides which are in the course of synthesis and/or translocation into organelles. We previously reported that in normal, unstressed cells, cytosolic hsp 70 (hsp 72/73) interacted transiently with nascent polypeptides. We suspect that such interactions function to prevent or slow down the folding of the nascent polypeptide chain. Once synthesis is complete, and now with all of the information for folding present, the newly synthesized protein appears to commence along its folding pathway, aocompartied by the ATP-dependent release of hsp 72/73. Herein, we examined how these events occur in cells subjected to different types of metabolic stress. In cells exposed to either an amino acid analog or sodium arsenite, two potent inducers of the stress response, newly synthesized proteins bind to but are not released from hsp 70. Under these conditions of metabolic stress, we suspect that the newly synthesized proteins are unable to commence proper folding and consequently remain bound to their hsp 70 chaperone. In cells subjected to heat shock, a large number of both newly synthesized as well as mature proteins are rendered insoluble. Within this insoluble material are appreciable amounts of hsp 72/73. Finally, we show that in cells depleted of ATE the release of hsp 70 from maturing proteins is inhibited. Thus, in cells experiencing metabolic stress, newly synthesized proteins unable to properly fold, as will as mature proteins which begin to unfold become stably bound to hsp 72/73. As a consequence and over time, the free or available levels of pre-existing hsp 72/73 are reduced. We propose that this reduction in the available levels of hsp 72/73 is the trigger by which the stress response is initiated.

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Section: Discussionmentioning

confidence: 55%

Section: The Adverse Effects Of Sodium Arsenite On Protein Maturation Can Be Reversed Via Addition Of the Reducing Agent Dttmentioning

confidence: 97%

Examining the function and regulation of hsp 70 in cells subjected to metabolic stress

Beckmann

Lovett

Welch

1992

The Journal of Cell Biology

233

112

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“…Additionally, both As(III) and As(V) have been shown to induce heat-shock response proteins such as dnaJ , dnaK , and grpE in bacteria Leuconostoc esenteroides, Pseudomonas aeruginosa, and Klebsiella pneumoniae. − However, these stress-response genes were not upregulated in Dhc195 under As(III) or As(V) stress in this study (DET1399-1400, 1411). Arsenic is also known to interact with sulfur-containing enzymes directly, which may impact multiple cellular processes. − Iron–sulfur clusters are common in bacterial proteins, and a variety of proteins in Dhc195 contain iron–sulfur units, including reductive dehalogenases and formate dehydrogenase (DET0112), the latter of which was upregulated under As(III)-amended conditions. Because As(III) and As(V) are otherwise known to act via different modes of toxicity, many of these shared gene expression changes may be related to the general stress response in Dhc195.…”

Section: Resultsmentioning

confidence: 99%

“…18,19 Arsenite [As(III)] has been shown to cause toxicity to cells by binding to protein sulfhydryl groups, thereby inhibiting enzymatic catalysis. 20,21 Previous studies also reported that, while As(III) has a higher affinity for sulfhydryl groups, As(V) also interacts with them, but at much higher concentrations. 22 There is a consensus in the literature that the solubilization of arsenic is most common during perturbed redox conditions (i.e., oxidative to reductive) which is typical during in situ reductive dehalogenation when fermentable substrates are amended to generate a reducing environment.…”

Section: ■ Introductionmentioning

confidence: 98%

“…Detoxification of As(V) in bacteria is achieved through reduction of As(V) to As(III) and subsequent export from the cell, and D. mccartyi strains have been reported to contain the arsenic toxicity genes required for this process. , Arsenite [As(III)] has been shown to cause toxicity to cells by binding to protein sulfhydryl groups, thereby inhibiting enzymatic catalysis. , Previous studies also reported that, while As(III) has a higher affinity for sulfhydryl groups, As(V) also interacts with them, but at much higher concentrations …”

Section: Introductionmentioning

confidence: 99%

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Effects of Arsenic on Trichloroethene–Dechlorination Activities of Dehalococcoides mccartyi 195

Gushgari-Doyle

Alvarez‐Cohen

2020

Environ. Sci. Technol.

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Arsenic and trichloroethene (TCE) are among the most prevalent groundwater contaminants in the United States. Cocontamination of these two compounds has been detected at 63% of current TCE-contaminated National Priorities List sites. When in situ TCE reductive dechlorination is stimulated by the addition of fermentable substrates to generate a reducing environment, the presence of arsenic can be problematic because of the potential for increased mobilization and toxicity caused by the reduction of arsenate [As(V)] to arsenite [As(III)]. This study assesses the effects of arsenic exposure on the TCE-dechlorinating activities of Dehalococcoides mccartyi strain 195. Our results indicate that 9.1 μM As(III) caused a 50% decrease in D. mccartyi cell growth. While As(V) concentrations up to 200 μM did not initially impact TCE dechlorination, inhibition was observed in cultures amended with 200 μM As(V) and 100 μM As(V) in 12 and 17 days, respectively, corresponding with the accumulation of As(III). Transcriptomic and metabolomic analyses were performed to evaluate cellular responses to both As(V) and As(III) stress. Amendment of amino acids enhanced arsenic tolerance of D. mccartyi. Results from this study improve our understanding of potential inhibitions of D. mccartyi metabolism caused by arsenic and can inform the design of bioremediation strategies at co-contaminated sites.

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