Effect of sodium arsentie on the induction and turnover of ornithine decarboxylase activity in erythroleukemia cells

Flamigni, Flavio; Marmiroli, Sandra; Caldarera, Claudio Marcello; Guarnieri, Carlo

doi:10.1002/cbf.290070310

Cited by 10 publications

(3 citation statements)

References 23 publications

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“…To our knowledge, the only route of D‐5‐oxoproline synthesis (increased abundance in As(III)) involves glutamate in an ATP‐depleting futile cycle that includes γ‐glutamyl phosphate (Emmett, ). We also note that ornithine decarboxylase activity is enhanced/stabilized by As(III) in erythroleukemia cells (Flamigni et al ., ), rat hepatic cells (Brown et al ., ) and in Leishmania (Haimeur et al ., ). To the extent that this also occurs in bacteria such as A. tumefaciens 5A, this would promote putrescine synthesis, as observed here (Fig.…”

Section: Discussionmentioning

confidence: 99%

Metabolic response of Agrobacterium tumefaciens 5A to arsenite

Tokmina‐Lukaszewska

Shi

Tripet

et al. 2017

Environmental Microbiology

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Wide-spread abundance in soil and water, coupled with high toxicity have put arsenic at the top of the list of environmental contaminants. Early studies demonstrated that both concentration and the valence state of inorganic arsenic (arsenite, As(III) vs. arsenate As(V)) can be modulated by microbes. Using genetics, transcriptomic and proteomic techniques, microbe-arsenic detoxification, respiratory As(V) reduction and As(III) oxidation have since been examined. The effect of arsenic exposure on whole-cell intracellular microbial metabolism, however, has not been extensively studied. We combined LC-MS and H NMR to quantify metabolic changes in Agrobacterium tumefaciens (strain 5A) upon exposure to sub-lethal concentrations of As(III). Metabolomics analysis reveals global differences in metabolite concentrations between control and As(III) exposure groups, with significant perturbations to intermediates shuttling into and cycling within the TCA cycle. These data are most consistent with the disruption of two key TCA cycle enzymes, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. Glycolysis also appeared altered following As(III) stress, with carbon accumulating as complex saccharides. These observations suggest that an important consequence of As(III) contamination in nature will be to alter microbial carbon metabolism at the microbial community level and thus has the potential to foundationally impact all biogeochemical cycles in the environment.

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Section: Discussionmentioning

confidence: 99%

Metabolic response of Agrobacterium tumefaciens 5A to arsenite

Tokmina‐Lukaszewska

Shi

Tripet

et al. 2017

Environmental Microbiology

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“…Similarly, the ODC gene is amplified or overexpressed in a number of mammalian cells selected for growth resistance to DFMO (McConlogue et al ., 1986; McCann and Pegg, 1992). Arsenite can apparently increase the half‐life of the mammalian ODC (Flamigni et al ., 1989), and ODC activity was also recently found to be increased in rats in which arsenite was administered orally (Brown and Kitchin, 1996). Arsenite selection increases GSH levels in mammalian cells (Chen et al ., 1997; Lee et al ., 1989) and, as TSH is the major reduced thiol in Leishmania , the increased levels of GSH and spermidine in arsenite‐resistant Leishmania are not unexpected.…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of polyamines and trypanothione resulting from overexpression of the ornithine decarboxylase gene in arsenite‐resistant Leishmania

Haimeur

Guimond

Pilote

et al. 1999

Molecular Microbiology

126

106

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SummaryThe levels of trypanothione, a glutathione±spermidine conjugate, are increased in the protozoan parasite Leishmania selected for resistance to the heavy metal arsenite. The levels of putrescine and spermidine were increased in resistant mutants. This increase is mediated by overexpression of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Gene overexpression is generally mediated by gene ampli®cation in Leishmania but, here, the mRNA and the enzymatic activity of ODC are increased without gene ampli®cation. This RNA overexpression is stable when cells are grown in the absence of the drug and does not result from gene rearrangements or from an increased rate of RNA synthesis. Transient transfections suggest that mutations in the revertant cells contribute to these elevated levels of RNA. Stable transfection of the ODC gene increases the level of trypanothione, which can contribute to arsenite resistance. In addition to ODC overexpression, the gene for the ABC transporter PGPA is ampli®ed in the mutants. The co-transfection of the ODC and PGPA genes confers resistance in a synergistic fashion in partial revertants, also suggesting that PGPA recognizes metals conjugated to trypanothione.

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“…MEL cells containing cassette 234 at RL1 (1) were incubated with either cycloheximide (20 or 60 g/ml) or actinomycin D (5 or 30 g/ml) (11,12,27,30,42), aliquots were taken every 2 h, and LacZ expression was evaluated by chemiluminescence on protein extract as described elsewhere (1). For both drugs, similar kinetics of ␤-Gal decay were obtained with both concentrations tested.…”

Section: Methodsmentioning

confidence: 99%

Enhancer-Dependent Transcriptional Oscillations in Mouse Erythroleukemia Cells

Alami

Bouhassira

1999

Molecular and Cellular Biology

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By using recombinase-mediated cassette exchange, a method that allows integration of single copies of different constructs at the same predetermined chromosomal location, several expression cassettes have been integrated at a randomly chosen locus in the genome of mouse erythroleukemia cells. The cassettes studied contain the human ␤-globin promoter fused to lacZ coding sequences either alone or linked to DNase I-hypersensitive site HS2, HS3, or HS234 (a large locus control region fragment containing HS2, HS3, and HS4) of the human ␤-globin locus control region. Analysis of expression of these cassettes revealed mosaic expression patterns reminiscent of, but clearly different from, position effect variegation. Further investigations demonstrated that these mosaic expression patterns are caused by dynamic activation and inactivation of the transcription unit, resulting in oscillations of expression. These oscillations occur once in every few cell cycles at a rate specific for the enhancer present at the locus. DNase I sensitivity studies revealed that the chromatin is accessible and that DNase-hypersensitive sites were present whether or not the transcription unit is active, suggesting that the oscillations occur between transcriptionally competent and transcriptionally active chromatin conformations, rather than between open and closed chromatin conformations. Treatment of oscillating cells with trichostatin A eliminates the oscillations only after the cells have passed through late G 1 or early S, suggesting that these oscillations might be caused by changes in histone acetylation patterns.It has long been known that expression of transfected or translocated genes is not always stable and is subject to position effects. In metazoans, the two best-studied such phenomena are heterochromatin-induced position effect variegation (PEV) (24), in which transgenes are clonally inactivated in a fraction of a cell population, and extinction of transgenes in cell culture (50) and transgenic animals (15,35,41,47). We have recently developed a novel method called recombinasemediated cassette exchange (RMCE) that allows integration of single copies of different expression cassettes at the same predetermined chromosomal locations (1). This method is ideally suited to study position effects and gene regulation because interesting chromosomal locations can be identified and then revisited by insertion of different expression cassettes.To study position effects and means to prevent them, we have used as a model components of the human ␤-globin gene cluster. This cluster is located on chromosome 11 and contains five genes that are sequentially expressed during development and are regulated by the locus control region (LCR) (14,34,44). The LCR is located 6 to 20 kb upstream of the ε-globin gene and consists of five DNase I-hypersensitive sites (HSs) first reported by Tuan et al. (48). The importance of the LCR for regulation of the globin genes was inferred from studies of naturally occurring deletions of the LCR that are associate...

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Effect of sodium arsentie on the induction and turnover of ornithine decarboxylase activity in erythroleukemia cells

Cited by 10 publications

References 23 publications

Metabolic response of Agrobacterium tumefaciens 5A to arsenite

Metabolic response of Agrobacterium tumefaciens 5A to arsenite

Elevated levels of polyamines and trypanothione resulting from overexpression of the ornithine decarboxylase gene in arsenite‐resistant Leishmania

Enhancer-Dependent Transcriptional Oscillations in Mouse Erythroleukemia Cells

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