Arsenic impairs the lineage commitment of hematopoietic progenitor cells through the attenuation of GATA-2 DNA binding activity.

Arsenic exposure produces significant hematotoxicity in vitro and in vivo. Our previous work shows that arsenic (in the form of arsenite, AsIII) interacts with the zinc finger domains of GATA-1, inhibiting the function of this critical transcription factor, and resulting in the suppression of erythropoiesis. In addition to GATA-1, GATA-2 also plays a key role in the regulation of hematopoiesis. GATA-1 and GATA-2 have similar zinc finger domains (C4-type) that are structurally favorable for AsIII interactions. Taking this into consideration, we hypothesized that early stages of hematopoietic differentiation that are dependent on the function of GATA-2 may also be disrupted by AsIII exposure. We found that in vitro AsIII exposures disrupt the erythromegakaryocytic lineage commitment and differentiation of erythropoietin-stimulated primary mouse bone marrow hematopoietic progenitor cells (HPCs), producing an aberrant accumulation of cells in early stages of hematopoiesis and subsequent reduction of committed erythro-megakaryocyte progenitor cells. Arsenic significantly accumulated in the GATA-2 protein, causing the loss of zinc, and disruption of GATA-2 function, as measured by chromatin immunoprecipitation and the expression of GATA-2 responsive genes. Our results show that the attenuation of GATA-2 function is an important mechanism contributing to the aberrant lineage commitment and differentiation of early HPCs. Collectively, findings from the present study suggest that the AsIII-induced disruption of erythro-megakaryopoiesis may contribute to the onset and/or exacerbation of hematological disorders, such as anemia.

Combined toxicity of arsenite and dimethylarsenic acid on the freshwater diatom Nitzschia palea.

The toxicity and bioavailability of single arsenic species have been widely investigated, however, the biological effects of mixed arsenic species co-existing in natural waters still remain unknown. The objective of this work was to discern the adverse effects of combined arsenite (As(III)) and dimethylarsenic acid (DMA) on diatom Nitzschia palea. The combined ecotoxicity of As(III) and DMA on N. palea was observed to be time-dependent and showed dose-effect relation. The toxicity of DMA and As(III) mixture was higher than individual DMA or As(III) when the As(III) concentration was in the range of 0.085-0.316 mg L-1. As the As(III) concentration increased from 0.487 to 0.858 mg L-1, the antagonistic effect was found, which could be due to the higher thiols contents in the thiol-containing proteins (e.g., frustulins, silaffins and other glycoproteins). The content of malondialdehyde (MDA) in the treatment of mixed arsenic species was found to be at the same level compared to the As-free control after 72 h of exposure, indicating that the co-toxicity of As(III) and DMA on diatom frustules was not significant. Furthermore, the increase of frustule formation rate in the mixture of EC50 As(III)-EC10 DMA at 72 h exposure time indicated that the damaged diatom cell walls was likely repaired gradually. The results from this study suggested that the effects of co-existed arsenic species were concentration-specific and should be considered in the risk assessment of arsenic and development of water quality criteria for the protection of aquatic ecosystems.

An aquaporin PvTIP4;1 from Pteris vittata may mediate arsenite uptake.

The fern Pteris vittata is an arsenic hyperaccumulator. The genes involved in arsenite (As(III)) transport are not yet clear. Here, we describe the isolation and characterization of a new P. vittata aquaporin gene, PvTIP4;1, which may mediate As(III) uptake. PvTIP4;1 was identified from yeast functional complement cDNA library of P. vittata. Arsenic toxicity and accumulating activities of PvTIP4;1 were analyzed in Saccharomyces cerevisiae and Arabidopsis. Subcellular localization of PvTIP4;1-GFP fusion protein in P. vittata protoplast and callus was conducted. The tissue expression of PvTIP4;1 was investigated by quantitative real-time PCR. Site-directed mutagenesis of the PvTIP4;1 aromatic/arginine (Ar/R) domain was studied. Heterologous expression in yeast demonstrates that PvTIP4;1 was able to facilitate As(III) diffusion. Transgenic Arabidopsis showed that PvTIP4;1 increases arsenic accumulation and induces arsenic sensitivity. Images and FM4-64 staining suggest that PvTIP4;1 localizes to the plasma membrane in P. vittata cells. A tissue location study shows that PvTIP4;1 transcripts are mainly expressed in roots. Site-directed mutation in yeast further proved that the cysteine at the LE1 position of PvTIP4;1 Ar/R domain is a functional site. PvTIP4;1 is a new represented tonoplast intrinsic protein (TIP) aquaporin from P. vittata and the function and location results imply that PvTIP4;1 may be involved in As(III) uptake.

pH modulates arsenic toxicity in Bacillus licheniformis DAS-2.

The toxic characteristics of arsenic species, As(V) and As(III) result in ecological risks. Arsenic tolerant bacterium was isolated and identified as the Bacillus licheniformis DAS-2 through 16SrDNA sequencing. B. licheniformis DAS-2 was efficient to tolerate and remove both the As(V)[MIC 8mM] and As(III)[MIC 6mM] from the growth medium. The potential for the removal/uptake of arsenic from the 3, 5 and 7mM As(V) enriched growth media was 100%, 60% and 35% respectively and from the 1, 3 and 5mM As(III) enrichment it was 100%, 99% and 58% respectively at neutral pH. 80% of uptake As(V) was reduced to As(III) in 3mM As(V) enrichment which was gradually decreased to only 17% at 7mM As(V) enrichment at neutral pH. The arsenic toxicity in B. licheniformis DAS-2 was found modulated by pH and was examined through alteration in growth, uptake/removal, reduction and measurement of chemical toxicity.

Adsorptive removal of As(III) ions from water using spent grain modified by polyacrylamide.

In order to enhance the removal efficiency of As(III), a pre-oxidation process is generally applied first to convert As(III) to As(V), which may cause unwanted new contaminants. To overcome this problem, efforts were made to develop an effective way to remove As(III) directly without an oxidation step. The effect of polyacrylamide polymers (PAMs) such as anionic PAM, cationic PAM and nonionic PAM, on As(III) ion adsorption by spent grain (SG) was investigated. The physico-chemical properties of the three PAM-polymerized SGs (APSG (anionic PAM-polymerized modified spent grain), CPSG (cationic PAM-polymerized spent grain) and NPSG (nonionic PAM-polymerized spent grain)) were analyzed using Fourier transform infrared (FT-IR), scanning electron microscope (SEM) and zeta potential. Batch experimental data showed that the sequence of preferential adsorption for As(III) was APSG>CPSG>NPSG. Active functional groups such as amino group (NH2), carbonyl group (CO), C-N bond of the amide group (CONH2), and hydroxyl group (O-H) were responsible for As(III) adsorption. Many tubular structures occurring on the surface of APSG possibly increase the specific surface areas and favor the adsorption of As(III) ions. A fixed-bed study was carried out by using APSG as an adsorbent for As(III) from water. Three factors such as bed height, initial concentration and flow rate were studied, and breakthrough curves of As(III) were obtained. The Adams-Bohart model was used to analyze the experimental data and the model parameters were evaluated.

Arsenite Methyltransferase Is an Important Mediator of Hematotoxicity Induced by Arsenic in Drinking Water.

Chronic arsenic exposures via the consumption of contaminated drinking water are clearly associated with many deleterious health outcomes, including anemia. Following exposure, trivalent inorganic arsenic (AsIII) is methylated through a series of arsenic (+III oxidation state) methyltransferase (As3MT)-dependent reactions, resulting in the production of several intermediates with greater toxicity than the parent inorganic arsenicals. The extent to which inorganic vs. methylated arsenicals contribute to AsIII-induced hematotoxicity remains unknown. In this study, the contribution of As3MT-dependent biotransformation to the development of anemia was evaluated in male As3mt-knockout (KO) and wild-type, C57BL/6J, mice following 60-day drinking water exposures to 1 mg/L (ppm) AsIII. The evaluation of hematological indicators of anemia revealed significant reductions in red blood cell counts, hemoglobin levels, and hematocrit in AsIII-exposed wild-type mice as compared to unexposed controls. No such changes in the blood of As3mt-KO mice were detected. Compared with unexposed controls, the percentages of mature RBCs in the bone marrow and spleen (measured by flow cytometry) were significantly reduced in the bone marrow of AsIII-exposed wild-type, but not As3mt-KO mice. This was accompanied by increased levels of mature RBCS in the spleen and elevated levels of circulating erythropoietin in the serum of AsIII-exposed wild-type, but not As3mt-KO mice. Taken together, the findings from the present study suggest that As3MT-dependent biotransformation has an essential role in mediating the hematotoxicity of AsIII following drinking water exposures.

OFF-switching property of quorum sensor LuxR via As(III)-induced insoluble form.

Whole-cell sensors for arsenite detection have been developed exclusively based on the natural arsenite (As(III)) sensory protein ArsR for arsenic metabolism. This study reports that the quorum-sensing LuxR/Plux system from Vibrio fischeri, which is completely unrelated to arsenic metabolism, responds to As(III) in a dose-dependent manner. Due to as many as 9 cysteine residues, which has a high binding affinity with As(III), LuxR underwent As(III)-induced insoluble form, thereby reducing its effective cellular concentration. Accordingly, the expression level of green fluorescent protein under the control of Plux gradually decreased with increasing As(III) concentration in the medium. This is a novel As(III)-detection system that has never been proposed before, with a unique ON-to-OFF transfer function.

Phosphorus-arsenic interaction in the 'soil-plant-microbe' system and its influence on arsenic pollution.

Elevated arsenic (As) in soil is of public concern due to the carcinogenicity. Phosphorus (P) strongly influences the adsorption, absorption, transport, and transformation of As in the soil and in organisms due to the similarity of the chemical properties of P and As. In soil, P, particularly inorganic P, can release soil-retained As (mostly arsenate) by competing for adsorption sites. In plant and microbial systems, P usually reduces As (mainly arsenate) uptake and affects As biotransformation by competing for As transporters. The intensity and pattern of PAs interaction are highly dependent on the forms of As and P, and strongly influenced by various biotic and abiotic factors. An understanding of the PAs interaction in 'soil-plant-microbe' systems is of great value to prevent soil As from entering the human food chain. Here, we review PAs interactions and the main influential factors in soil, plant, and microbial subsystems and their effects on the As release, absorption, transformation, and transport in the 'soil-plant-microbe' system. We also analyze the application potential of P fertilization as a control for As pollution and suggest the research directions that need to be followed in the future.

Biohybrid Hydrogel and Aerogel from Self-Assembled Nanocellulose and Nanochitin as a High-Efficiency Adsorbent for Water Purification.

A simple and novel method, self-assembly of nanocellulose and nanochitin, was developed to produce high-efficiency and versatile biohybrid hydrogel (BHH) and aerogel (BHA) for water purification. The self-assembly process was driven by the electrostatic force between one-dimensional (1D) negatively charged TEMPO-oxidized cellulose nanofiber (TOCNF) and positively charged partly deacetylated chitin nanofiber (PDChNF). The self-assembly process was performed at room temperature and without adding any cross-linking agents throughout the process. This results in the three-dimensional (3D) BHH that physically cross-linked via both electrostatic interactions and hydrogen bonding between TOCNF and PDChNF. The obtained BHA from lyophilized BHH exhibited a highly porous interconnected structure with a specific surface area of 54 m2·g-1, which assures the availability of its internal active site for the adsorption of toxic metalloid ions and organic pollutants. Consequently, the BHA displayed super-high adsorption capacities of 217 mg·g-1 for As(III) under the neutral pH conditions and 531 mg·g-1 for methylene blue (MB) under an alkaline aqueous condition with rapid adsorption kinetics, in sharp contrast to conventional biobased adsorbents. Moreover, the BHA is reusable, which still exhibited a high MB adsorption capacity of 505 mg·g-1 even after five successive adsorption-desorption cycles. This versatile BHA produced via a facile preparation strategy is proven to be a promising renewable adsorbent for water purification, offering simple and green alternatives to the conventional adsorbent from synthetic polymers.

Differential transcriptional regulation of hypoxia-inducible factor-1α by arsenite under normoxia and hypoxia: involvement of Nrf2.

Arsenite (As(III)) is widely distributed in nature and can be found in water, food, and air. There is significant evidence that exposure to As(III) is associated with human cancers originated from liver, lung, skin, bladder, kidney, and prostate. Hypoxia plays a role in tumor growth and aggressiveness; adaptation to it is, at least to a large extent, mediated by hypoxia-inducible factor-1α (HIF-1α). In the current study, we investigated As(III) effects on HIF-1α under normoxia and hypoxia in the hepatoma cell line HepG2. We found that As(III) increased HIF-1α protein levels under normoxia while the hypoxia-mediated induction of HIF1α was reduced. Thereby, the As(III) effects on HIF-1α were dependent on both, transcriptional regulation via the transcription factor Nrf2 mediated by NOX4, PI3K/Akt, and ERK1/2 as well as by modulation of HIF-1α protein stability. In line, the different effects of As(III) via participation of HIF-1α and Nrf2 were also seen in tube formation assays with endothelial cells where knockdown of Nrf2 and HIF-1α abolished As(III) effects. Overall, the present study shows that As(III) is a potent inducer of HIF-1α under normoxia but not under hypoxia which may explain, in part, its carcinogenic as well as anti-carcinogenic actions. KEY MESSAGE: As(III) increased HIF-1α under normoxia but reduced its hypoxia-dependent induction. The As(III) effects on HIF-1α were dependent on ROS, NOX4, PI3K/Akt, and ERK1/2. The As(III) effects under normoxia involved transcriptional regulation via Nrf2. Knockdown of Nrf2 and HIF-1α abolished As(III) effects in tube formation assays. The data may partially explain As(III)'s carcinogenic and anti-carcinogenic actions.