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Arsenic MOA

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The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Proteomic analysis of arsenite - Mediated multiple antibiotic resistance in Yersinia enterocolitica biovar 1A

Authors: Mallik, S; Virdi, JS; Johri, AK (In Press) Journal of Basic Microbiology. HERO ID: 1003606

[Less] Arsenic is one of the most important global environmental pollutants. In the present study, fifty one . . . [More] Arsenic is one of the most important global environmental pollutants. In the present study, fifty one clinical strains of Yersinia enterocolitica biovar 1A showed high resistance to arsenite and arsenate. The minimum inhibitory concentration (MIC) of arsenite (0.625-20 mM) was lower than arsenate (10-80 mM). Growth of Y. enterocolitica in 2 mM arsenite led to 2-8 fold increase in MICs of the five antibiotics (amikacin, ciprofloxacin, gentamycin, kanamycin and tetracycline), suggesting expression of arsenite-induced multiple antibiotic resistance among the strains. Proteomic analysis of Y. enterocolitica revealed differential expression of certain proteins following arsenite exposure, which included a putative outer membrane porin (OmpA) and a putative amino acid transporter protein. In conclusion, modulation of membrane permeability may be involved in the induction of arsenite-mediated expression of multiple antibiotic resistance in Y. enterocolitica. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

A periplasmic arsenite-binding protein involved in regulating arsenite oxidation

Authors: Liu, G; Liu, M; Kim, E-H; Matty, WS; Bothner, B; Lei, B; Rensing, C; Wang, G; McDermott, TR (In Press) Environmental Microbiology. HERO ID: 1003591

[Less] Arsenic (As) is the most common toxic element in the environment, ranking first on the Superfund List . . . [More] Arsenic (As) is the most common toxic element in the environment, ranking first on the Superfund List of Hazardous Substances. Microbial redox transformations are the principal drivers of As chemical speciation, which in turn dictates As mobility and toxicity. Consequently, in order to manage or remediate environmental As, land managers need to understand how and why microorganisms react to As. Studies have demonstrated a two-component signal transduction system comprised of AioS (sensor kinase) and AioR (response regulator) is involved in regulating microbial AsIII oxidation, with the AsIII oxidase structural genes aioB and aioA being upregulated by AsIII. However, it is not known whether AsIII is first detected directly by AioS or by an intermediate. Herein we demonstrate the essential role of a periplasmic AsIII-binding protein encoded by aioX, which is upregulated by AsIII. An ΔaioX mutant is defective for upregulation of the aioBA genes and consequently AsIII oxidation. Purified AioX expressed without its TAT-type signal peptide behaves as a monomer (MW 32 kDa), and Western blots show AioX to be exclusively associated with the cytoplasmic membrane. AioX binds AsIII with a K(D) of 2.4 µM AsIII; however, mutating a conserved Cys108 to either alanine or serine resulted in lack of AsIII binding, lack of aioBA induction, and correlated with a negative AsIII oxidation phenotype. The discovery and characterization of AioX illustrates a novel AsIII sensing mechanism that appears to be used in a range of bacteria and also provides one of the first examples of a bacterial signal anchor protein.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Arsenite exposure altered the expression of NMDA receptor and postsynaptic signaling proteins in rat hippocampus

Authors: Luo, J-H; Qiu, Z-Q; Zhang, L; Shu, W-Q (In Press) Toxicology Letters. HERO ID: 1015663

[Less] Chronic arsenic exposure has an adverse effect on neurobehavioral function. Our previous study demonstrated . . . [More] Chronic arsenic exposure has an adverse effect on neurobehavioral function. Our previous study demonstrated an elevated arsenic level, ultra-structure changes and reduced NR2A gene expression in hippocampus, and impaired spatial learning in arsenite-exposed rats. The NMDA receptor and the postsynaptic signaling proteins CaMKII, postsynaptic density protein 95 (PSD-95), synaptic Ras GTPase-activating protein (SynGAP) and nuclear activated extracellular-signal regulated kinase (ERK1/2) play important roles in synaptic plasticity, learning and memory. We hypothesized that the above molecular expression changes may contribute to arsenic neurotoxicity. In present study, the expression of NMDA receptor and postsynaptic signaling proteins in hippocampus were evaluated in rats exposed to 0, 2.72, 13.6 and 68mg/L sodium arsenite for 3 months. Decreased protein expression of NR2A, PSD-95 and p-CaMKII α in the hippocampus of arsenite-exposed rats was observed, while the expression of SynGAP, a negative regulator of Ras-MAPK activity, was increased when compared with the controls. Additionally, decreased p-ERK1/2 activity was found in the hippocampus of arsenite-exposed rats. These data suggest that altered expression of NMDA receptor complex and postsynaptic signaling proteins may explain arsenic-induced neurotoxicity.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Photovoltaic device on a single ZnO nanowire p-n homojunction

Authors: Cho, HD; Zakirov, AS; Yuldashev, SU; Ahn, CW; Yeo, YK; Kang, TW (In Press) Nanotechnology. HERO ID: 1015707

[Less] A photovoltaic device was successfully grown solely based on the single ZnO p-n homojunction nanowire. . . . [More] A photovoltaic device was successfully grown solely based on the single ZnO p-n homojunction nanowire. The ZnO nanowire p-n diode consists of an as-grown n-type segment and an in situ arsenic-doped p-type segment. This p-n homojunction acts as a good photovoltaic cell, producing a photocurrent almost 45 times larger than the dark current under reverse-biased conditions. Our results demonstrate that the present ZnO p-n homojunction nanowire can be used as a self-powered ultraviolet photodetector as well as a photovoltaic cell, which can also be used as an ultralow electrical power source for nanoscale electronic, optoelectronic and medical devices.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Arsenate toxicity and stress responses in the freshwater ciliate Tetrahymena pyriformis

Authors: Zhang, Y-Y; Yang, J; Yin, X-X; Yang, S-P; Zhu, Y-G (In Press) European Journal of Protistology. HERO ID: 1015745

[Less] The arsenic metabolism in different biological organisms has been studied extensively. However, little . . . [More] The arsenic metabolism in different biological organisms has been studied extensively. However, little is known about protozoa. Herein, we investigated the cell stress responses of the freshwater ciliate Tetrahymena pyriformis to arsenate toxicity. An acute toxicity assay revealed an 18-h EC(50) arsenate concentration of ca. 40μM, which caused significant changes in the cell shape, growth and organism mobility. Whereas, under exposure to 30μM arsenate, T. pyriformis could grow reasonably well, indicating a certain resistance of this organism. Arsenic speciation analysis revealed that 94-98% of the total arsenate in cells of T. pyriformis could be transformed to monomethylarsonic acid, dimethylarsinic acid and a small proportion of arsenite after 18h of arsenate exposure, thus indicating the major detoxification pathway by arsenic oxidation/reduction and biomethylation. Finally, comparative proteomic analysis unveiled significant changes in the expression of multiple proteins involved in anti-oxidation, sugar and energy metabolism, proteolysis, and signal transduction. Our results revealed multiple pathways of arsenate detoxification in T. pyriformis, and indicated that protozoa may play important roles in the biogeochemical cycles of arsenic.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Field Testing of Arsenic in Groundwater Samples of Bangladesh Using a Test Kit Based on Lyophilized Bioreporter Bacteria

Authors: Siegfried, K; Endes, C; Bhuiyan, AF; Kuppardt, A; Mattusch, J; van der Meer, JR; Chatzinotas, A; Harms, H (In Press) Environmental Science and Technology. HERO ID: 1015751

[Less] A test kit based on living, lyophilized bacterial bioreporters emitting bioluminescence as a response . . . [More] A test kit based on living, lyophilized bacterial bioreporters emitting bioluminescence as a response to arsenite and arsenate was applied during a field campaign in six villages across Bangladesh. Bioreporter field measurements of arsenic in groundwater from tube wells were in satisfying agreement with the results of spectroscopic analyses of the same samples conducted in the lab. The practicability of the bioreporter test in terms of logistics and material requirements, suitability for high sample throughput, and waste disposal was much better than that of two commercial chemical test kits that were included as references. The campaigns furthermore demonstrated large local heterogeneity of arsenic in groundwater, underscoring the use of well switching as an effective remedy to avoid high arsenic exposure.

Journal Article
Journal Article

Silibinin potentially protects arsenic-induced oxidative hepatic dysfunction in rats

Authors: Muthumani, M; Prabu, SM (In Press) Toxicology Mechanisms and Methods. HERO ID: 1015878

[Less] Arsenic (As) compounds are reported as environmental toxicants and human carcinogens. Exposure to arsenic . . . [More] Arsenic (As) compounds are reported as environmental toxicants and human carcinogens. Exposure to arsenic imposes a big health issue worldwide. Silibinin (SB) is a major flavonolignan compound of silimarin and is found in milk thistle of Silybum marianum. It has been reported that silibinin has antioxidant efficacy as metal chelators due to the orientation of its functional groups. However, it has not yet been explored in experimental animals. In view of this fact, the purpose of this study was to delineate the ameliorative role of silibinin against arsenic-induced hepatotoxicity in rats. Rats were orally treated with arsenic alone (5 mg/kg body weight (bw)/day) plus silibinin (75 mg/kg bw/day) for 4weeks. Hepatotoxicity was evaluated by the increased activities of serum hepatospecific enzymes namely aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma glutamyl transferase, lactate dehydrogenase and total bilirubin along with increased elevation of lipid peroxidative markers, thiobarbituric acid reactive substances, lipid hydroperoxides, protein carbonyl content and conjugated dienes. The toxic effect of arsenic was also indicated by significantly decreased activities of membrane bound ATPases, enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase along with nonenzymatic antioxidants like reduced glutathione, total sulfhydryl groups, vitamins C and E. Administration of silibinin exhibited a significant reversal of arsenic-induced toxicity in hepatic tissue. All these changes were supported by reduction of DNA damage in hepatocytes and histopathological observations of the liver. These results suggest that silibinin has a potential protective effect over arsenic-induced hepatotoxicity in rat.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Antiapoptotic efficacy of folic acid and vitamin B(12) against arsenic-induced toxicity

Authors: Majumdar, S; Maiti, A; Karmakar, S; Sekhar Das, A; Mukherjee, S; Das, D; Mitra, C (In Press) Environmental Toxicology. HERO ID: 1017429

[Less] Earlier, we proposed that the ability of folic acid and vitamin B(12) to preserve systemic and mitochondrial . . . [More] Earlier, we proposed that the ability of folic acid and vitamin B(12) to preserve systemic and mitochondrial function after short-term exposure to arsenic may prevent further progression to more permanent injury and pathological changes leading to cell death. To elucidate its mechanism, the present study examined the antiapoptotic efficacy of folic acid and vitamin B(12) against short-term arsenic exposure-induced hepatic mitochondria oxidative stress and dysfunction. Sixteen to eighteen weeks old male albino rats weighing 140-150 × g were divided into five groups: Control (A), Arsenic-treated (B), Arsenic + folic acid (C), Arsenic +vitamin B(12) (D), and Arsenic + folic acid + vitamin B(12) (E). Data generated indicated that folic acid and vitamin B(12) separately or in combination can give significant protection against alterations in oxidative stress and apoptotic marker parameters and downstream changes in mitochondria, namely pro-oxidative (NO, TBARS, OH(-)) and antioxidative defense (SOD, CAT, GSH) markers, iNOS protein expression, mitochondrial swelling, cytochrome c oxidase and Ca(2+)-ATPase activity, Ca(2+) content, caspase-3 activity. Additionally, results of hepatic cell DNA fragmentation, arsenic load of blood, hepatic tissue and urine, and histological observations, all strongly support that both these supplements have efficacy in preventing apoptotic changes and cellular damage. As the mechanisms of actions of both of these supplements are methylation related, a combined application was more effective. Results further reveal new molecular targets through which folic acid and vitamin B(12) separately or in combination work to alleviate one critical component of arsenic-induced liver injury: mitochondria dysfunction. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Genotoxic potential of arsenic at its reference dose

Authors: Kesari, VP; Kumar, A; Khan, PK (In Press) Ecotoxicology and Environmental Safety. HERO ID: 1015662

[Less] Arsenic, a highly hazardous contaminant in our drinking water, accounts for various toxic effects (including . . . [More] Arsenic, a highly hazardous contaminant in our drinking water, accounts for various toxic effects (including cancer) in human. However, intake of arsenic @0.3μgkg(-1)day(-1) through drinking water, containing arsenic at its guideline value or maximum contaminant limit (10μgL(-1)), has been estimated to pose very little or no measurable risk to cancer in humans. The value also appears to be equal to the human reference dose (or index dose) of arsenic based on human skin toxicity data. The present work was a quantitative assessment of the genotoxic potential of arsenic in mice at doses equivalent to its human reference dose as well as its multiples. Significant increases in the frequencies of chromosome abnormalities in the bone marrow cells were registered over the control level upon exposure to all the doses of arsenic including its reference dose (or index dose). The assessment of arsenic genotoxicity in humans at low doses will therefore be highly instrumental in establishing a permissible limit of arsenic in drinking water.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Solution structure of Mycobacterium tuberculosis NmtR in the Apo state: Insights into Ni(II)-mediated allostery

Authors: Lee, CW; Chakravorty, DK; Chang, F-MJ; Reyes-Caballero, H; Ye, Y; Merz, KM, Jr; Giedroc, DP (In Press) Biochemistry. HERO ID: 1015682

[Less] Mycobacterium tuberculosis is an obligate human respiratory pathogen that encodes approximately 10 arsenic . . . [More] Mycobacterium tuberculosis is an obligate human respiratory pathogen that encodes approximately 10 arsenic repressor (ArsR) family regulatory proteins that allow the organism to respond to a wide range of changes in its immediate microenvironment. How individual ArsR repressors have evolved to respond to selective stimuli is of intrinsic interest. The Ni(II)/Co(II)-specific repressor NmtR and related actinomycete nickel sensors harbor a conserved N-terminal α-NH(2)-Gly2-His3-Gly4 sequence. Here, we present the solution structure of homodimeric apo-NmtR and show that the core of the molecule adopts a typical winged-helix ArsR repressor (α1-α2-α3-αR-β1-β2-α5) "open conformation" that is similar to that of the related zinc sensor Staphylococcus aureus CzrA, but harboring long, flexible N-terminal (residues 2-16) and C-terminal (residues 109-120) extensions. Binding of Ni(II) to the regulatory sites induces strong paramagnetic broadening of the α5 helical region and the extreme N-terminal tail to residue 10. Ratiometric pulse chase amidination mass spectrometry reveals that the rate of amidination of the α-amino group of Gly2 is strongly attenuated in the Ni(II) complex relative to the apo state and noncognate Zn(II) complex. Ni(II) binding also induces dynamic disorder on the microsecond to millisecond time scale of key DNA interacting regions that likely contributes to the negative regulation of DNA binding by Ni(II). Molecular dynamics simulations and quantum chemical calculations reveal that NmtR readily accommodates a distal Ni(II) hexacoordination model involving the α-amine and His3 of the N-terminal region and α5 residues Asp91', His93', His104, and His107, which collectively define a new metal sensing site configuration in ArsR family regulators.