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At least 19 recordsLinked to original sources
PubMed2002

Transport and detoxification systems for transition metals, heavy metals and metalloids in eukaryotic and prokaryotic microbes.

Transition metals, heavy metals and metalloids are usually toxic in excess, but a number of transition metals are essential trace elements. In all cells there are mechanisms for metal ion homeostasis that frequently involve a balance between uptake and efflux systems. This review will briefly describe ATP-coupled resistance pumps. ZntA and CadA are bacterial P-type ATPases that confers resistance to Zn(II), Cd(II) and Pb(II). Homologous copper pumps include the Menkes and Wilson disease proteins and CopA, an Escherichia coli pump that confers resistance to Cu(I). For resistance to arsenicals and antimonials there are several different families of transporters. In E. coli the ArsAB ATPase is a novel system that confers resistance to As(III) and Sb(III). Eukaryotic arsenic resistance transporters include Acr3p and Ycf1p of Saccharomyces cerevisiae. These systems provide resistance to arsenite [As(III)]. Arsenate [As(V)] detoxification involves reduction of As(V) to As(III), a process catalyzed by arsenate reductase enzymes. There are three families of arsenate reductases, two found in bacterial systems and a third identified in S. cerevisiae.

Biological Transport↗
PubMed1998

Renal Na-Si cotransporter NaSi-1 is inhibited by heavy metals.

Heavy metal intoxication leads to a number of reabsorptive and secretory defects in renal transport systems. We have studied the effects of several heavy metals on the expression of the renal Na-Si cotransporter NaSi-1. NaSi-1 cRNA was injected into Xenopus oocytes, and Na-Si cotransport activity was measured in the presence of mercury, lead, cadmium, or chromium. Mercury strongly inhibited NaSi-1 transport irreversibly by reducing both maximal velocity (Vmax) and Michaelis constant (Km) for inorganic sulfate (Si). Lead inhibited NaSi-1 transport reversibly by decreasing Vmax but not Km for Si. Cadmium showed weak reversible inhibition of NaSi-1 transport by decreasing only NaSi-1 Vmax. Chromium strongly inhibited NaSi-1 cotransport reversibly by reducing Km for Si by sevenfold, most probably by binding to the Si site, due to the strong structural similarity between the CrO4(2-) and SO4(2-) substrates. In conclusion, this study presents an initial report demonstrating heavy metals inhibit renal brush border Na-Si cotransport via the NaSi-1 protein through various mechanisms and that this blockade may be responsible for sulfaturia following heavy metal intoxication.

Animals↗
PubMed1992

Evaluation of Drosophila melanogaster as an alternative animal for studying the neurotoxicity of heavy metals.

Heavy metals cause irreversible neurobehavioral damage in many developing mammals, but the mechanisms of this damage are unknown. The influence of three heavy metal compounds, triethyllead chloride, lead acetate and cadmium chloride, on lethality, development, behavior and learning was studied using the fruit fly, Drosophila melanogaster. This animal was used because it allows hundreds of subjects to be assayed very easily in individual experiments and because it is a system in which toxicological questions might be answered by using the techniques of modern molecular genetics. When triethyllead chloride, lead acetate or cadmium chloride was placed in the medium, the larval LC50 (+/- standard error) was found to be 0.090 +/- 0.004, 6.60 +/- 0.64 and 0.42 +/- 0.04 mM, respectively. Each of the tested compounds produced a dose-related delay in development. In particular, they caused a delay in the development of larvae to pupae. When larvae were reared on medium containing triethyllead chloride (0.06 mM), lead acetate (3.07 mM) or cadmium chloride (0.11 mM), phototaxis, locomotion and learning were not inhibited. Since significant neurobehavioral effects were not observed under the experimental conditions used, Drosophila does not appear to be an appropriate animal for the genetic dissection of such effects of heavy metals during development.

Animals↗
PubMed1958

Staining of tissue sections for electron microscopy with heavy metals.

Heavy metals may be incorporated from solution into tissue sections for electron microscopy. The resulting increase in density of the tissue provides greatly enhanced contrast with minimal distortion. Relative densities of various structures are found to depend on the heavy metal ions present and on the conditions of staining. Certain hitherto unobserved details are revealed and some sort of specificity exists, although the factors involved are not yet understood.

Electrons↗
PubMed2000

Novel responses of ZRF, a variant of human MTF-1, to in vivo treatment with heavy metals.

Heavy metal-dependent transcriptional activation of metallothionein (MT) genes is mediated by multiple enhancer sequences, metal responsive element (MRE), located in the upstream region of the genes. Previously, we have reported purification of a zinc-dependent MRE-binding protein, zinc regulatory factor (ZRF), from HeLa cells, and have pointed to the close relationship between ZRF and mouse MRE-binding transcription factor-1 (MTF-1) according to the analysis of partial amino acid sequences. By means of cDNA cloning and the product analyses, we show that ZRF is a variant of human MTF-1 (hMTF-1), which carries a single amino acid exchange in the zinc finger domain. Accordingly, ZRF is renamed hMTF-1b. Expression of hMTF-1b in HeLa cells is constitutive at both mRNA and protein levels, and is unaffected by treatment with cadmium (Cd). On the other hand, when cells were fractionated into nuclear extract and cytosol, a large part of the hMTF-1b was recovered in the cytosol fraction. A significant increase in the amount of nuclear hMTF-1b occurs when cells are treated with various heavy metals, including Cd, Zn, Cu and Ag, which is associated with concomitant decrease in the amount recovered in the cytosol fraction. Since immunocytochemical analysis revealed that intracellular distribution of hMTF-1b is restricted to the nucleus irrespective of the heavy metal treatment, such an increment in the nuclear extracts apparently results from promotion of nuclear retention of hMTF-1b by the heavy metal treatment. Analysis by native gel electrophoresis shows that the mobility of hMTF-1b significantly changes in association with Cd treatment, raising the possibility that a conformational change of hMTF-1b occurs in response to treatment with heavy metals in vivo.

Amino Acid Sequence↗
PubMed2002

Relationship between partition of heavy metals in sewage sludge and elution of heavy metals.

Heavy metals in sewage sludge were classified into three partitions associated with extracellular and intracellular organic matters and the residue before and after different elution processes of heavy metals from the sludge. Alkalization of the sludge to pH 11 decreased the content of Cu in the three partitions and that of Ni in extracellular organic and residual ones. Acidification of the sludge to pH 3 decreased the content of Cd, Mn, Ni and Zn in all of the partitions and that of Cu in the intracellular organic one. A further decrease in the pH to 2 caused a decrease in the content of Cu in extracellular organic and residual partitions and that of Ni in the inorganic one. The addition of ferric sulfate to the sludge effectively lowered the content of Cd and Cu in extracellular organic and inorganic partitions under acidic conditions. These results would give information on a selection of the method for removing heavy metals from the sludge.

Biological Availability↗
PubMedDate not supplied

Increased expression of keratinocyte interleukin-8 in human contact eczematous reactions to heavy metals.

Heavy metal-induced contact eczematous human skin reactions to cobalt chloride and mercuric chloride were investigated for immunoreactivity to interleukin-8 (IL-8), by using an indirect immunoperoxidase staining technique. There was suprabasal epidermal staining for IL-8, with a decrease in the vicinity of areas with parakeratotic epithelium. However, in the immediate vicinity of a vesicular formation, intense staining of some apically situated keratinocytes was found. In addition, increased immunoreactivity over the acrosyringial area compared with the surrounding epidermis was obtained. These findings indicate an increased synthesis of keratinocyte IL-8 in contact eczematous skin.

Cobalt↗
PubMed2004

Effect of the militarily-relevant heavy metals, depleted uranium and heavy metal tungsten-alloy on gene expression in human liver carcinoma cells (HepG2).

Depleted uranium (DU) and heavy-metal tungsten alloys (HMTAs) are dense heavy-metals used primarily in military applications. Chemically similar to natural uranium, but depleted of the higher activity 235U and 234U isotopes, DU is a low specific activity, high-density heavy metal. In contrast, the non-radioactive HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%), and cobalt (2-4%) particles. The use of DU and HMTAs in military munitions could result in their internalization in humans. Limited data exist however, regarding the long-term health effects of internalized DU and HMTAs in humans. Both DU and HMTAs possess a tumorigenic transforming potential and are genotoxic and mutagenic in vitro. Using insoluble DU-UO2 and a reconstituted mixture of tungsten, nickel, cobalt (rWNiCo), we tested their ability to induce stress genes in thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG2). The commercially available CAT-Tox (L) cellular assay consists of a panel of cell lines stably transfected with reporter genes consisting of a coding sequence for chloramphenicol acetyl transferase (CAT) under transcriptional control by mammalian stress gene regulatory sequences. DU, (5-50 microg/ml) produced a complex profile of activity demonstrating significant dose-dependent induction of the hMTIIA FOS, p53RE, Gadd153, Gadd45, NFkappaBRE, CRE, HSP70, RARE, and GRP78 promoters. The rWNiCo mixture (5-50 microg/ml) showed dose-related induction of the GSTYA, hMTIIA, p53RE, FOS, NFkappaBRE, HSP70, and CRE promoters. An examination of the pure metals, tungsten (W), nickel (Ni), and cobalt (Co), comprising the rWNiCo mixture, demonstrated that each metal exhibited a similar pattern of gene induction, but at a significantly decreased magnitude than that of the rWNiCo mixture. These data showed a synergistic activation of gene expression by the metals in the rWNiCo mixture. Our data show for the first time that DU and rWNiCo can activate gene expression through several signal transduction pathways that may be involved in the toxicity and tumorigenicity of both DU and HMTAs.

Carcinoma, Hepatocellular↗
PubMed1987

Inhibition of methanogenesis in pure cultures by ammonia, fatty acids, and heavy metals, and protection against heavy metal toxicity by sewage sludge.

The effect of ammonium chloride, sodium butyrate, sodium propionate, and the heavy metals nickel, zinc, and copper on methanogenesis by pure cultures of Methanospirillum hungatei, Methanosarcina barkeri, Methanobacterium thermoautotrophicum, and Methanobacterium formicicum at pH 6.5 was studied. The latter three strains were resistant to greater than 60 g/L of the volatile fatty acids and to greater than 10 g/L of NH3 N. Methanospirillum hungatei was somewhat more sensitive with 50% inhibition of methanogenesis occurring at 4.2 g/L NH3 N, 27 g/L butyrate, and 41 g/L propionate. All strains were very sensitive to both copper (1-5 mg/L) and zinc (1-10 mg/L), but much more resistant to nickel. Zinc and copper concentrations 30 to 270 times higher were required to cause inhibition of Msp. hungatei incubated in sewage sludge compared with buffer, indicating a strong protective environment was afforded the methanogens against heavy metal toxicity in the sludge.

Ammonium Chloride↗
PubMed2004

Heavy metal stabilization in municipal solid waste incineration flyash using heavy metal chelating agents.

Heavy metal chemical stabilization with synthesized heavy metal chelating agent was assessed for flyash from municipal solid waste incinerator. Flyash can contain heavy metals (e.g. Pb, Cd) which can leach. A new kind of heavy metal chelating agent showed more attractive competition than inorganic chemicals in stabilizing flyash. The synthesizing method of this kind of heavy metal chelating agent was explained in this paper, and the technology process and treatment efficiency of the chelating agent in treating flyash were experimentally studied, which was compared with the results of inorganic chemical agents such as sodium sulfide and lime. The heavy metals in flyash were stabilized more effectively by using heavy metal chelating agents than by using sodium sulfide and lime, furthermore, the stabilized products using the chelating agents can meet the landfill disposal controlling standards for heavy metal waste. pH-dependent leaching experiment showed the stabilized flyash by treatment with heavy metal chelating agent could keep long-term stabilization within a broad range of pH value. Thus, the risk of secondary pollution for the stabilized products was reduced dramatically when the environment condition changes during its disposal period.

Carbon↗
PubMed2004

Identification of Thlaspi caerulescens genes that may be involved in heavy metal hyperaccumulation and tolerance. Characterization of a novel heavy metal transporting ATPase.

Thlaspi caerulescens is a heavy metal hyperaccumulator plant species that is able to accumulate extremely high levels of zinc (Zn) and cadmium (Cd) in its shoots (30,000 microg g(-1) Zn and 10,000 microg g(-1) Cd), and has been the subject of intense research as a model plant to gain a better understanding of the mechanisms of heavy metal hyperaccumulation and tolerance and as a source of genes for developing plant species better suited for the phytoremediation of metal-contaminated soils. In this study, we report on the results of a yeast (Saccharomyces cerevisae) complementation screen aimed at identifying candidate heavy metal tolerance genes in T. caerulescens. A number of Thlaspi genes that conferred Cd tolerance to yeast were identified, including possible metal-binding ligands from the metallothionein gene family, and a P-type ATPase that is a member of the P1B subfamily of purported heavy metal-translocating ATPases. A detailed characterization of the Thlaspi heavy metal ATPase, TcHMA4, demonstrated that it mediates yeast metal tolerance via active efflux of a number of different heavy metals (Cd, Zn, lead [Pb], and copper [Cu]) out of the cell. However, in T. caerulescens, based on differences in tissue-specific and metal-responsive expression of this transporter compared with its homolog in Arabidopsis (Arabidopsis thaliana), we suggest that it may not be involved in metal tolerance. Instead, we hypothesize that it may play a role in xylem loading of metals and thus could be a key player in the hyperaccumulation phenotype expressed in T. caerulescens. Additionally, evidence is presented showing that the C terminus of the TcHMA4 protein, which contains numerous possible heavy metal-binding His and Cys repeats residues, participates in heavy metal binding. When partial peptides from this C-terminal domain were expressed in yeast, they conferred an extremely high level of Cd tolerance and Cd hyperaccumulation. The possibilities for enhancing the metal tolerance and phytoremediation potential of higher plants via expression of these metal-binding peptides are also discussed.

Adenosine Triphosphatases↗
PubMed2003

Electrodialytic removal of heavy metals from different fly ashes. Influence of heavy metal speciation in the ashes.

Electrodialytic remediation, an electrochemically assisted extraction method, has recently been suggested as a potential method for removal of heavy metals from fly ashes. In this work, electrodialytic remediation of three different fly ashes, i.e. two municipal solid waste incinerator (MSWI) fly ashes and one wood combustion fly ash was studied in lab scale, and the results were discussed in relation to the expected heavy metal speciation in the ashes. The pH-dependent desorption characteristics for Cr differed between the two MSWI ashes but were similar for Cd, Pb, Zn and Cu. Thus, it was expected that the speciation of Cd, Pb, Zn and Cu was similar in the two ashes. However, in succeeding electrodialytic remediation experiments significant differences in removal efficiencies were observed, especially for Pb and Zn. In analogous electrodialytic remediation experiments, 8% Pb and 73% Zn was removed from one of the MSWI ashes, but only 2.5% Pb and 24% Zn from the other. These differences are probably due to variations in pH and heavy metal speciation between the different ashes. Cd, the sole heavy metal of environmental concern in the wood ash, was found more tightly bonded in this ash than in the two MSWI ashes. Approximately 70% Cd was removed from both types of ashes during 3 weeks of electrodialytic remediation, although the total concentration was a factor of 10 lower in the wood ash. It was suggested that complex Cd-silicates are likely phases in the wood ash whereas more soluble, condensed phases are dominating in the MSWI ashes.

Electrochemistry↗
PubMed1998

Mechanisms of cell activation by heavy metal ions.

Heavy metal ions can be released by corroding metallic implants into the surrounding tissue. When they enter blood vessels some of them are carried by proteins like albumin and can be taken up by endothelial cells lining the vessels. To study their involvement in the inflammatory response we investigated heavy metal ion induced effects in cultured human vascular endothelial cells (HUVECs). NiCl2 and CoCl2 upregulate, especially in concentrations of 1 mM, the expression of adhesion molecules (e.g., E-selectin and intercellular adhesion molecule-1), as well as the cytokines IL-6 and IL-8, as shown by enzyme immunoassay and Northern blot analysis. In addition, possible signal transduction mechanisms were elucidated. The HUVECs were treated with various selective inhibitory drugs followed by the incubation of metal ions before measuring the expression of the above-mentioned endothelial factors. Two protein kinase inhibitors (H-7 and H-8) strongly repressed Ni2+ and Co2+ enhanced expression, as did the phospholipase A2 inhibitor quinacrine. Other selective inhibitors of protein kinases C or A, or cGMP-dependent protein kinases, as well as calcium antagonists like 1,2-bis(2-aminophenoxy)ethan-N,N,N',N'-tetraacetic acid and 3,4,5-trimethoxybenzosaure 8-(diethylamino)-octylester and inhibitors of receptor mediated endocytosis (primary amines), had no influence. We showed that NiCl2 and CoCl2 activate the translocation of the transcription factor nuclear factor (NF)-kappaB into the cell nucleus and enhance its binding to a NF-kappaB consensus sequence as shown by mobility shift analysis. Furthermore, we demonstrated the activation of AP-1. Despite the repression of heavy metal induced adhesion molecule synthesis, we did not detect any inhibition of NF-kappaB translocation by H-7 or H-8. Therefore, it must be concluded that heavy metal ions like Ni2+ and Co2+ activate two or more signal transduction pathways in endothelial cells. We clearly showed that there is one pathway in which H-7 and H-8 sensitive protein kinases are involved and a second pathway leading to NF-kappaB activation, which is insensitive to H-7 and H-8. Our results demonstrate that heavy metal ions induce mechanisms of gene activation in endothelial cells as do proinflammatory mediators, indicating that corroding metal ion containing biomaterials can provoke inflammatory reactions by known, as well as by yet unknown, intracellular signaling pathways.

Base Sequence↗
PubMed2006

Characterization of a novel plant promoter specifically induced by heavy metal and identification of the promoter regions conferring heavy metal responsiveness.

The bean (Phaseolus vulgaris) stress-related gene number 2 (PvSR2) gene responds to heavy metals but not to other forms of environmental stresses. To elucidate its heavy metal-regulatory mechanism at the transcriptional level, we isolated and characterized the promoter region (-1623/+48) of PvSR2. Deletions from the 5' end revealed that a sequence between -222 and -147 relative to the transcriptional start site was sufficient for heavy metal-specific induction of the promoter region of PvSR2. Detailed analysis of this 76-bp fragment indicated that heavy metal-responsive elements were localized in two regions (-222/-188 and -187/-147), each of which could separately confer heavy metal-responsive expression on the beta-glucuronidase gene in the context of a minimal cauliflower mosaic virus 35S promoter. Region I (-222/-188) contains a motif (metal-regulatory element-like sequence) similar to the consensus metal-regulatory element of the animal metallothionein gene, and mutation of this motif eliminated the heavy metal-inducible function of region I. Region II (-187/-147) had no similarity to previously identified cis-acting elements involved in heavy metal induction, suggesting the presence of a novel heavy metal-responsive element. Transformed tobacco (Nicotiana tabacum) seedlings expressing beta-glucuronidase under control of the PvSR2 promoter region (-687/+48) showed heavy metal-specific responsive activity that depended on the type and concentration of the heavy metal and the type of organ. These findings further our understanding of the regulation of PvSR2 expression and provide a new heavy-metal-inducible promoter system in transgenic plants.

Base Sequence↗
PubMed2006

Cloning and expression analysis of SKn-type dehydrin gene from bean in response to heavy metals.

A heavy metal responsive gene PvSR3 (GenBank accession number U54703) encoding an acid dehydrin was isolated from a mercuric chloride-treated bean (Phaseolus vulgaris L.) leaf cDNA library by differential screening using cDNAs derived from treated and untreated plants. The PvSR3 cDNA is 981-bp long and has a 606-bp open-reading frame with a 202-residue-deduced amino acid sequence. The PvSR3 sequence contains two conserved repeats of the characteristic lysine-rich K segment (EKKGIMDKIKEKLPG) preceded by an 8-serine residue stretch, whereas the Y segment (DEYGNP) conserved motif is absent. The deduced protein has a calculated molecular weight of 23 kDa and an isoelectric point of 5.2. Sequence similarity and comparative analysis showed that PvSR3 shares 70 and 73% similarity with the dehydrin of poplar and pepper, respectively. Southern hybridizations indicated that PvSR3 was a low copy-number gene. Northern blot analysis revealed that PvSR3 mRNA was weakly detected in seedling leaves. However, the gene expression was strongly stimulated by heavy metals, such as mercury, cadmium, arsenic, and copper, whereas virus infection and salt had little effect on it. In contrast, PvSR3 was not responsive to drought or abscisic acid (ABA), and was downregulated by UV radiation. Furthermore, PvSR3 was upregulated by the exogenous signaling molecules, including salicylic acid (SA) and hydrogen peroxide (H2O2). It is suggested that PvSR3 is extremely related to heavy metal stress, and might play an important role in metal detoxification and resistance to the damage caused by heavy metals.

Abscisic Acid↗
PubMed1988

Hematologic effects of heavy metal poisoning.

Heavy metal poisoning can cause a variety of hematologic disorders. Exposure to heavy metals is ubiquitous in the industrial environment and must be considered in the differential diagnosis of many types of anemia. The heavy metals most commonly associated with hematologic toxicity are arsenic and its derivative arsine, copper, gold, lead, and zinc. A few distinctive clinical features characterize the hematologic manifestations of many occult heavy metal poisonings. These features have a limited differential diagnosis. A knowledge of these clinical features can assist the astute clinician in making the correct diagnosis.

Anemia↗
PubMed2003

Functional expression of a bacterial heavy metal transporter in Arabidopsis enhances resistance to and decreases uptake of heavy metals.

Large parts of agricultural soil are contaminated with lead (Pb) and cadmium (Cd). Although most environments are not heavily contaminated, the low levels observed nonetheless pose a high risk of heavy metal accumulation in the food chain. Therefore, approaches to develop plants with reduced heavy metal uptake are important. Recently, many transgenic plants with increased heavy metal resistance and uptake of heavy metals were developed for the purpose of phytoremediation. However, to reduce heavy metal in the food chain, plants that transfer less heavy metals to the shoot are required. We tested whether an Escherichia coli gene, ZntA, which encodes a Pb(II)/Cd(II)/Zn(II) pump, could be useful for developing plants with reduced heavy metal content. Yeast cells transformed with this gene had improved resistance to Pb(II) and Cd(II). In Arabidopsis plants transformed with ZntA, ZntA was localized at the plasma membrane and improved the resistance of the plants to Pb(II) and Cd(II). The shoots of the transgenic plants had decreased Pb and Cd content. Moreover, the transgenic protoplasts showed lower accumulation of Cd and faster release of preloaded Cd than wild-type protoplasts. These results show that a bacterial transporter gene, ZntA, can be functionally expressed in plant cells, and that that it may be useful for the development of crop plants that are safe from heavy metal contamination.

Adenosine Triphosphatases↗
PubMed2005

The influence of heavy metals on the production of extracellular polymer substances in the processes of heavy metal ions elimination.

Wastewaters from a chemical industry polluted by heavy metal ions represent a hazard for all living organisms. It can mean danger for ecosystems and human health. New methods are sought alternative to traditional chemical and physical processes. Active elimination process of heavy metals ions provided by living cells, their components and extracellular products represents a potential way of separating toxic heavy metals from industrial wastewaters. While the abilities of bacteria to remove metal ions in solution are extensively used, fungi have been recognized as a promising kind of low-cost adsorbents for removal of heavy-metal ions from aqueous waste sources. Yeasts and fungi differ from each other in their constitution and in their abilities to produce variety of extracellular polymeric substances (EPS) with different mechanisms of metal interactions. The accumulation of Cd(2+), Cr(6+), Pb(2+), Ni(2+) and Zn(2+) by yeasts and their EPS was screened at twelve different yeast species in microcultivation system Bioscreen C and in the shaking Erlenmayer's flasks. This results were compared with the production of yeast EPS and the composition of yeast cell walls. The EPS production was measured during the yeast growth and cell wall composition was studied during the cultivations in the shaking flasks. At the end of the process extracellular polymers and their chemical composition were isolated and amount of bound heavy metals was characterized. The variable composition and the amount of the EPS were found at various yeast strains. It was influenced by various compositions of growth medium and also by various concentrations of heavy metals. It is evident, that the amount of bound heavy metals was different. The work reviews the possibilities of usage of various yeast EPS and components of cell walls in the elimination processes of heavy metal ions. Further the structure and properties of yeasts cell wall and EPS were discussed. The finding of mechanisms mentioned above is necessary to identify the functional groups entered in the metals elimination processes.

Biodegradation, Environmental↗