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1.
Heavy metals are important for various biological systems, but, in excess, they pose a serious risk to human health. Heavy metals are commonly used in consumer and industrial products. Despite the increasing evidence on the adverse effects of heavy metals, the detailed mechanisms underlying their action on lung cancer progression are still poorly understood. In the present study, we investigated whether heavy metals (mercury chloride and lead acetate) affect cell viability, cell cycle, and apoptotic cell death in human lung fibroblast MRC5 cells. The results showed that mercury chloride arrested the sub-G1 and G2/M phases by inducing cyclin B1 expression. In addition, the exposure to mercury chloride increased apoptosis through the activation of caspase-3. However, lead had no cytotoxic effects on human lung fibroblast MRC5 cells at low concentration. These findings demonstrated that mercury chloride affects the cytotoxicity of MRC5 cells by increasing cell cycle progression and apoptotic cell death.  相似文献   

2.
3.
Osteosarcoma (OS) is the most common type of primary bone tumor. Currently, there are limited treatment options for metastatic OS. Alpha-ketoglutarate (AKG), i.e., a multifunctional intermediate of the Krebs cycle, is one of the central metabolic regulators of tumor fate and plays an important role in cancerogenesis and tumor progression. There is growing evidence suggesting that AKG may represent a novel adjuvant therapeutic opportunity in anti-cancer therapy. The present study was intended to check whether supplementation of Saos-2 and HOS osteosarcoma cell lines (harboring a TP53 mutation) with exogenous AKG exerted an anti-cancer effect. The results revealed that AKG inhibited the proliferation of both OS cell lines in a concentration-dependent manner. As evidenced by flow cytometry, AKG blocked cell cycle progression at the G1 stage in both cell lines, which was accompanied by a decreased level of cyclin D1 in HOS and increased expression of p21Waf1/Cip1 protein in Saos-2 cells (evaluated with the ELISA method). Moreover, AKG induced apoptotic cell death and caspase-3 activation in both OS cell lines (determined by cytometric analysis). Both the immunoblotting and cytometric analysis revealed that the AKG-induced apoptosis proceeded predominantly through activation of an intrinsic caspase 9-dependent apoptotic pathway and an increased Bax/Bcl-2 ratio. The apoptotic process in the AKG-treated cells was mediated via c-Jun N-terminal protein kinase (JNK) activation, as the specific inhibitor of this kinase partially rescued the cells from apoptotic death. In addition, the AKG treatment led to reduced activation of extracellular signal-regulated kinase (ERK1/2) and significant inhibition of cell migration and invasion in vitro concomitantly with decreased production of pro-metastatic transforming growth factor β (TGF-β) and pro-angiogenic vascular endothelial growth factor (VEGF) in both OS cell lines suggesting the anti-metastatic potential of this compound. In conclusion, we showed the anti-osteosarcoma potential of AKG and provided a rationale for a further study of the possible application of AKG in OS therapy.  相似文献   

4.
Obesity-related neurodegenerative diseases are associated with elevated saturated fatty acids (SFAs) in the brain. An increase in SFAs, especially palmitic acid (PA), triggers neuron cell apoptosis, causing cognitive function to deteriorate. In the present study, we focused on the specific mechanism by which PA triggers SH-SY5Y neuron cell apoptosis. We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells. Our data further showed that G2/M arrest is involved in elevation of endoplasmic reticular (ER) stress according to an increase in p-eukaryotic translation inhibition factor 2α, an ER stress marker. Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer’s disease. Interestingly, SFA-induced ER stress, G2/M arrest and cell apoptosis were reversed by treatment with 2-bromopalmitate, a protein palmitoylation inhibitor. These findings suggest that protein palmitoylation plays a crucial role in SFA-induced neuron cell cycle G2/M arrest, ER stress and apoptosis; this provides a novel strategy for preventing SFA-induced neuron cell dysfunction.  相似文献   

5.
6.
Mercury ranks third on the U.S. Agency of Toxic Substances and Disease Registry priority list of hazardous substances, behind only arsenic and lead. We have undertaken uncovering the mechanisms underlying the developmental toxicity of methylmercury (MeHg), inorganic mercury (HgCl2), lead acetate (Pb), and sodium arsenite (As). To probe these differences, we used the Drosophila model, taking advantage of three developmental transitions—pupariation, metamorphosis, and eclosion—to differentiate potentially unique windows of toxicity. We elaborated dose response profiles for each individual metal administered in food and accounted for internal body burden, also extending analyses to evaluate combinatorial metal mixture effects. We observed all four metals producing larval lethality and delayed pupariation, with MeHg being most potent. Compared to other metals, MeHg’s potency is caused by a higher body burden with respect to dose. MeHg uniquely caused dose-dependent failure in eclosion that was unexpectedly rescued by titrating in HgCl2. Our results highlight a unique developmental window and toxicokinetic properties where MeHg acts with specificity relative to HgCl2, Pb, and As. These findings will serve to refine future studies aimed at revealing tissue morphogenesis events and cell signaling pathways, potentially conserved in higher organisms, that selectively mediate MeHg toxicity and its antagonism by HgCl2.  相似文献   

7.
The removal of inorganic mercury from waste water streams arising from mines, using an artificial amorphous compound of the crandallite type synthesized in our laboratory, Ca0.5Sr0.5Al3(OH)6(HPO4) (PO4), has been investigated. This compound exhibits an extremely wide range of ionic substitutions: Ca2+ and Sr2+ were interchanged with Hg2+, so the mercury content of the waste water, ranging from 70 to 90 ppm, was reduced to less than 0.1 ppm. The process has been studied under batch conditions. The crandallite showed a high capacity for the exchange of mercury from mercuric nitrate solutions, 1.555 meq g?1. The ion‐exchange equilibrium isotherms for Hg2+ were correlated by the Langmuir equation. The recovery of mercury from Hg‐crandallite using HCl solutions and thermal treatment was also studied. Optimum recuperation of mercury is achieved by chemical reaction with HCl solution (pH 2.25). At these conditions, 75% of the mercury is recovered as the HgCl42? complex in a simple batch process, and the crandallite (in the protonic form) can be reused. © 2003 Society of Chemical Industry  相似文献   

8.
《分离科学与技术》2012,47(8):809-821
Abstract

The separation of mercury from aqueous HgCl2 solutions by onion skins (outermost coat) was studied both experimentally and theoretically. The distribution equilibria were measured by the batchwise method. The experimental results revealed that onion skin is a useful material for separating mercury from aqueous systems. The distribution data obtained at 25°C were analyzed by using the theory based on the law of mass action. The separation of dissolved mercury by onion skins was found to be a process accompanied by an ion-exchange reaction of the cationic complex HgCl+ and an adsorption of the neutral complex HgCl2. The equilibrium constants of the ion-exchange and adsorption processes at 25°C and the mercury-binding capacity of onion skins were determined. Further, it was found that the distribution equilibrium of mercury is comparatively insensitive to temperature.  相似文献   

9.
Pan Guo  Chu-guang Zheng 《Fuel》2011,90(5):1840-1846
First-principle calculations based on Density Functional Theory were performed to investigate the binding mechanisms of mercury species on α-Fe2O3 (0 0 1) surface. This is crucial in demonstrating the contribution of α-Fe2O3 existing in fly ash for mercury removal. It has been determined that Hg0 is adsorbed on the α-Fe2O3 (0 0 1) surface with physisorption mechanism. The oxidized forms of HgCl and HgCl2 can be adsorbed on α-Fe2O3 (0 0 1) dissociatively or non-dissociatively. In the case of dissociative adsorption, a close examination of the energy diagram indicates that HgCl may be favorable for the adsorption of Cl and desorption of Hg. The dissociation of HgCl2 with the binding of Cl and HgCl on the surface is possibly the dominant interaction pathway.  相似文献   

10.
Although the lignan compound fargesin is a major ingredient in Shin-Yi, the roles of fargesin in carcinogenesis and cancer cell growth have not been elucidated. In this study, we observed that fargesin inhibited cell proliferation and transformation by suppression of epidermal growth factor (EGF)-stimulated G1/S-phase cell cycle transition in premalignant JB6 Cl41 and HaCaT cells. Unexpectedly, we found that signaling pathway analyses showed different regulation patterns in which fargesin inhibited phosphatidylinositol 3-kinase/AKT signaling without an alteration of or increase in mitogen activated protein kinase (MAPK) in JB6 Cl41 and HaCaT cells, while both signaling pathways were abrogated by fargesin treatment in colon cancer cells. We further found that fargesin-induced colony growth inhibition of colon cancer cells was mediated by suppression of the cyclin dependent kinase 2 (CDK2)/cyclin E signaling axis by upregulation of p21WAF1/Cip1, resulting in G1-phase cell cycle accumulation in a dose-dependent manner. Simultaneously, the suppression of CDK2/cyclin E and induction of p21WAF1/Cip1 were correlated with Rb phosphorylation and c-Myc suppression. Taken together, we conclude that fargesin-mediated c-Myc suppression inhibits EGF-induced cell transformation and colon cancer cell colony growth by the suppression of retinoblastoma (Rb)-E2F and CDK/cyclin signaling pathways, which are mainly regulated by MAPK and PKB signaling pathways.  相似文献   

11.
ABSTRACT

Mercury extraction from acidic aqueous solutions by the TRUEX process solvent, 0.2 M n-octyl(phenyl)N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO), 1.4 M tributylphosphate (TBP) in n-dodecane, has not been extensively examined, Research is currently in progress at the Idaho Chemical Processing Plant to evaluate the TRUEX process for actinide removal from several acidic waste streams, including liquid sodium-bearing waste (SBW), which contains significant quantities of mercury. Reactions for two mercury species, HgCl2 and HgCl4 ?2, are reported. Classical slope analysis techniques were utilized to evaluate the stoichiometric coefficients of each Hg species independently for both CMPO and TBP. The slope analysis results indicate that even the HgCl4 ?2 species extracts as HgCl2. The results also indicate that 1.9 to 2.2 moles of CMPO and 1.5 to 1.81 moles of TBP are required per mole of HgCl2 extracted. A generic equation for mercury extraction into CMPO or TBP has been shown to be:

where x = 2 or 4, y = 0 or ?2, E = CMPO or TBP, a = the experimentally determined CMPO or TBP stoichiometry, and over lines indicate organic species. Equilibrium constants for HgCl2 species were determined to be 295 when extracted by CMPO and 18.2 when extracted by TBP. Equilibrium constants for the HgCl4 ?2 species were found to range between 5.8 and 12.0 for the CMPO reaction and 0.13 to 0.27 with TBP.  相似文献   

12.
Understanding mercury binding on activated carbon   总被引:1,自引:0,他引:1  
Bihter Padak 《Carbon》2009,47(12):2855-2864
Understanding the mechanism by which mercury adsorbs on activated carbon is crucial to the design and fabrication of effective capture technologies. In this study, the possible binding mechanism of mercury (Hg) and its species, i.e., HgCl and HgCl2 on activated carbon is investigated using ab initio-based energetic calculations. The activated carbon surface is modeled by a single graphene layer in which the edge atoms on the upper side are unsaturated in order to simulate the active sites. In some cases, chlorine atoms are placed at the edge sites to examine the effect of chlorine on the binding of Hg, HgCl and HgCl2. It has been concluded that both HgCl and HgCl2 can be adsorbed dissociatively or non-dissociatively. In the case of dissociative adsorption, it is energetically favorable for atomic Hg to desorb and energetically favorable for it to remain on the surface in the Hg1+ state, HgCl. The Hg2+ oxidized compound, HgCl2 was not found to be stable on the surface. The most probable mercury species on the surface was found to be HgCl.  相似文献   

13.
A series of benzo[b]furans was synthesized with modification at the 5‐position of the benzene ring by introducing C‐linked substituents (aryl, alkenyl, alkynyl, etc.). These compounds were evaluated for their antiproliferative activities, inhibition of tubulin polymerization, and cell‐cycle effects. Some compounds in this series displayed excellent activity in the nanomolar range against lung cancer (A549) and renal cell carcinoma (ACHN) cancer cell lines. (6‐Methoxy‐5‐((4‐methoxyphenyl)ethynyl)‐3‐methylbenzofuran‐2‐yl)(3,4,5‐trimethoxyphenyl)methanone ( 26 ) and (E)‐3‐(6‐methoxy‐3‐methyl‐2‐(1‐(3,4,5‐trimethoxyphenyl)vinyl)benzofuran‐5‐yl)prop‐2‐en‐1‐ol ( 36 ) showed significant activity in the A549 cell line, with IC50 values of 0.08 and 0.06 μM , respectively. G2/M cell‐cycle arrest and subsequent apoptosis was observed in the A549 cell line after treatment with these compounds. The most active compound in this series, 36 , also inhibited tubulin polymerization with a value similar to that of combretastatin A‐4 (1.95 and 1.86 μM , respectively). Furthermore, detailed biological studies such as Hoechst 33258 staining, DNA fragmentation and caspase‐3 assays, and western blot analyses with the pro‐apoptotic protein Bax and the anti‐apoptotic protein Bcl‐2 also suggested that these compounds induce cell death by apoptosis. Molecular docking studies indicated that compound 36 interacts and binds efficiently with the tubulin protein.  相似文献   

14.
Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G2/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5′ AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells.  相似文献   

15.
Mercury emissions from coal-fired power plants account for 40% of the anthropogenic mercury emissions in the U.S. The speciation of mercury largely determines the amount of mercury capture in control equipments. Conversion of insoluble Hg0 into more soluble Hg2+ facilitates its removal in scrubbers. Past studies suggest that an added supply of OH radicals possibly enhance the mercury oxidation process. This study demonstrates that the application of H2O2, as source of OH radicals, accelerates the oxidation of Hg0 into Hg2+. A detailed kinetic reaction mechanism was compiled and the reaction pathways were established to analyze the effect of H2O2 addition. The optimum temperature range for the oxidation was 480–490 °C. The sensitivity analysis of the reaction mechanism indicates that the supply OH radicals increase the formation of atomic Cl, which accelerates the formation of HgCl2 enhancing the oxidation process. Also, the pathway through HOCl radical, generated by the interactions between chlorine and H2O2 was prominent in the oxidation of Hg0. The flue gas NO was found to be inhibiting the Hg0 oxidation, since it competed for the supplied H2O2. Studying the interactions with the other flue gas components and the surface chemistry with particles in the flue gas could be important and may improve the insight into the post combustion transformation of mercury in a comprehensive way.  相似文献   

16.
Here, we report a natural chemical Matrine, which exhibits anti-melanoma potential with its PTEN activation mechanism. Matrine effectively inhibited proliferation of several carcinoma cell lines, including melanoma V600EBRAF harboring M21 cells. Flow cytometry analysis showed Matrine induced G0/G1 cell cycle arrest in M21 cells dose-dependently. Apoptosis in M21 cells induced by Matrine was identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis and Annexin-V/FITC staining. Molecular mechanistic study suggested that Matrine upregulated both mRNA level and protein expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN), leading to inhibition of the PI3K/Akt pathway. Downregulation of phosphor-Aktser473 by Matrine activated p21 and Bax, which contributed to G0/G1 cell cycle and apoptosis. Besides, Matrine enhanced the PI3K/Akt inhibition effects to inhibit the cell proliferation with PI3K inhibitor, LY2940002. In summary, our findings suggest Matrine is a promising antitumor drug candidate with its possible PTEN activation mechanisms for treating cancer diseases, such as melanomas.  相似文献   

17.

Background

Increasing environmental and occupational exposures to nanoparticles (NPs) warrant deeper insight into the toxicological mechanisms induced by these materials. The present study was designed to characterize the cell death induced by carbon black (CB) and titanium dioxide (TiO2) NPs in bronchial epithelial cells (16HBE14o- cell line and primary cells) and to investigate the implicated molecular pathways.

Results

Detailed time course studies revealed that both CB (13 nm) and TiO2(15 nm) NP exposed cells exhibit typical morphological (decreased cell size, membrane blebbing, peripheral chromatin condensation, apoptotic body formation) and biochemical (caspase activation and DNA fragmentation) features of apoptotic cell death. A decrease in mitochondrial membrane potential, activation of Bax and release of cytochrome c from mitochondria were only observed in case of CB NPs whereas lipid peroxidation, lysosomal membrane destabilization and cathepsin B release were observed during the apoptotic process induced by TiO2 NPs. Furthermore, ROS production was observed after exposure to CB and TiO2 but hydrogen peroxide (H2O2) production was only involved in apoptosis induction by CB NPs.

Conclusions

Both CB and TiO2 NPs induce apoptotic cell death in bronchial epithelial cells. CB NPs induce apoptosis by a ROS dependent mitochondrial pathway whereas TiO2 NPs induce cell death through lysosomal membrane destabilization and lipid peroxidation. Although the final outcome is similar (apoptosis), the molecular pathways activated by NPs differ depending upon the chemical nature of the NPs.  相似文献   

18.
The synthesis of hybrid organic–inorganic polymers by combination of mercury(II) halides with the ligand 1,5-bis(isonicotinamido)naphthalene, C10H6(NHCO-4-C5H4N)2, 1. The compounds of formula [HgX2(1)] form either linear (X = Cl, Br) or zig-zag (X = I) polymers and contain tetrahedral mercury(II) centers with bridging ligands 1. The polymers are further assembled by hydrogen bonding between amide groups. When X = Cl or Br, two-dimensional sheet structures are formed whereas, when X = I, a three-dimensional network is formed. A new polymeric form of [HgCl2(Me2SO)] is also described. Dedicated to Ian Manners for his pioneering research on organometallic polymers  相似文献   

19.
Tube-like HgS nanoparticles with face center cubic structure were synthesized via employing TM01-type microwave irradiation as template. In this process, HgCl2 and Na2S were used as mercury and sulfur sources, respectively, which changed to HgS through chemical reaction in aqueous solution and under ambient condition. The products were investigated with X-ray diffraction and transmission electron microscope.  相似文献   

20.
Activated char obtained by the co-pyrolysis of a mixture of lignite and biomass impregnated with ZnCl2 solution was found to be effective for the high-temperature capture of mercury from syngas. The prepared samples were characterized by X-ray photoelectron spectroscopy, Hg-thermal programmed desorption as well as Brunauer- Emmett-Teller analysis. The results show that activated char exhibits a large surface area as well as abundant micropores and C-Cl, C=O, and COOH functional groups. During the chemisorption of mercury, gaseous Hg0 is first oxidized by C-Cl to HgCl2; HgCl2 which acts as the intermediate product then reacts with the C=O and COOH functional groups on the surface of activated char to generate Hg-OM. At high adsorption temperatures, Hg-OM on the adsorbent surface can further decompose and generate HgO. The C-Cl group is important for the first oxidation step of gaseous Hg0, and the formation of HgCl2 is the rate-determining step for the entire process of adsorption.  相似文献   

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