DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, Ryan L.; Galaleldeen, Ahmad; Villarreal, Johanna

In eukaryotes the bimetallic Cu/Zn superoxide dismutase (SOD) enzymes play important roles in the biology of reactive oxygen species by disproportionating superoxide anion. We reported that the fungal pathogen Candida albicans expresses a novel copper-only SOD, known as SOD5, that lacks the zinc cofactor and electrostatic loop (ESL) domain of Cu/Zn-SODs for substrate guidance. In spite of these abnormalities, C. albicans SOD5 can disproportionate superoxide at rates limited only by diffusion. Here we demonstrate that this curious copper-only SOD occurs throughout the fungal kingdom as well as in phylogenetically distant oomycetes or “pseudofungi” species. It is the only form ofmore » extracellular SOD in fungi and oomycetes, in stark contrast to the extracellular Cu/Zn-SODs of plants and animals. Through structural biology and biochemical approaches we demonstrate that these copper-only SODs have evolved with a specialized active site consisting of two highly conserved residues equivalent to SOD5 Glu-110 and Asp-113. The equivalent positions are zinc binding ligands in Cu/Zn-SODs and have evolved in copper-only SODs to control catalysis and copper binding in lieu of zinc and the ESL. Similar to the zinc ion in Cu/Zn-SODs, SOD5 Glu-110 helps orient a key copper-coordinating histidine and extends the pH range of enzyme catalysis. Furthermore, SOD5 Asp-113 connects to the active site in a manner similar to that of the ESL in Cu/Zn-SODs and assists in copper cofactor binding. Copper-only SODs are virulence factors for certain fungal pathogens; thus this unique active site may be a target for future anti-fungal strategies.« less

Identification of novel superoxide dismutase isoenzymes in the olive (Olea europaea L.) pollen.

PubMed

Zafra, Adoración; Castro, Antonio Jesús; Alché, Juan de Dios

2018-06-08

Among antioxidant enzymes, the superoxide dismutase (SOD) family is a major actor in catalysing the disproportionation of superoxide. Apart from its role as antioxidant, these enzymes have a role in cell signalling, and Cu,Zn-SOD proteins are also major pollen allergens. In order to deepen our understanding of the SOD isoenzymes present in olive pollen and to analyse the molecular variability of the pollen Cu,Zn-SOD family, we carried out biochemical, transcriptomic and localization studies of pollen grains from different olive cultivars and other allergenic species. Olive pollen showed a high rate of total SOD activity in all cultivars assayed, which did not correlate with pollen viability. Mass spectrometry analysis together with activity assays and Western blotting experiments enabled us to identify new forms of Cu,Zn-SOD enzyme (including chloroplastidic and peroxisomal forms) as well as differentially expressed Mn-, Fe- and Cu,Zn-SOD isoenzymes among the pollen of different olive cultivars and allergenic species. Ultrastructural localization of Cu,Zn-SOD revealed its plastidial localization in the pollen grain. We also identified the occurrence of a shorter form of one of the cytosolic Cu,Zn-SOD enzymes, likely as the result of alternative splicing. This shorter enzyme showed lower SOD activity as compared to the full length form. The presence of multiple SOD isoenzymes in the olive pollen could be related to the need of finely tuning the ROS metabolism during the transition from its quiescent condition at maturity to a highly metabolically active state at germination.

Protective effect of human recombinant copper-zinc superoxide dismutase on zone of stasis survival in burns in rats.

PubMed

Shalom, Avshalom; Kramer, Eyal; Westreich, Melvyn

2011-06-01

Superoxide dismutase, acting as a scavenger of oxygen free radicals, has shown mixed results in increasing burn wound survival. Originally, we demonstrated that human recombinant copper-zinc superoxide dismutase (Hr-CuZnSOD) could increase the survival of failing ischemic flaps in a rat model. Because of the possible similar pathophysiology of tissue ischemia in flaps and the zone of stasis in burns, we conducted a later study using 2 groups of rats with standardized intermediate burns, to ascertain whether Hr-CuZnSOD could increase zone of stasis survival in rats. The results showed that postburn Hr-CuZnSOD failed to improve zone of stasis survival in burns. We decided to undertake a new controlled study to ascertain whether there is a protective effect of Hr-CuZnSOD in cases of intermediate burns. We used 2 groups of rats, one of which received prophylactic treatments with Hr-CuZnSOD before the induction of standardized intermediate burns. Results showed that preburn Hr-CuZnSOD also failed to improve zone of stasis survival in burns. Further studies are needed to adequately understand the effect of oxygen free radicals in burn wound pathophysiology and to determine whether Hr-CuZnSOD has a role in the clinical management of burns or should be abandoned.

The effect of nano-TiO2 photocatalysis on the antioxidant activities of Cu, Zn-SOD at physiological pH.

PubMed

Zheng, Wen; Zou, Hai-Feng; Lv, Shao-Wu; Lin, Yan-Hong; Wang, Min; Yan, Fei; Sheng, Ye; Song, Yan-Hua; Chen, Jie; Zheng, Ke-Yan

2017-09-01

Security issues of nanoparticles on biological toxicity and potential environmental risk have attracted more and more attention with the rapid development and wide applications of nanotechnology. In this work, we explored the effect and probable mechanism of nano-TiO 2 on antioxidant activity of copper, zinc superoxide dismutase (Cu, Zn-SOD) under natural light and mixed light at physiological pH. Nano-TiO 2 was prepared by sol-hydrothermal method, and then characterized by X-ray Diffraction (XRD) and Transmission electron micrographs (TEM). The Cu, Zn-SOD was purified by sephadex G75 chromatography and qualitatively analyzed by sodium dodecyl sulfate polypropylene amide gel electrophoresis (SDS-PAGE). The effect and mechanism were elucidated base on Fourier Transform Infrared Spectrometer (FT-IR), Circular Dichroism (CD), zeta potential, and electron spin resonance (ESR) methods. Accompanying the results of FT-IR, CD and zeta potential, it could be concluded that nano-TiO 2 had no effect on the antioxidant activity of Cu, Zn-SOD by comparing the relative activity under natural light at physiological pH. But the relative activity of Cu, Zn-SOD significantly decreased along with the increase of nano-TiO 2 concentration under the mixed light. The results of ESR showed the cause of this phenomenon was the Cu(II) in the active site of Cu, Zn-SOD was reduced to Cu(I) by H 2 O 2 and decreased the content of active Cu, Zn-SOD. The reduction can be inhibited by catalase. Excess O 2 ·- produced by nano-TiO 2 photocatalysis under mixed light accumulated a mass of H 2 O 2 through disproportionation reaction in this experimental condition. The results show that nano-TiO 2 cannot affect the antioxidant activity of Cu, Zn-SOD in daily life. The study on the effect of nano-TiO 2 on Cu, Zn-SOD will provide a valid theory support for biological safety and the toxicological effect mechanism of nanomaterials on enzyme. Copyright © 2017 Elsevier B.V. All rights reserved.

Nucleotide sequence of a complementary DNA encoding pea cytosolic copper/zinc superoxide dismutase. [Pisum sativum L

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, D.A.; Zilinskas, B.A.

1991-08-01

The authors now report the nucleotide sequence of the cytosolic Cu/Zn SOD cloned from a {lambda}gt11 cDNA library constructed from mRNA extracted from leaves of 7- to 10-d pea seedlings (Pisum sativum L.). The clone was isolated using a 22-base synthetic oligonucleotide complementary to the amino acid sequence CGIIGLQG. This sequence, found at the protein's carboxy terminus, is highly conserved among plant cytosolic Cu/Zn SODs but not chloroplastic Cu/Zn SODs. The 738-base pair sequence contains an open reading frame specifying 152 codons and a predicted M{sub r} of 18,024 D. The deduced amino acid sequence is highly homologous (79-82% identity)more » with the sequences of other known plant cytosolic Cu/Zn SODs but less highly conserved (63-65%) when compared with several chloroplastic Cu/Zn SODs including pea (10).« less

Parasitization by Scleroderma guani influences expression of superoxide dismutase genes in Tenebrio molitor

USDA-ARS?s Scientific Manuscript database

Superoxide dismutase (SOD) is an antioxidant enzyme involved in detoxifying reactive oxygen species. In this study, we identified genes encoding the extracellular and intracellular copper-zinc SODs (ecCuZnSOD and icCuZnSOD) and a manganese SOD (MnSOD) in the yellow mealworm beetle, Tenebrio molitor....

Isolation, Chromosomal Localization, and Differential Expression of Mitochondrial Manganese Superoxide Dismutase and Chloroplastic Copper/Zinc Superoxide Dismutase Genes in Wheat1

PubMed Central

Wu, Guohai; Wilen, Ronald W.; Robertson, Albert J.; Gusta, Lawrence V.

1999-01-01

Superoxide dismutase (SOD) gene expression was investigated to elucidate its role in drought and freezing tolerance in spring and winter wheat (Triticum aestivum). cDNAs encoding chloroplastic Cu/ZnSODs and mitochondrial MnSODs were isolated from wheat. MnSOD and Cu/ZnSOD genes were mapped to the long arms of the homologous group-2 and -7 chromosomes, respectively. Northern blots indicated that MnSOD genes were drought inducible and decreased after rehydration. In contrast, Cu/ZnSOD mRNA was not drought inducible but increased after rehydration. In both spring and winter wheat seedlings exposed to 2°C, MnSOD transcripts attained maximum levels between 7 and 49 d. Transcripts of Cu/ZnSOD mRNA were detected sooner in winter than in spring wheat; however, they disappeared after 21 d of acclimation. Transcripts of both classes of SOD genes increased during natural acclimation in both spring and winter types. Exposure of fully hardened plants to three nonlethal freeze-thaw cycles resulted in Cu/Zn mRNA accumulation; however, MnSOD mRNA levels declined in spring wheat but remained unchanged in winter wheat. The results of the dehydration and freeze-thaw-cycle experiments suggest that winter wheat has evolved a more effective stress-repair mechanism than spring wheat. PMID:10364402

Immunolocalization of antioxidant enzymes in high-pressure frozen root and stem nodules of Sesbania rostrata.

PubMed

Rubio, Maria C; Becana, Manuel; Kanematsu, Sumio; Ushimaru, Takashi; James, Euan K

2009-01-01

The activities and localizations of superoxide dismutases (SODs) were compared in root and stem nodules of the semi-aquatic legume Sesbania rostrata using gel-activity assays and immunogold labelling, respectively. Nodules were fixed by high-pressure freezing and dehydrated by freeze substitution. Stem nodules showed more total and specific SOD activities than root nodules because of the presence of chloroplastic CuZnSOD. Most of the total SOD activity of stem and root nodules resulted from 'cytosolic' CuZnSOD, localized in the cytoplasm and chromatin, and from MnSOD in the bacteroids and in the mitochondria of vascular tissue. FeSOD was present in nodule plastids and in leaf chloroplasts, and was found to be associated with chromatin. Superoxide production was detected histochemically in the vascular bundles and in the infected tissue of stem and root nodules, whereas peroxide accumulation was observed in the cortical cell walls and intercellular spaces, as well as within the infection threads of both nodule types. These data suggest a role of CuZnSOD and FeSOD in protecting nuclear DNA from reactive oxygen species and/or in modulating gene activity. The enhanced levels of CuZnSOD, MnSOD and superoxide production in vascular bundle cells are consistent with a role of CuZnSOD and superoxide in the lignification of xylem vessels, but also suggest additional functions in coping with superoxide production by the high respiratory activity of parenchyma cells.

Adaptation to chronic MG132 reduces oxidative toxicity by a CuZnSOD-dependent mechanism

PubMed Central

Leak, Rehana K.; Zigmond, Michael J.; Liou, Anthony K. F.

2010-01-01

To study whether and how cells adapt to chronic cellular stress, we exposed PC12 cells to the proteasome inhibitor MG132 (0.1 μM) for 2 weeks and longer. This treatment reduced chymotrypsin-like proteasome activity by 47% and was associated with protection against both 6-hydroxydopamine (6-OHDA, 100 μM) and higher dose MG132 (40 μM). Protection developed slowly over the course of the first 2 weeks of exposure and was chronic thereafter. There was no change in total glutathione levels after MG132. Buthionine sulfoximine (100 μM) reduced glutathione levels by 60%, but exacerbated 6-OHDA toxicity to the same extent in both MG132-treated and control cells and failed to reduce MG132-induced protection. Chronic MG132 resulted in elevated antioxidant proteins CuZn superoxide dismutase (SOD, +55%), MnSOD (+21%), and catalase (+15%), as well as chaperone heat shock protein 70 (+42%). Examination of SOD enzyme activity revealed higher levels of CuZnSOD (+40%), with no change in MnSOD. We further assessed the mechanism of protection by reducing CuZnSOD levels with two independent siRNA sequences, both of which successfully attenuated protection against 6-OHDA. Previous reports suggested that artificial overexpression of CuZnSOD in dopaminergic cells is protective. Our data complement such observations, revealing that dopaminergic cells are also able to use endogenous CuZnSOD in self-defensive adaptations to chronic stress, and that they can even do so in the face of extensive glutathione loss. PMID:18466318

[Cu,Zn]-Superoxide Dismutase Mutants of the Swine Pathogen Actinobacillus pleuropneumoniae Are Unattenuated in Infections of the Natural Host

PubMed Central

Sheehan, Brian J.; Langford, Paul R.; Rycroft, Andrew N.; Kroll, J. Simon

2000-01-01

Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, contains a periplasmic Cu- and Zn-cofactored superoxide dismutase ([Cu,Zn]-SOD, or SodC) which has the potential, realized in other pathogens, to promote bacterial survival during infection by dismutating host-defense-derived superoxide. Here we describe the construction of a site-specific, [Cu,Zn]-SOD-deficient A. pleuropneumoniae serotype 1 mutant and show that although the mutant is highly sensitive to the microbicidal action of superoxide in vitro, it remains fully virulent in experimental pulmonary infection in pigs. PMID:10899887

The activity of superoxide dismutases (SODs) at the early stages of wheat deetiolation

PubMed Central

Zimak-Piekarczyk, Paulina; Ślesak, Ireneusz

2018-01-01

Unbound tetrapyrroles, i.e. protochlorophyllide (Pchlide), chlorophyllide and chlorophylls, bring the risk of reactive oxygen species (ROS) being generated in the initial stages of angiosperm deetiolation due to inefficient usage of the excitation energy for photosynthetic photochemistry. We analyzed the activity of superoxide dismutases (SODs) in etiolated wheat (Triticum aestivum) leaves and at the beginning of their deetiolation. Mn-SOD and three isoforms of Cu/Zn-SODs were identified both in etiolated and greening leaves of T. aestivum. Two Cu/Zn-SODs, denoted as II and III, were found in plastids. The activity of plastidic Cu/Zn-SOD isoforms as well as that of Mn-SOD correlated with cell aging along a monocot leaf, being the highest at leaf tips. Moreover, a high Pchlide content at leaf tips was observed. No correlation between SOD activity and the accumulation of photoactive Pchlide, i.e. Pchlide bound into ternary Pchlide:Pchlide oxidoreductase:NADPH complexes was found. Cu/Zn-SOD I showed the highest activity at the leaf base. A flash of light induced photoreduction of the photoactive Pchlide to chlorophyllide as well as an increase in all the SODs activity which occurred in a minute time-scale. In the case of seedlings that were deetiolated under continuous light of moderate intensity (100 μmol photons m-2 s-1), only some fluctuations in plastidic Cu/Zn-SODs and Mn-SOD within the first four hours of greening were noticed. The activity of SODs is discussed with respect to the assembly of tetrapyrroles within pigment-protein complexes, monitored by fluorescence spectroscopy at 77 K. PMID:29558520

Parasitization by Scleroderma guani influences expression of superoxide dismutase genes in Tenebrio molitor.

PubMed

Zhu, Jia-Ying; Ze, Sang-Zi; Stanley, David W; Yang, Bin

2014-09-01

Superoxide dismutase (SOD) is an antioxidant enzyme involved in detoxifying reactive oxygen species. In this study, we identified genes encoding the extracellular and intracellular copper-zinc SODs (ecCuZnSOD and icCuZnSOD) and a manganese SOD (MnSOD) in the yellow mealworm beetle, Tenebrio molitor. The cDNAs for ecCuZnSOD, icCuZnSOD, and MnSOD, respectively, encode 24.55, 15.81, and 23.14 kDa polypeptides, which possess structural features typical of other insect SODs. They showed 20-94% identity to other known SOD sequences from Bombyx mori, Musca domestica, Nasonia vitripennis, Pediculus humanus corporis, and Tribolium castaneum. Expression of these genes was analyzed in selected tissues and developmental stages, and following exposure to Escherichia coli and parasitization by Scleroderma guani. We recorded expression of all three SODs in cuticle, fat body, and hemocytes and in the major developmental stages. Relatively higher expressions were detected in late-instar larvae and pupae, compared to other developmental stages. Transcriptional levels were upregulated following bacterial infection. Analysis of pupae parasitized by S. guani revealed that expression of T. molitor SOD genes was significantly induced following parasitization. We infer that these genes act in immune response and in host-parasitoid interactions. © 2014 Wiley Periodicals, Inc.

A novel polymeric ionic liquid-coated magnetic multiwalled carbon nanotubes for the solid-phase extraction of Cu, Zn-superoxide dismutase.

PubMed

Wen, Qian; Wang, Yuzhi; Xu, Kaijia; Li, Na; Zhang, Hongmei; Yang, Qin

2016-10-05

A novel magnetic adsorbent, benzyl groups functionalized imidazolium-based polymeric ionic liquid (PIL)-coated magnetic multiwalled carbon nanotubes (MWCNTs) (m-MWCNTs@PIL), has been successfully synthesized and applied for the extraction of Cu, Zn-superoxide dismutase (Cu, Zn-SOD). The m-MWCNTs@PIL were characterized by X-ray diffraction (XRD), Fourier transform infrared spectrometry (FT-IR), thermal gravimetric analysis (TGA), field emission scanning electron microscopy (FESEM), vibrating sample magnetometer (VSM) and zeta-potential nanoparticles. In this method, the m-MWCNTs@PIL could interact with Cu, Zn-SOD through hydrogen bonding, π-π and electrostatic interactions. The extraction performance of the m-MWCNTs@PIL in the magnetic solid-phase extraction (MSPE) procedure was investigated, coupled with the determination by UV-vis spectrophotometer. Compared with m-MWCNTs@IL and m-MWCNTs, the m-MWCNTs@PIL exhibited the highest extraction capacity of 29.1 mg/g for Cu, Zn-SOD. The adsorbed Cu, Zn-SOD remained high specific activity after being eluted from m-MWCNTs@PIL by 1 moL/L NaCl solution. Besides, the m-MWCNTs@PIL could be easily recycled and successfully employed in the extraction of Cu, Zn-SOD from real samples. Under the optimal conditions, the precision, repeatability and stability of the proposed method were investigated and the RSDs were 0.29%, 1.68% and 0.54%, respectively. Recoveries were in the range of 82.7-102.3%, with the RSD between 3.47% and 5.35%. On the basis of these results, the developed method has great potential in the extraction of Cu, Zn-SOD or other analytes from biological samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Differential expression of copper-zinc superoxide dismutase gene of Polygonum sibiricum leaves, stems and underground stems, subjected to high-salt stress.

PubMed

Qu, Chun-Pu; Xu, Zhi-Ru; Liu, Guan-Jun; Liu, Chun; Li, Yang; Wei, Zhi-Gang; Liu, Gui-Feng

2010-01-01

In aerobic organisms, protection against oxidative damage involves the combined action of highly specialized antioxidant enzymes, such as copper-zinc superoxide dismutase. In this work, a cDNA clone which encodes a copper-zinc superoxide dismutase gene, named PS-CuZnSOD, has been identified from P. sibiricum Laxm. by the rapid amplification of cDNA ends method (RACE). Analysis of the nucleotide sequence reveals that the PS-CuZnSOD gene cDNA clone consists of 669 bp, containing 87 bp in the 5' untranslated region; 459 bp in the open reading frame (ORF) encoding 152 amino acids; and 123 bp in 3' untranslated region. The gene accession nucleotide sequence number in GenBank is GQ472846. Sequence analysis indicates that the protein, like most plant superoxide dismutases (SOD), includes two conserved ecCuZnSOD signatures that are from the amino acids 43 to 51, and from the amino acids 137 to 148, and it has a signal peptide extension in the front of the N-terminus (1-16 aa). Expression analysis by real-time quantitative PCR reveals that the PS-CuZnSOD gene is expressed in leaves, stems and underground stems. PS-CuZnSOD gene expression can be induced by 3% NaHCO(3). The different mRNA levels' expression of PS-CuZnSOD show the gene's different expression modes in leaves, stems and underground stems under the salinity-alkalinity stress.

Cu,Zn superoxide dismutase structure from a microbial pathogen establishes a class with a conserved dimer interface.

PubMed

Forest, K T; Langford, P R; Kroll, J S; Getzoff, E D

2000-02-11

Macrophages and neutrophils protect animals from microbial infection in part by issuing a burst of toxic superoxide radicals when challenged. To counteract this onslaught, many Gram-negative bacterial pathogens possess periplasmic Cu,Zn superoxide dismutases (SODs), which act on superoxide to yield molecular oxygen and hydrogen peroxide. We have solved the X-ray crystal structure of the Cu,Zn SOD from Actinobacillus pleuropneumoniae, a major porcine pathogen, by molecular replacement at 1.9 A resolution. The structure reveals that the dimeric bacterial enzymes form a structurally homologous class defined by a water-mediated dimer interface, and share with all Cu,Zn SODs the Greek-key beta-barrel subunit fold with copper and zinc ions located at the base of a deep loop-enclosed active-site channel. Our structure-based sequence alignment of the bacterial enzymes explains the monomeric nature of at least two of these, and suggests that there may be at least one additional structural class for the bacterial SODs. Two metal-mediated crystal contacts yielded our C222(1) crystals, and the geometry of these sites could be engineered into proteins recalcitrant to crystallization in their native form. This work highlights structural differences between eukaryotic and prokaryotic Cu,Zn SODs, as well as similarities and differences among prokaryotic SODs, and lays the groundwork for development of antimicrobial drugs that specifically target periplasmic Cu,Zn SODs of bacterial pathogens. Copyright 12000 Academic Press.

Activation of CuZn superoxide dismutases from Caenorhabditis elegans does not require the copper chaperone CCS.

PubMed

Jensen, Laran T; Culotta, Valeria Cizewski

2005-12-16

Reactive oxygen species are produced as the direct result of aerobic metabolism and can cause damage to DNA, proteins, and lipids. A principal defense against reactive oxygen species involves the superoxide dismutases (SOD) that act to detoxify superoxide anions. Activation of CuZn-SODs in eukaryotic cells occurs post-translationally and is generally dependent on the copper chaperone for SOD1 (CCS), which inserts the catalytic copper cofactor and catalyzes the oxidation of a conserved disulfide bond that is essential for activity. In contrast to other eukaryotes, the nematode Caenorhabditis elegans does not contain an obvious CCS homologue, and we have found that the C. elegans intracellular CuZn-SODs (wSOD-1 and wSOD-5) are not dependent on CCS for activation when expressed in Saccharomyces cerevisiae. CCS-independent activation of CuZn-SODs is not unique to C. elegans; however, this is the first organism identified that appears to exclusively use this alternative pathway. As was found for mammalian SOD1, wSOD-1 exhibits a requirement for reduced glutathione in CCS-independent activation. Unexpectedly, wSOD-1 was inactive even in the presence of CCS when glutathione was depleted. Our investigation of the cysteine residues that form the disulfide bond in wSOD-1 suggests that the ability of wSODs to readily form this disulfide bond may be the key to obtaining high levels of activation through the CCS-independent pathway. Overall, these studies demonstrate that the CuZn-SODs of C. elegans have uniquely evolved to acquire copper without the copper chaperone and this may reflect the lifestyle of this organism.

Effect of high dietary zinc on plasma ceruloplasmin and erythrocyte superoxide dismutase activities in copper-depleted and repleted rats.

PubMed

Panemangalore, M; Bebe, F N

1996-01-01

The effect of moderately high dietary zinc (Zn) on the activities of plasma (PL) ceruloplasmin (CP), and PL and erythrocyte (RBC) copper (Cu), Zn superoxide dismutase (SOD) was determined in weanling rats fed Cu-deficient (DEF; < 1 mg Cu/kg), marginal (MAR; 2 mg Cu/kg), or control (CON; 5 mg Cu/kg) copper diets containing normal or high Zn (HZn; 60 mg/kg) for 4 wk and supplemented with oral Cu (CuS; 5 mg/L) in drinking water for 0, 1, 3, or 7 d. PL Cu decreased (67% compared to CON; p < or = 0.05) in the DEF and increased to control level after 3 d of CuS; increased in the MAR group after 1 d of CuS. HZn reduced overall PL Cu by 27% in all groups, but did not alter the linear increase in PL Cu between 0 and 3 d of Cu S. PL CP activity altered concomitantly with PL Cu levels: The time course of increase in CP activity after 0-3 d of CuS was not influenced by HZn in the diet and CP declined in the DEF group by 92%. There was no correlation between dietary Cu level and PL CP. PL SOD activity decreased by 46% (p < or = .05) in the DEF group, increased to control activity after 1 d of CuS and declined slightly after 7 d; MAR diet did not alter PL SOD. HZn diet increased PL SOD activity in all groups by 150%, reduced activity in the DEF and MAR groups by 65 and 37% and delayed the recovery of PL SOD after CuS. RBC SOD declined in the DEF and MAR groups by 56 and 33% (p < or = 0.05) and did not respond to CuS; HZn diet did not influence RBC SOD activity. These data indicate that moderately high Zn in the diet reduces PL Cu, but not PL CP activity or the recovery of PL Cu or CP activity after oral CuS of Cu-deficient rats, modifies the response of PL SOD to dietary Cu, but does not influence RBC SOD activity.

Effect of intradermal human recombinant copper-zinc superoxide dismutase on random pattern flaps in rats.

PubMed

Schein, Ophir; Westreich, Melvyn; Shalom, Avshalom

2013-09-01

Studies have focused on enhancing flap viability using superoxide dismutase (SOD), but only a few used SOD from human origin, and most gave the compound systemically. We evaluated the ability of SOD to improve random skin flap survival using human recombinant copper-zinc superoxide dismutase (Hr-CuZnSOD) in variable doses, injected intradermally into the flap. Seventy male Sprague Dawley rats were randomly assigned into 4 groups. Cephalic random pattern flaps were elevated on their backs and intradermal injections of different dosages of Hr-CuZnSOD were given 15 minutes before surgery. Flap survival was evaluated by fluorescein fluorescence. Analysis of variance (ANOVA) and t test statistical analyses were performed. Flap survival in all treated groups was significantly better than in the controls. The beneficial effect of HR-CuZnSOD on flap survival is attained when it is given intradermally into the flap tissue. Theoretically, Hr-CuZnSOD delivered with local anesthetics used in flap elevation may be a valuable clinical tool. Copyright © 2012 Wiley Periodicals, Inc.

High-level expression of a sika deer (Cervus nippon) Cu/Zn superoxide dismutase in Pichia pastoris and its characterization.

PubMed

Li, Ren-Kuan; Fu, Cai-Li; Chen, Ping; Ng, Tzi Bun; Ye, Xiu-Yun

2013-03-01

Production of a sika deer Cu/Zn-SOD was achieved in Pichia pastoris after the reconstituted expression vector pPIC9K was transformed into the strain GS115. By employing Saccharomyces cerevisiae secretion signal peptide (α-factor) under the regulation of the methanol-inducible promoter of the gene of alcohol oxidase 1 (AOX1), sika deer Cu/Zn-SOD with a molecular mass of 16kDa was expressed while recombinant sika deer Cu/Zn-SOD with an activity of 3500U/mL was obtained from a 5L bioreactor. After two successive steps of chromatography on DEAE-650C and Superdex75, recombinant sika deer Cu/Zn-SOD was obtained with 13.8% yield, 14.5-fold purification, and a specific activity of 3447U/mg. Its optimum temperature and optimum pH were 40°C and 7.0, respectively. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

CuZnSOD gene deletion targeted to skeletal muscle leads to loss of contractile force but does not cause muscle atrophy in adult mice

PubMed Central

Zhang, Yiqiang; Davis, Carol; Sakellariou, George K.; Shi, Yun; Kayani, Anna C.; Pulliam, Daniel; Bhattacharya, Arunabh; Richardson, Arlan; Jackson, Malcolm J.; McArdle, Anne; Brooks, Susan V.; Van Remmen, Holly

2013-01-01

We have previously shown that deletion of CuZnSOD in mice (Sod1−/− mice) leads to accelerated loss of muscle mass and contractile force during aging. To dissect the relative roles of skeletal muscle and motor neurons in this process, we used a Cre-Lox targeted approach to establish a skeletal muscle-specific Sod1-knockout (mKO) mouse to determine whether muscle-specific CuZnSOD deletion is sufficient to cause muscle atrophy. Surprisingly, mKO mice maintain muscle masses at or above those of wild-type control mice up to 18 mo of age. In contrast, maximum isometric specific force measured in gastrocnemius muscle is significantly reduced in the mKO mice. We found no detectable increases in global measures of oxidative stress or ROS production, no reduction in mitochondrial ATP production, and no induction of adaptive stress responses in muscle from mKO mice. However, Akt-mTOR signaling is elevated and the number of muscle fibers with centrally located nuclei is increased in skeletal muscle from mKO mice, which suggests elevated regenerative pathways. Our data demonstrate that lack of CuZnSOD restricted to skeletal muscle does not lead to muscle atrophy but does cause muscle weakness in adult mice and suggest loss of CuZnSOD may potentiate muscle regenerative pathways.—Zhang, Y., Davis, C., Sakellariou, G.K., Shi, Y., Kayani, A.C., Pulliam, D., Bhattacharya, A., Richardson, A., Jackson, M.J., McArdle, A., Brooks, S.V., Van Remmen, H. CuZnSOD gene deletion targeted to skeletal muscle leads to loss of contractile force but does not cause muscle atrophy in adult mice. PMID:23729587

Isolation and characterization of Cu/Zn-superoxide dismutase in Fasciola gigantica.

PubMed

Lalrinkima, H; Raina, O K; Chandra, Dinesh; Jacob, Siju Susan; Bauri, R K; Chandra, Subhash; Yadav, H S; Singh, M N; Rialch, A; Varghese, A; Banerjee, P S; Kaur, Navneet; Sharma, Arvind

2015-01-01

A full-length complementary DNA (cDNA) encoding Cu/Zn-superoxide dismutase was isolated from Fasciola gigantica that on nucleotide sequencing showed a close homology (98.9%) with Cu/Zn-superoxide dismutase (SOD) of the temperate liver fluke, F. hepatica. Expression of the gene was found in all the three developmental stages of the parasite viz. adult, newly excysted juvenile and metacercaria at transcriptional level by reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. F. gigantica Cu/Zn-SOD cDNA was cloned and expressed in Escherichia coli. Enzyme activity of the recombinant protein was determined by nitroblue tetrazolium (NBT)-polyacrylamide gel electrophoresis (PAGE) and this activity was inactivated by hydrogen peroxide but not by sodium azide, indicating that the recombinant protein is Cu/Zn-SOD. The enzyme activity was relatively stable at a broad pH range of pH 4.0-10.0. Native Cu/Zn-superoxide dismutase protein was detected in the somatic extract and excretory-secretory products of the adult F. gigantica by Western blotting. NBT-PAGE showed a single Cu/Zn-SOD present in the somatic extract while three SODs are released ex vivo by the adult parasite. The recombinant superoxide dismutase did not react with the serum from buffaloes infected with F. gigantica. The role of this enzyme in defense by the parasite against the host reactive oxygen species is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of copper, manganese and zinc on plant growth and elemental accumulation in the manganese-hyperaccumulator Phytolacca americana.

PubMed

Zhao, Huijun; Wu, Liangqi; Chai, Tuanyao; Zhang, Yuxiu; Tan, Jinjuan; Ma, Shengwen

2012-09-01

Synchrotron radiation X-ray fluorescence (SRXRF) and inductively coupled plasma mass spectrometry were used to estimate major, minor and trace elements in Cu-, Zn- and Mn-treated Phytolacca americana. The effects of the addition of Cu, Zn and Mn on morphological parameters, such as root length, shoot height, and fresh and dry weights of shoots and roots, were also examined. In addition, the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidases (GPX) and catalase (CAT) and the expression of Fe-SOD, Cu/Zn-SOD, metallothionein-2 and glutathione S-transferase (GST) exposed to the highest amounts of Cu, Zn or Mn were detected. Our results confirmed the following: (1) Zn supplementation leads to chlorosis, disturbed elemental homeostasis and decreased concentrations of micro- and macroelements such as Fe, Mg, Mn, Ca and K. Cu competed with Fe, Mn and Zn uptake in plants supplemented with 25 μM Cu. However, no antagonistic interactions took place between Cu, Zn, Mn and Fe uptake in plants supplemented with 100 μM Cu. Mn supplementation at various concentrations had no negative effects on elemental deficits. Mn was co-located with high concentrations of Fe and Zn in mature leaves and the concentrations of macro elements were unchanged. (2) P. americana supplemented with increased concentrations of Zn and Cu exhibited lower biomass production and reduced plant growth. (3) When plants were supplemented with the highest Zn and Cu concentrations, symptoms of toxicity corresponded to decreased SOD or CAT activities and increased APX and GPX activities. However, Mn tolerance corresponded to increased SOD and CAT activities and decreased POD and APX activities. Our study revealed that heavy metals partially exert toxicity by disturbing the nutrient balance and modifying enzyme activities that induce damage in plants. However, P. americana has evolved hyper accumulating mechanisms to maintain elemental balance and redox homeostasis under excess Mn. Copyright © 2012 Elsevier GmbH. All rights reserved.

An elevated level of copper zinc superoxide dismutase fails to prevent oxygen induced retinopathy in mice.

PubMed

Klaeger, C; de Sa, L; Klaeger, A J; Carlson, E J; Good, W V; Epstein, C J

1996-05-01

To determine whether a higher level of copper zinc superoxide dismutase (CuZnSOD) can reduce the severity of oxygen induced retinopathy (OIR) in a mouse model. CuZnSOD transgenic mice with a threefold increase in CuZnSOD activity and control non-transgenic mice were exposed to 90% oxygen for 12 hours a day during the first 5 days of life. After oxygen treatment, all mice were reared in room air for 10 days. Another group of transgenic and non-transgenic mice were kept in room air for 15 days and served as control groups for the oxygen effect. At day 15, all mice were killed and perfused with India ink. The retinas were flat mounted on slides and examined with a light microscope. There was a statistically significant increase in the incidence of OIR in mice exposed to high levels of oxygen, whether or not they were transgenic. However, there was no statistically significant difference in the severity of OIR between oxygen treated transgenic and non-transgenic mice. A threefold higher CuZnSOD activity does not protect against OIR in mice. This is an unexpected finding, since oxygen radicals are considered a major factor causing OIR, and increased CuZnSOD activity has reduced oxygen radical induced damage in several neuronal and non-neuronal systems. The possibility of a damaging role for other radicals not affected by CuZnSOD cannot be excluded.

Localization of superoxide dismutases and hydrogen peroxide in legume root nodules.

PubMed

Rubio, Maria C; James, Euan K; Clemente, Maria R; Bucciarelli, Bruna; Fedorova, Maria; Vance, Carroll P; Becana, Manuel

2004-12-01

Superoxide dismutases (SODs) catalyze the dismutation of superoxide radicals to O2 and H2O2 and thus represent a primary line of antioxidant defense in all aerobic organisms. H2O2 is a signal molecule involved in the plant's response to pathogen attack and other stress conditions as well as in nodulation. In this work, we have tested the hypothesis that SODs are a source of H2O2 in indeterminate alfalfa (Medicago sativa) and pea (Pisum sativum) nodules. The transcripts and proteins of the major SODs of nodules were localized by in situ RNA hybridization and immunogold electron microscopy, respectively, whereas H2O2 was localized cytochemically by electron microscopy of cerium-perfused nodule tissue. The transcript and protein of cytosolic CuZnSOD are most abundant in the meristem (I) and invasion (II) zones, interzone II-III, and distal part of the N2-fixing zone (III), and those of MnSOD in zone III, especially in the infected cells. At the subcellular level, CuZnSOD was found in the infection threads, cytosol adjacent to cell walls, and apoplast, whereas MnSOD was in the bacteroids, bacteria within infection threads, and mitochondria. The distinct expression pattern of CuZnSOD and MnSOD suggests specific roles of the enzymes in nodules. Large amounts of H2O2 were found at the same three nodule sites as CuZnSOD but not in association with MnSOD. This colocalization led us to postulate that cytosolic CuZnSOD is a source of H2O2 in nodules. Furthermore, the absence or large reduction of H2O2 in nodule tissue preincubated with enzyme inhibitors (cyanide, azide, diphenyleneiodonium, diethyldithiocarbamate) provides strong support to the hypothesis that at least some of the H2O2 originates by the sequential operation of an NADPH oxidase-like enzyme and CuZnSOD. Results also show that there is abundant H2O2 associated with degrading bacteroids in the senescent zone (IV), which reflects the oxidative stress ensued during nodule senescence.

Characteristics of the Copper,Zinc Superoxide Dismutase of a Hadal Sea Cucumber (Paelopatides sp.) from the Mariana Trench.

PubMed

Li, Yanan; Kong, Xue; Chen, Jiawei; Liu, Helu; Zhang, Haibin

2018-05-18

Superoxide dismutases (SODs) are among the most important antioxidant enzymes and show great potential in preventing adverse effects during therapeutic trials. In the present study, cloning, expression, and characterization of a novel Cu,Zn superoxide dismutase (Ps-Cu,Zn-SOD) from a hadal sea cucumber ( Paelopatides sp.) were reported. Phylogenetic analysis showed that Ps-Cu,Zn-SOD belonged to a class of intracellular SOD. Its K m and V max were 0.0258 ± 0.0048 mM and 925.1816 ± 28.0430 units/mg, respectively. The low K m value of this enzyme represents a high substrate affinity and can adapt to the low metabolic rate of deep sea organisms. The enzyme functioned from 0 °C to 80 °C with an optimal temperature of 40 °C. Moreover, the enzyme activity was maintained up to 87.12% at 5 °C. The enzyme was active at pH 4 to 12 with an optimal pH of 8.5. Furthermore, Ps-Cu,Zn-SOD tolerated high concentration of urea and GuHCl, resisted hydrolysis by proteases, and maintained stability at high pressure. All these features demonstrated that the deep sea Ps-Cu,Zn-SOD is a potential candidate for application to the biopharmaceutical field.

Coal-burning endemic fluorosis is associated with reduced activity in antioxidative enzymes and Cu/Zn-SOD gene expression.

PubMed

Wang, Qi; Cui, Kang-ping; Xu, Yuan-yuan; Gao, Yan-ling; Zhao, Jing; Li, Da-sheng; Li, Xiao-lei; Huang, Hou-jin

2014-02-01

To study the effect of fluorine on the oxidative stress in coal-burning fluorosis, we investigated the environmental characteristics of coal-burning endemic fluorosis combined with fluorine content surveillance in air, water, food, briquette, and clay binder samples from Bijie region, Guizhou Province, southwest of China. The activities of antioxidant enzymes including copper/zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and level of lipid peroxidation such as malondialdehyde (MDA) were measured in serum samples obtained from subjects residing in the Bijie region. Expression of the Cu/Zn-SOD gene was assessed by quantitative reverse transcriptase PCR (qRT-PCR). Our results showed that people suffering from endemic fluorosis (the high and low exposure groups) had much higher MDA level. Their antioxidant enzyme activities and Cu/Zn-SOD gene expression levels were lower when compared to healthy people (the control group). Fluorosis can decrease the activities of antioxidant enzymes, which was associated with exposure level of fluorine. Down-regulation of Cu/Zn-SOD expression may play an important role in the aggravation of oxidative stress in endemic fluorosis.

AMELIORATION OF ETHANOL-INDUCED DYSMORPHOGENESIS BY ADENOVIRAL-MEDIATED CU,ZN-SOD AND MN-SOD EXPRESSION IN NEURULATION STAGED MOUSE EMBRYOS IN VITRO

EPA Science Inventory

AMELIORATION OF ETHANOL-INDUCED DYSMORPHOGENESIS BY ADENOVIRAL-MEDIATED Cu,Zn-SOD AND Mn-SOD EXPRESSION IN NEURULATION STAGED MOUSE EMBRYOS IN VITRO. JB Smith1, PC Hartig3, MR Blanton3, KK Sulik1,2, and ES Hunter3. 1Department of Cell and Developmental Biology and 2Bowles Cente...

Exposure of Mn and FeSODs, but not Cu/ZnSOD, to NO leads to nitrosonium and nitroxyl ions generation which cause enzyme modification and inactivation: an in vitro study.

PubMed

Niketíc, V; Stojanović, S; Nikolić, A; Spasić, M; Michelson, A M

1999-11-01

The effect of NO treatment in vitro on structural and functional alterations of Cu/Zn, Mn, and Fe type of SODs was studied. Significant difference in response to NO of Cu/ZnSOD compared to the Mn and Fe types was demonstrated. Cu/ZnSOD was shown to be stable with respect to NO: even on prolonged exposure, NO produced negligible effect on its structure and activity. In contrast, both Mn and Fe types were found to be NO-sensitive: exposure to NO led to their fast and extensive inactivation, which was accompanied by extensive structural alterations, including (in some of the samples tested) the cleavage of enzyme polypeptide chains, presumably at His residues of the enzyme metal binding sites. The generation of nitrosonium (NO+) and nitroxyl (NO-) ions in NO treated Mn and FeSODs, which produce enzyme modifications and inactivation, was demonstrated. The physiological and biomedical significance of described findings is briefly discussed.

Copper, Zinc Superoxide Dismutase is Primarily a Cytosolic Protein in Human Cells

NASA Astrophysics Data System (ADS)

Crapo, James D.; Oury, Tim; Rabouille, Catherine; Slot, Jan W.; Chang, Ling-Yi

1992-11-01

The intracellular localization of human copper, zinc superoxide dismutase (Cu,Zn-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) was evaluated by using EM immunocytochemistry and both isolated human cell lines and human tissues. Eight monoclonal antibodies raised against either native or recombinant human Cu,Zn-SOD and two polyclonal antibodies raised against either native or recombinant human Cu,Zn-SOD were used. Fixation with 2% paraformaldehyde/0.2% glutaraldehyde was found necessary to preserve normal distribution of the protein. Monoclonal antibodies were less effective than polyclonal antibodies in recognizing the antigen after adequate fixation of tissue. Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus, consistent with it being a soluble cytosolic protein. Mitochondria and secretory compartments did not label for this protein. In human cells, peroxisomes showed a labeling density slightly less than that of cytoplasm.

Unique molecular properties of superoxide dismutase from teleost fish skin.

PubMed

Nakano, T; Sato, M; Takeuchi, M

1995-02-27

A unique Cu,Zn-SOD was found and isolated from plaice Paralichthys olivaceus skin. Surprisingly, the properties of purified fish skin SOD were very different from those of SOD from other sources reported so far. The purified SOD was composed of four same subunits of 16 kDa and the molecular weight of the native SOD was found to be around 65 kDa. The dominant amino acids of the SOD were Ser, Thr, Pro and Glu. Above 70 degrees C, thermostability of the SOD was much lower than that of bovine erythrocyte Cu,Zn-SOD.

Erythrocyte CuZn superoxide dismutase activity is decreased in iron-deficiency anemia.

PubMed

Olivares, M; Araya, M; Pizarro, F; Letelier, A

2006-09-01

Iron and copper are essential microminerals that are intimately related. The present study was performed to determine the effect of iron-deficiency anemia (IDA) and treatment with iron on laboratory indicators of copper status. Hemoglobin, mean corpuscular volume erythrocyte Zn protoporphyrin, serum ferritin, serum copper, serum ceruloplasmin, and erythrocyte CuZn-superoxide dismutase (SOD) activity were studied in 12 adult women with IDA before and after iron treatment for 60-90 d (100 mg/d Fe, as ferric polymaltose) and in 27 women with normal iron status. Prior to treatment with iron, serum copper and ceruloplasmin were not different between the groups and treatment with iron did not affect these measures. IDA women, before and after treatment with iron, presented a 2.9- and 2-fold decrease in erythrocyte CuZn-SOD activity compared to women with normal iron status (p < 0.001). Treatment with iron increased erythrocyte CuZn-SOD activity of the IDA group; however, this change was not statistically significant. In conclusion, CuZn-SOD activity is decreased in IDA. Measurement of this enzyme activity is not useful for evaluating copper nutrition in iron-deficient subjects.

Intestinal cell targeting of a stable recombinant Cu-Zn SOD from Cucumis melo fused to a gliadin peptide.

PubMed

Intes, Laurent; Bahut, Muriel; Nicole, Pascal; Couvineau, Alain; Guette, Catherine; Calenda, Alphonse

2012-05-31

The mRNA encoding full length chloroplastic Cu-Zn SOD (superoxide dismutase) of Cucumis melo (Cantaloupe melon) was cloned. This sequence was then used to generate a mature recombinant SOD by deleting the first 64 codons expected to encode a chloroplastic peptide signal. A second hybrid SOD was created by inserting ten codons to encode a gliadin peptide at the N-terminal end of the mature SOD. Taking account of codon bias, both recombinant proteins were successfully expressed and produced in Escherichia coli. Both recombinant SODs display an enzymatic activity of ~5000U mg(-1) and were shown to be stable for at least 4h at 37°C in biological fluids mimicking the conditions of intestinal transit. These recombinant proteins were capable in vitro, albeit at different levels, of reducing ROS-induced-apoptosis of human epithelial cells. They also stimulated production and release in a time-dependent manner of an autologous SOD activity from cells located into jejunum biopsies. Nevertheless, the fused gliadin peptide enable the recombinant Cu-Zn SOD to maintain a sufficiently sustained interaction with the intestinal cells membrane in vivo rather than being eliminated with the flow. According to these observations, the new hybrid Cu-Zn SOD should show promise in applications for managing inflammatory bowel diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

Copper exposure induces oxidative injury, disturbs the antioxidant system and changes the Nrf2/ARE (CuZnSOD) signaling in the fish brain: protective effects of myo-inositol.

PubMed

Jiang, Wei-Dan; Liu, Yang; Hu, Kai; Jiang, Jun; Li, Shu-Hong; Feng, Lin; Zhou, Xiao-Qiu

2014-10-01

The brain is the center of the nervous system in all vertebrates, and homeostasis of the brain is crucial for fish survival. Copper (Cu) is essential for normal cellular processes in most eukaryotic organisms but is toxic in excess. Although Cu is indicated as a potent neurotoxicant, information regarding its threat to fish brain and underlying mechanisms is still scarce. In accordance, the objective of this study was to assess the effects and the potential mechanism of Cu toxicity by evaluating brain oxidative status, the enzymatic and mRNA levels of antioxidant genes, as well as the Nrf2/ARE signaling in the brain of fish after Cu exposure. The protective effects of myo-inositol (MI) against subsequent Cu exposure were also investigated. The results indicate that induction of oxidative stress by Cu is shown by increases in brain ROS production, lipid peroxidation and protein oxidation, which are accompanied by depletions of antioxidants, including total superoxide dismutase (T-SOD), CuZnSOD, glutathione-S-transferase (GST) and glutathione reductase (GR) activities and glutathione (GSH) content. Cu exposure increased the catalase (CAT) and glutathione peroxidase (GPx) activities. Further molecular results showed that Cu exposure up-regulated CuZnSOD, GPx1a and GR mRNA levels, suggesting an adaptive mechanism against stress. Moreover, Cu exposure increased fish brain Nrf2 nuclear accumulation and increased its ability of binding to ARE (CuZnSOD), which supported the increased CuZnSOD mRNA levels. In addition, Cu exposure caused increases of the expression of the Nrf2, Maf G1 (rather than Maf G2 gene) and PKCd genes, suggesting that de novo synthesis of those factors is required for the protracted induction of such antioxidant genes. However, the modulation of Keap1a (rather than Keap1b) of fish brain under Cu exposure might be used to turn off of the signaling cascade and avoid harmful effects. Interestingly, pre-treatment of fish with MI prevented the fish brain from Cu-induced oxidative damages mainly by increasing the GSH content and CuZnSOD and GST activities. Summarily, this study indicates that although Cu stimulates adaptive increases in the expression of some antioxidant enzyme genes through Nrf2/ARE signaling, it also induces oxidation and the depletion of most of antioxidant enzyme activities and GSH content due to the increase of ROS production, and MI protects the fish brain against Cu toxicity. Copyright © 2014 Elsevier B.V. All rights reserved.

Activation of Cu,Zn-superoxide dismutase in the absence of oxygen and the copper chaperone CCS.

PubMed

Leitch, Jeffry M; Jensen, Laran T; Bouldin, Samantha D; Outten, Caryn E; Hart, P John; Culotta, Valeria C

2009-08-14

Eukaryotic Cu,Zn-superoxide dismutases (SOD1s) are generally thought to acquire the essential copper cofactor and intramolecular disulfide bond through the action of the CCS copper chaperone. However, several metazoan SOD1s have been shown to acquire activity in vivo in the absence of CCS, and the Cu,Zn-SOD from Caenorhabditis elegans has evolved complete independence from CCS. To investigate SOD1 activation in the absence of CCS, we compared and contrasted the CCS-independent activation of C. elegans and human SOD1 to the strict CCS-dependent activation of Saccharomyces cerevisiae SOD1. Using a yeast expression system, both pathways were seen to acquire copper derived from cell surface transporters and compete for the same intracellular pool of copper. Like CCS, CCS-independent activation occurs rapidly with a preexisting pool of apo-SOD1 without the need for new protein synthesis. The two pathways, however, strongly diverge when assayed for the SOD1 disulfide. SOD1 molecules that are activated without CCS exhibit disulfide oxidation in vivo without oxygen and under copper-depleted conditions. The strict requirement for copper, oxygen, and CCS in disulfide bond oxidation appears exclusive to yeast SOD1, and we find that a unique proline at position 144 in yeast SOD1 is responsible for this disulfide effect. CCS-dependent and -independent pathways also exhibit differential requirements for molecular oxygen. CCS activation of SOD1 requires oxygen, whereas the CCS-independent pathway is able to activate SOD1s even under anaerobic conditions. In this manner, Cu,Zn-SOD from metazoans may retain activity over a wide range of physiological oxygen tensions.

Copper/zinc and copper/selenium ratios, and oxidative stress as biochemical markers in recurrent aphthous stomatitis.

PubMed

Ozturk, Perihan; Belge Kurutas, Ergul; Ataseven, Arzu

2013-10-01

Recurrent aphthous stomatitis (RAS) is a common oral mucosal disorder characterized by recurrent, painful oral aphthae, and oxidative stress presumably contributes to its pathogenesis. The aim of this study is to scrutinize the relationship between oxidative stress and serum trace elements (copper, Cu; zinc, Zn; selenium, Se), and to evaluate the ratios of Cu/Zn and Cu/Se in this disorder. Patients with RAS (n = 33) and age- and sex-matched healthy control subjects (n = 30) were enrolled in this study. Malondialdehyde (MDA) concentrations in plasma and the activities of superoxide dismutase (SOD1; CuZnSOD), glutathione peroxidase (GPx) and catalase (CAT) in erythrocyte were determined as spectrophotometric. Also, the levels of Se, Zn and Cu in serum were determined on flame and furnace atomic absorption spectrophotometer using Zeeman background correction. Oxidative stress was confirmed by the significant elevation in plasma MDA, and by the significant decrease in CAT, SOD1, and GPx (p < 0.05). When compared to controls, Zn and Se levels were significantly lower in patients, whereas Cu levels was higher in RAS patients than those in controls (p < 0.05). In addition, the correlation results of this study were firstly shown that there were significant and positive correlations between Se-CAT, Se-GPx, and Cu-MDA parameters, but negative correlations between Se-Cu, Se-MDA, Cu-CAT, Cu-SOD1 and Cu-GPx parameters in RAS patients. Furthermore, the ratios of Cu/Zn and Cu/Se were significantly higher in the patients than the control subjects (p < 0.05). Our results indicated that lipid peroxidation associated with the imbalance of the trace elements seems to play a crucial role in the pathogenesis of RAS. Furthermore, the serum Cu/Zn and Cu/Se ratios may be used as biochemical markers in these patients. Crown Copyright © 2013. Published by Elsevier GmbH. All rights reserved.

Novel inhibitors to Taenia solium Cu/Zn superoxide dismutase identified by virtual screening

NASA Astrophysics Data System (ADS)

García-Gutiérrez, P.; Landa-Piedra, A.; Rodríguez-Romero, A.; Parra-Unda, R.; Rojo-Domínguez, A.

2011-12-01

We describe in this work a successful virtual screening and experimental testing aimed to the identification of novel inhibitors of superoxide dismutase of the worm Taenia solium ( TsCu/Zn-SOD), a human parasite. Conformers from LeadQuest® database of drug-like compounds were selected and then docked on the surface of TsCu/Zn-SOD. Results were screened looking for ligand contacts with receptor side-chains not conserved in the human homologue, with a subsequent development of a score optimization by a set of energy minimization steps, aimed to identify lead compounds for in vitro experiments. Six out of fifty experimentally tested compounds showed μM inhibitory activity toward TsCu/Zn-SOD. Two of them showed species selectivity since did not inhibit the homologous human enzyme when assayed in vitro.

Mining the enzymes involved in the detoxification of reactive oxygen species (ROS) in sugarcane.

PubMed

Kurama, Eiko E; Fenille, Roseli C; Rosa, Vicente E; Rosa, Daniel D; Ulian, Eugenio C

2002-07-01

Summary Adopting the sequencing of expressed sequence tags (ESTs) of a sugarcane database derived from libraries induced and not induced by pathogens, we identified EST clusters homologous to genes corresponding to enzymes involved in the detoxification of reactive oxygen species. The predicted amino acids of these enzymes are superoxide dismutases (SODs), glutathione-S-transferase (GST), glutathione peroxidase (GPX), and catalases. Three MnSOD mitochondrial precursors and 10 CuZnSOD were identified in sugarcane: the MnSOD mitochondrial precursor is 96% similar to the maize MnSOD mitochondrial precursor and, of the 10 CuZnSOD identified, seven were 98% identical to maize cytosolic CuZnSOD4 and one was 67% identical to putative peroxisomal CuZnSOD from Arabidopsis. Three homologues to class Phi GST were 87-88% identical to GST III from maize. Five GPX homologues were identified: three were homologous to cytosolic GPX from barley, one was 88% identical to phospholipid hydroperoxide glutathione peroxidase (PHGPX) from rice, and the last was 71% identical to GPX from A. thaliana. Three enzymes similar to maize catalase were identified in sugarcane: two were similar to catalase isozyme 3 and catalase chain 3 from maize, which are mitochondrial, and one was similar to catalase isozyme 1 from maize, whose location is peroxisomal subcellular. All enzymes were induced in all sugarcane libraries (flower, seed, root, callus, leaves) and also in the pathogen-induced libraries, except for CuZnSOD whose cDNA was detected in none of the libraries induced by pathogens (Acetobacter diazotroficans and Herbaspirillum rubrisubalbicans). The expression of the enzymes SOD, GST, GPX, and catalases involved in the detoxification was examined using reverse transcriptase-polymerase chain reaction in cDNA from leaves of sugarcane under biotic stress conditions, inoculated with Puccinia melanocephala, the causal agent of sugarcane rust disease.

Endotoxin treatment protects rats against ozone-induced lung edema: with evidence for the role of manganese superoxide dismutase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahman, I.; Massaro, D.

Ozone is a strong oxidizing agent that can cause lung damage and edema. There is evidence that it does so by causing peroxidation of membrane lipids. However, the elevation in lung activity of copper, zinc superoxide dismutase (Cu, ZnSOD), and manganese superoxide dismutase (MnSOD) during exposure to ozone suggests that increased production of superoxide could contribute to lung edema caused by ozone. This latter observation, and preliminary evidence that treatment of rats with endotoxin elevates lung activity of MnSOD without elevation of the activity of Cu, ZnSOD, catalase (CAT), or glutathione peroxidase (GP), led to the present study. We treatedmore » rats with endotoxin, exposed them to different concentrations of ozone, measured lung wet weight to dry weight ratio, thiobarbituric acid-reactive material (TBAR), and assayed lung tissue for Cu, ZnSOD, MnSOD, CAT, and GP activity. Our major findings are, (1) a strongly edemogenic concentration of ozone-lowered MnSOD activity; (2) endotoxin treatment of air-breathing rats did not decrease lipid peroxidation as indicated by the lung concentration of TBAR; (3) induction of increased MnSOD activity in lung by treatment with endotoxin was associated with virtually complete protection against an otherwise edemogenic concentration of ozone, with less lipid peroxidation, and with less loss of weight; and (4) this protection occurred without elevated Cu, ZnSOD, CAT, or GP activity.« less

Mechanisms for activating Cu- and Zn-containing superoxide dismutase in the absence of the CCS Cu chaperone.

PubMed

Carroll, Mark C; Girouard, Jody B; Ulloa, Janella L; Subramaniam, Jamuna R; Wong, Phillip C; Valentine, Joan Selverstone; Culotta, Valeria Cizewski

2004-04-20

The Cu- and Zn-containing superoxide dismutase 1 (SOD1) largely obtains Cu in vivo by means of the action of the Cu chaperone CCS. Yet, in the case of mammalian SOD1, a secondary pathway of activation is apparent. Specifically, when human SOD1 is expressed in either yeast or mammalian cells that are null for CCS, the SOD1 enzyme retains a certain degree of activity. This CCS-independent activity is evident with both wild-type and mutant variants of SOD1 that have been associated with familial amyotrophic lateral sclerosis. We demonstrate here that the CCS-independent activation of mammalian SOD1 involves glutathione, particularly the reduced form, or GSH. A role for glutathione in CCS-independent activation was seen with human SOD1 molecules that were expressed in either yeast cells or immortalized fibroblasts. Compared with mammalian SOD1, the Saccharomyces cerevisiae enzyme cannot obtain Cu without CCS in vivo, and this total dependence on CCS involves the presence of dual prolines near the C terminus of the SOD1 polypeptide. Indeed, the insertion of such prolines into human SOD1 rendered this molecule refractory to CCS-independent activation. The possible implications of multiple pathways for SOD1 activation are discussed in the context of SOD1 evolutionary biology and familial amyotrophic lateral sclerosis.

Gene expression and activity of antioxidant enzymes in rice plants, cv. BRS AG, under saline stress.

PubMed

Rossatto, Tatiana; do Amaral, Marcelo Nogueira; Benitez, Letícia Carvalho; Vighi, Isabel Lopes; Braga, Eugenia Jacira Bolacel; de Magalhães Júnior, Ariano Martins; Maia, Mara Andrade Colares; da Silva Pinto, Luciano

2017-10-01

The rice cultivar ( Oryza sativa L.) BRS AG, developed by Embrapa Clima Temperado, is the first cultivar designed for purposes other than human consumption. It may be used in ethanol production and animal feed. Different abiotic stresses negatively affect plant growth. Soil salinity is responsible for a serious reduction in productivity. Therefore, the objective of this study was to evaluate the gene expression and the activity of antioxidant enzymes (SOD, CAT, APX and GR) and identify their functions in controlling ROS levels in rice plants, cultivar BRS AG, after a saline stress period. The plants were grown in vitro with two NaCl concentrations (0 and 136 mM), collected at 10, 15 and 20 days of cultivation. The results indicated that the activity of the enzymes evaluated promotes protection against oxidative stress. Although, there was an increase of reactive oxygen species, there was no increase in MDA levels. Regarding genes encoding isoforms of antioxidant enzymes, it was observed that OsSOD3 - CU/Zn , OsSOD2 - Cu/Zn , OsSOD - Cu/Zn , OsSOD4 - Cu/Zn , OsSODCc1 - Cu/Zn , OsSOD - Fe , OsAPX1 , OsCATB and OsGR2 were the most responsive. The increase in the transcription of all genes among evaluated isoforms, except for OsAPX6 , which remained stable, contributed to the increase or the maintenance of enzyme activity. Thus, it is possible to infer that the cv. BRS AG has defense mechanisms against salt stress.

Purification and properties of Cu-Zn superoxide dismutase extracted from Brucella abortus strain 19

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tabatabai, L.B.

Recent work showed that a recombinant 20 kDa protein from Brucella abortus expressed in E. coli is a Cu-Zn superoxide dismutase (SOD). Western blot and ELISA results indicated that cattle with brucellosis have antibody to SOD. Here the authors report the purification and properties of the native B. abortus Cu-Zn SOD. SOD was extracted from methanol-killed Brucella abortus strain 19 with 0.1 M sodium citrate-1.0 M sodium chloride solution. The extract was dialyzed and protein precipitated by ammonium sulfate at 70-100% saturation was collected. The SOD was purified by HPLC anion exchange chromatography. SOD activity was assayed with a coupledmore » enzyme assay using xanthine oxidase-cytochrome C reduction assay. The authors determined that the Brucella SOD is present in two molecular forms both inhibitable with KCN with Ki's of 0.32 mM and 4.98 mM, respectively. No other form of SOD was identified in the extract. Polyclonal antibody to SOD and polyclonal antibody to SOD synthetic peptide residues 134-143 inhibited SOD activity by 50% and 13%, respectively. Both SOD and the synthetic peptide inhibited binding of anti-SOD antibody to SOD by 60% and 20%, respectively. Based on these results the SOD and its amphipathic peptide will be considered as candidates for the design of synthetic multiple peptide vaccines and diagnostic reagents for bovine brucellosis.« less

Metallochaperone for Cu,Zn-superoxide dismutase (CCS) protein but not mRNA is higher in organs from copper-deficient mice and rats.

PubMed

Prohaska, Joseph R; Broderius, Margaret; Brokate, Bruce

2003-09-15

Cu,Zn-superoxide dismutase (SOD1) is an abundant metalloenzyme important in scavenging superoxide ions. Cu-deficient rats and mice have lower SOD1 activity and protein, possibly because apo-SOD1 is degraded faster than holo-SOD1. SOD1 interacts with and requires its metallochaperone CCS for donating copper. We produced dietary Cu deficiency in rodents to determine if the reduction in SOD1 was related to the level of its specific metallochaperone CCS. CCS levels determined by immunoblot were 2- to 3-fold higher in liver, heart, kidney, and brain from male Cu-deficient rats and mice under a variety of conditions. CCS was also higher in livers of Cu-deficient dams. Interestingly, CCS levels in brain of Cu-deficient mice were also higher even though SOD1 activity and protein were not altered, suggesting that the rise in CCS is correlated with altered Cu status rather than a direct result of lower SOD1. A DNA probe specific for rat CCS detected a single transcript by Northern blot hybridization with liver RNA. CCS mRNA levels in mouse and rat liver were not altered by dietary treatment. These results suggest a posttranscriptional mechanism for higher CCS protein when Cu is limiting in the cell, perhaps due to slower protein turnover. Elevation in CCS level is one of the most dramatic alterations in Cu binding proteins accompanying Cu deficiency and may be useful to assess Cu status.

Inflammation protects copper deficient rats from carbon tetrachloride toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, F.L.; Joseph, E.; DiSilvestro, R.A.

1991-03-11

Copper deficient rats show low resistance to CCl{sub 4}, possibly due to low liver Cu-Zn superoxide dismutase (SOD) activities. If Cu-Zn SOD is involved, deficiency effects should be aggravated by inflammation which further lowers Cu-Zn SOD activities in deficient rats. On the contrary, inflammation from 0.1 ml turpentine (im, lef) protected these rats from CCl{sub 4} damage assessed by serum activities of 2 liver enzymes. CCl{sub 4} was given ip at 200 {mu}l/kg, 48 h after turpentine, 24 h before sacrifice. Rats were fed low copper for 40 days before CCl{sub 4} challenge. Inflammation also protected rats fed adequate coppermore » from injury, though injury in noninflamed rats was less than with noninflamed deficients. Protection could result from the large increase observed in liver metallothionein, an induction not restricted by copper deficiency. Alternatively, inflammation may block P-450 activation of CCl{sub 4}. Both explanations are currently under investigation, as is the role, if any, of Cu-Zn SOD in resisting CCl{sub 4} injury.« less

Exploration of Molecular Factors Impairing Superoxide Dismutase Isoforms Activity in Human Senile Cataractous Lenses

PubMed Central

Rajkumar, Sankaranarayanan; Vasavada, Abhay R.; Praveen, Mamidipudi R.; Ananthan, Rajendran; Reddy, Geereddy B.; Tripathi, Harsha; Ganatra, Darshini A.; Arora, Anshul I.; Patel, Alpesh R.

2013-01-01

Purpose. To explore different molecular factors impairing the activities of superoxide dismutase (SOD) isoforms in senile cataractous lenses. Methods. Enzyme activity of SOD isoforms, levels of their corresponding cofactors copper (Cu), manganese (Mn), zinc (Zn), and expression of mRNA transcripts and proteins were determined in the lenses of human subjects with and without cataract. DNA from lens epithelium (LE) and peripheral blood was isolated. Polymerase chain reaction–single strand conformation polymorphism (PCR-SSCP) followed by sequencing was carried out to screen somatic mutations. The impact of intronic insertion/deletion (INDEL) variations on the splicing process and on the resultant transcript was evaluated. Genotyping of IVS4+42delG polymorphism of SOD1 gene was done by PCR–restriction fragment length polymorphism (RFLP). Results. A significant decrease in Cu/Zn- and Mn-SOD activity (P < 0.001) and in Cu/Zn-SOD transcript (P < 0.001) and its protein (P < 0.05) were found in cataractous lenses. No significant change in the level of copper (P = 0.36) and an increase in the level of manganese (P = 0.01) and zinc (P = 0.02) were observed in cataractous lenses. A significant positive correlation between the level of Cu/Zn-SOD activity and the levels of Cu (P = 0.003) and Zn (P = 0.005) was found in the cataractous lenses. DNA sequencing revealed three intronic INDEL variations in exon4 of SOD1 gene. Splice-junction analysis showed the potential of IVS4+42delG in creating a new cryptic acceptor site. If it is involved in alternate splicing, it could result in generation of SOD1 mRNA transcripts lacking exon4 region. Transcript analysis revealed the presence of complete SOD1 mRNA transcripts. Genotyping revealed the presence of IVS4+42delG polymorphism in all subjects. Conclusions. The decrease in the activity of SOD1 isoform in cataractous lenses was associated with the decreased level of mRNA transcripts and their protein expression and was not associated with either modulation in the level of enzyme cofactors or with INDEL variations. PMID:23970468

Combined proteomic and molecular approaches for cloning and characterization of copper-zinc superoxide dismutase (Cu, Zn-SOD2) from garlic (Allium sativum).

PubMed

Hadji Sfaxi, Imen; Ezzine, Aymen; Coquet, Laurent; Cosette, Pascal; Jouenne, Thierry; Marzouki, M Nejib

2012-09-01

Superoxide dismutases (SODs; EC 1.15.1.1) are key enzymes in the cells protection against oxidant agents. Thus, SODs play a major role in the protection of aerobic organisms against oxygen-mediated damages. Three SOD isoforms were previously identified by zymogram staining from Allium sativum bulbs. The purified Cu, Zn-SOD2 shows an antagonist effect to an anticancer drug and alleviate cytotoxicity inside tumor cells lines B16F0 (mouse melanoma cells) and PAE (porcine aortic endothelial cells). To extend the characterization of Allium SODs and their corresponding genes, a proteomic approach was applied involving two-dimensional gel electrophoresis and LC-MS/MS analyses. From peptide sequence data obtained by mass spectrometry and sequences homologies, primers were defined and a cDNA fragment of 456 bp was amplified by RT-PCR. The cDNA nucleotide sequence analysis revealed an open reading frame coding for 152 residues. The deduced amino acid sequence showed high identity (82-87%) with sequences of Cu, Zn-SODs from other plant species. Molecular analysis was achieved by a protein 3D structural model.

Characterization of the Bacillus stearothermophilus manganese superoxide dismutase gene and its ability to complement copper/zinc superoxide dismutase deficiency in Saccharomyces cerevisiae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowler, C.; Inze, D.; Van Camp, W.

1990-03-01

Recombinant clones containing the manganese superoxide dismutase (MnSOD) gene of Bacillus stearothermophilus were isolated with an oligonucleotide probe designed to match a part of the previously determined amino acid sequence. Complementation analyses, performed by introducing each plasmid into a superoxide dismutase-deficient mutant of Escherichia coli, allowed us to define the region of DNA which encodes the MnSOD structural gene and to identify a promoter region immediately upstream from the gene. These data were subsequently confirmed by DNA sequencing. Since MnSOD is normally restricted to the mitochondria in eucaryotes, we were interested (i) in determining whether B. stearothermophilus MnSOD could functionmore » in eucaryotic cytosol and (ii) in determining whether MnSOD could replace the structurally unrelated copper/zinc superoxide dismutase (Cu/ZnSOD) which is normally found there. To test this, the sequence encoding bacterial MnSOD was cloned into a yeast expression vector and subsequently introduced into a Cu/ZnSOD-deficient mutant of the yeast Saccharomyces cerevisiae. Functional expression of the protein was demonstrated, and complementation tests revealed that the protein was able to provide tolerance at wild-type levels to conditions which are normally restrictive for this mutant. Thus, in spite of the evolutionary unrelatedness of these two enzymes, Cu/ZnSOD can be functionally replaced by MnSOD in yeast cytosol.« less

Flexibility of the Cu,Zn superoxide dismutase structure investigated at 0.57 GPa.

PubMed

Ascone, Isabella; Savino, Carmelinda; Kahn, Richard; Fourme, Roger

2010-06-01

The 2 A resolution crystal structure of bovine erythrocyte Cu,Zn superoxide dismutase (CuZnSOD) has been determined by X-ray diffraction at high pressure (0.57 GPa) and room temperature. At 0.57 GPa the secondary, tertiary and quaternary structures are similar to other previously determined bovine erythrocyte CuZnSOD structures. Nevertheless, pressure has a localized impact on the atomic coordinates of C(alpha) atoms and on side chains. The compression of the crystal and of the protein backbone is anisotropic. This anisotropy is discussed, taking into account intermolecular contacts and protein conformation. Pressure perturbation highlights the more flexible zones in the protein such as the electrostatic loop. At 0.57 GPa, a global shift of the dimetallic sites in both subunits and changes in the oxidation state of Cu were observed. The flexibility of the electrostatic loop may be useful for the interaction of different metal carriers in the copper-uptake process, whereas the flexibility of the metal sites involved in the activity of the protein could contribute to explaining the ubiquitous character of CuZnSODs, which are found in organisms living in very different conditions, including the deep-sea environment. This work illustrates the potential of combining X-ray crystallography with high pressure to promote and stabilize higher energy conformational substates.

Distinct oxidative cleavage and modification of bovine [Cu-Zn]-SOD by an ascorbic acid/Cu(II) system: Identification of novel copper binding site on SOD molecule

PubMed Central

Uehara, Hiroshi; Luo, Shen; Aryal, Baikuntha; Levine, Rodney L.; Rao, V. Ashutosh

2016-01-01

We investigated the combined effect of ascorbate and copper [Asc/Cu(II)] on the integrity of bovine [Cu-Zn]-superoxide dismutase (bSOD1) as a model system to study the metal catalyzed oxidation (MCO) and fragmentation of proteins. We found Asc/Cu(II) mediates specific cleavage of bSOD1 and generates 12.5 and 3.2 kDa fragments in addition to oxidation/carbonylation of the protein. The effect of other tested transition metals, a metal chelator, and hydrogen peroxide on the cleavage and oxidation indicated that binding of copper to a previously unknown site on SOD1 is responsible for the Asc/Cu(II) specific cleavage and oxidation. We utilized tandem mass spectrometry to identify the specific cleavage sites of Asc/Cu(II)-treated bSOD1. Analyses of tryptic- and AspN-peptides have demonstrated the cleavage to occur at Gly31 with peptide bond breakage with Thr30 and Ser32 through diamide and α-amidation pathways, respectively. The three-dimensional structure of bSOD1 reveals the imidazole ring of His19 localized within 5 Angstrom from the α-carbon of Gly31 providing a structural basis that copper ion, most likely coordinated by His19, catalyzes the specific cleavage reaction. PMID:26872685

Distinct oxidative cleavage and modification of bovine [Cu- Zn]-SOD by an ascorbic acid/Cu(II) system: Identification of novel copper binding site on SOD molecule.

PubMed

Uehara, Hiroshi; Luo, Shen; Aryal, Baikuntha; Levine, Rodney L; Rao, V Ashutosh

2016-05-01

We investigated the combined effect of ascorbate and copper [Asc/Cu(II)] on the integrity of bovine [Cu-Zn]-superoxide dismutase (bSOD1) as a model system to study the metal catalyzed oxidation (MCO) and fragmentation of proteins. We found Asc/Cu(II) mediates specific cleavage of bSOD1 and generates 12.5 and 3.2kDa fragments in addition to oxidation/carbonylation of the protein. The effect of other tested transition metals, a metal chelator, and hydrogen peroxide on the cleavage and oxidation indicated that binding of copper to a previously unknown site on SOD1 is responsible for the Asc/Cu(II) specific cleavage and oxidation. We utilized tandem mass spectrometry to identify the specific cleavage sites of Asc/Cu(II)-treated bSOD1. Analyses of tryptic- and AspN-peptides have demonstrated the cleavage to occur at Gly31 with peptide bond breakage with Thr30 and Ser32 through diamide and α-amidation pathways, respectively. The three-dimensional structure of bSOD1 reveals the imidazole ring of His19 localized within 5Å from the α-carbon of Gly31 providing a structural basis that copper ion, most likely coordinated by His19, catalyzes the specific cleavage reaction. Published by Elsevier Inc.

Relationship of ROS accumulation and superoxide dismutase isozymes in developing anther with floret fertility of rice under heat stress.

PubMed

Zhao, Qian; Zhou, Lujian; Liu, Jianchao; Du, Xiaoxia; Asad, Muhammad-Asad-Ullah; Huang, Fudeng; Pan, Gang; Cheng, Fangmin

2018-01-01

High temperature (HT) at meiosis stage is one of most important environment constraint affecting spikelet fertility and rice yield. In this paper, the effects of HT exposure at meiosis stage on the ROS (reactive oxygen species) accumulation, various superoxide dismutase (SOD, EC1.15.1.11) isozymes in developing anther, and its relationship with HT-induced decline in pollen viability and floret fertility were investigated by using four rice cultivars differing in heat tolerance under well-controlled climatic condition. Results showed that HT exposure significantly increased ROS level and malondialdehyde (MDA) content in rice anther, and this occurrence was strongly responsible for the HT-induced decline in pollen viability and harmful effect of HT adversity on floret fertility. However, the increased extent of ROS concentration in rice anther under HT exposure was greatly variable, depending on both the intensity and duration of HT exposure and different rice cultivars used. The SOD and CAT activities of HT-sensitive cultivars decreased more profoundly than those of HT-tolerant cultivars under the same HT regimes. Among various types of SOD enzymes, Cu/Zn-SODa expressed highly in rice anther and responded sensitively to HT exposure, while Cu/Zn-SODb expressed weakly in rice anther and preferentially in rice leaves. HT exposure suppressed the expression of Cu/Zn-SODa in developing anther, which was closely associated with the down-regulated transcripts of cCu/Zn-SOD1 gene. Hence, Cu/Zn-SODa may play a central role in the regulation of total SOD activity and ROS detoxification in rice anther as affected by HT exposure at meiosis stage. Copyright © 2017. Published by Elsevier Masson SAS.

Antioxidant defenses of Onychostoma macrolepis in response to thermal stress: Insight from mRNA expression and activity of superoxide dismutase and catalase.

PubMed

Yu, Haibo; Deng, Wei; Zhang, Dongdong; Gao, Yao; Yang, Zhou; Shi, Xiaochen; Sun, Jian; Zhou, Jishu; Ji, Hong

2017-07-01

Onychostoma macrolepis has becoming an endangered fish species in China, which population gradually declined in the past few decades due to the changing environment including elevated water temperature resulted from adverse weather events. The present study determined antioxidant defenses of O. macrolepis in response to thermal stress, aiming to understand the role of antioxidant system in adaptation of thermal stress for O. macrolepis. Experimental fish which were acclimated at 24 °C were stressed at 30 °C for 0 h, 1 h, 3 h, 6 h, 12 h, 24 h and 48 h, respectively. Change in mRNA expression of Cu/Zn superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) and activity of SOD and CAT of the experimental fish with different stress time were determined. We cloned the full-length cDNA of Cu/Zn-SOD and CAT by means of RACE method, and analyzed their molecular characterization and tissue distribution. We discovered that the mRNA expression of the Cu/Zn-SOD in heart, liver, spleen, gill, intestine and the CAT in heart, liver, spleen, kidney, intestine and muscle of O. macrolepis significantly increased when water temperature increased from 24 °C to 30 °C, indicating a sensitive response of mRNA expression of Cu/Zn-SOD and CAT to the thermal stress. Moreover, the mRNA expression of the Cu/Zn-SOD and CAT were varied in different tissues, indicating different sensitivity of the tissues in response to thermal stress. Activity of the SOD in serum of O. macrolepis gradually increased from 1 h to 12 h sampling time, but significantly decreased at 24 h sampling time, compared to that of 0 h sampling time. And activity of the CAT in serum of O. macrolepis significantly decreased from 1 h to 12 h sampling time, and did not changed significantly at 24 h and 48 h sampling time, compared to that of 0 h sampling time. As such, MDA contents in the serum of O. macrolepis significantly decreased from 1 h to 6 h sampling time, but significantly increased at 12 h and 24 h sampling time, compared to that of 0 h sampling time. In summary, antioxidant system of the O. macrolepis can quickly response to short term thermal stress at 30 °C in form of both the mRNA expression of Cu/Zn-SOD and CAT and the activity of SOD and CAT, and consequently enhance the antioxidant defenses of O. macrolepis. However, thermal stress at 30 °C for 12 h-24 h seems to lead to oxidative damage of the O. macrolepis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of Whole Body SOD1 Knockout with Muscle-Specific SOD1 Knockout Mice Reveals a Role for Nerve Redox Signaling in Regulation of Degenerative Pathways in Skeletal Muscle.

PubMed

Sakellariou, Giorgos K; McDonagh, Brian; Porter, Helen; Giakoumaki, Ifigeneia I; Earl, Kate E; Nye, Gareth A; Vasilaki, Aphrodite; Brooks, Susan V; Richardson, Arlan; Van Remmen, Holly; McArdle, Anne; Jackson, Malcolm J

2018-02-01

Lack of Cu,Zn-superoxide dismutase (CuZnSOD) in homozygous knockout mice (Sod1 -/- ) leads to accelerated age-related muscle loss and weakness, but specific deletion of CuZnSOD in skeletal muscle (mSod1KO mice) or neurons (nSod1KO mice) resulted in only mild muscle functional deficits and failed to recapitulate the loss of mass and function observed in Sod1 -/- mice. To dissect any underlying cross-talk between motor neurons and skeletal muscle in the degeneration in Sod1 -/- mice, we characterized neuromuscular changes in the Sod1 -/- model compared with mSod1KO mice and examined degenerative molecular mechanisms and pathways in peripheral nerve and skeletal muscle. In contrast to mSod1KO mice, myofiber atrophy in Sod1 -/- mice was associated with increased muscle oxidative damage, neuromuscular junction degeneration, denervation, nerve demyelination, and upregulation of proteins involved in maintenance of myelin sheaths. Proteomic analyses confirmed increased proteasomal activity and adaptive stress responses in muscle of Sod1 -/- mice that were absent in mSod1KO mice. Peripheral nerve from neither Sod1 -/- nor mSod1KO mice showed increased oxidative damage or molecular responses to increased oxidation compared with wild type mice. Differential cysteine (Cys) labeling revealed a specific redox shift in the catalytic Cys residue of peroxiredoxin 6 (Cys47) in the peripheral nerve from Sod1 -/- mice. Innovation and Conclusion: These findings demonstrate that neuromuscular integrity, redox mechanisms, and pathways are differentially altered in nerve and muscle of Sod1 -/- and mSod1KO mice. Results support the concept that impaired redox signaling, rather than oxidative damage, in peripheral nerve plays a key role in muscle loss in Sod1 -/- mice and potentially sarcopenia during aging. Antioxid. Redox Signal. 28, 275-295.

Chronopharmacological effects of growth hormone on the executive function and oxidative stress response in rats.

PubMed

Ferrari, Carlos K B; França, Eduardo L; Monteiro, Luciane A; Santos, Bruno L; Pereira-Junior, Alfredo; Honorio-França, Adenilda C

2017-01-01

To investigate the chronopharmacological effects of growth hormone on executive function and the oxidative stress response in rats. Fifty male Wistar rats (36-40 weeks old) had ad libitum access to water and food and were separated into four groups: diurnal control, nocturnal control, diurnal GH-treated, and nocturnal GH-treated animals. Levels of Cu, Zn superoxide dismutase (Cu, Zn-SOD), and superoxide release by spleen macrophages were evaluated. For memory testing, adaptation and walking in an open field platform was used. GH-treated animals demonstrated better performance in exploratory and spatial open-field tests. The latency time in both GH-treated groups was significantly lower compared with the latency time of the control groups. The diurnal GH treatment did not stimulate superoxide release but increased the CuZn-SOD enzyme levels. The nocturnal GH treatment did not influence the superoxide release and CuZn-SOD concentration. GH treatment also resulted in heart atrophy and lung hypertrophy. Growth hormone treatment improved the performance of executive functions at the cost of oxidative stress triggering, and this effect was dependent on the circadian period of hormone administration. However, GH treatment caused damaging effects such as lung hypertrophy and heart atrophy.

The Megavirus Chilensis Cu,Zn-Superoxide Dismutase: the First Viral Structure of a Typical Cellular Copper Chaperone-Independent Hyperstable Dimeric Enzyme

PubMed Central

Lartigue, Audrey; Burlat, Bénédicte; Coutard, Bruno; Chaspoul, Florence; Claverie, Jean-Michel

2014-01-01

ABSTRACT Giant viruses able to replicate in Acanthamoeba castellanii penetrate their host through phagocytosis. After capsid opening, a fusion between the internal membranes of the virion and the phagocytic vacuole triggers the transfer in the cytoplasm of the viral DNA together with the DNA repair enzymes and the transcription machinery present in the particles. In addition, the proteome analysis of purified mimivirus virions revealed the presence of many enzymes meant to resist oxidative stress and conserved in the Mimiviridae. Megavirus chilensis encodes a predicted copper, zinc superoxide dismutase (Cu,Zn-SOD), an enzyme known to detoxify reactive oxygen species released in the course of host defense reactions. While it was thought that the metal ions are required for the formation of the active-site lid and dimer stabilization, megavirus chilensis SOD forms a very stable metal-free dimer. We used electron paramagnetic resonance (EPR) analysis and activity measurements to show that the supplementation of the bacterial culture with copper and zinc during the recombinant expression of Mg277 is sufficient to restore a fully active holoenzyme. These results demonstrate that the viral enzyme's activation is independent of a chaperone both for disulfide bridge formation and for copper incorporation and suggest that its assembly may not be as regulated as that of its cellular counterparts. A SOD protein is encoded by a variety of DNA viruses but is absent from mimivirus. As in poxviruses, the enzyme might be dispensable when the virus infects Acanthamoeba cells but may allow megavirus chilensis to infect a broad range of eukaryotic hosts. IMPORTANCE Mimiviridae are giant viruses encoding more than 1,000 proteins. The virion particles are loaded with proteins used by the virus to resist the vacuole's oxidative stress. The megavirus chilensis virion contains a predicted copper, zinc superoxide dismutase (Cu,Zn-SOD). The corresponding gene is present in some megavirus chilensis relatives but is absent from mimivirus. This first crystallographic structure of a viral Cu,Zn-SOD highlights the features that it has in common with and its differences from cellular SODs. It corresponds to a very stable dimer of the apo form of the enzyme. We demonstrate that upon supplementation of the growth medium with Cu and Zn, the recombinant protein is fully active, suggesting that the virus's SOD activation is independent of a copper chaperone for SOD generally used by eukaryotic SODs. PMID:25355875

Dietary Manganese Modulates PCB126 Toxicity, Metal Status, and MnSOD in the Rat

PubMed Central

Wang, Bingxuan; Klaren, William D.; Wels, Brian R.; Simmons, Donald L.; Olivier, Alicia K.; Wang, Kai; Robertson, Larry W.; Ludewig, Gabriele

2016-01-01

PCB126 (3,3′,4,4′,5-pentachlorobiphenyl) is a potent aryl hydrocarbon receptor agonist and induces oxidative stress. Because liver manganese (Mn) levels decrease in response to PCB126, a Mn dietary study was designed to investigate the role of Mn in PCB126 toxicity. Male Sprague Dawley rats received diets containing 0, 10, or 150 ppm added Mn for 3 weeks, followed by a single ip injection of corn oil or PCB126 (5 µmol/kg body weight). After 2 weeks, Mn, Cu, Zn, and Fe levels in the heart, liver, and liver mitochondria, and Mn-containing superoxide dismutase (MnSOD) and metallothionein mRNA, MnSOD protein, and MnSOD activity were determined. Mn levels in liver, heart, and liver mitochondria were strongly decreased by the Mn-deficient diet. Small effects on Fe levels and a stepwise increase in MnSOD activity with dietary Mn were also visible. PCB126 caused profound changes in Cu (up), Zn, Fe, and Mn (down) in liver, but not in heart, and differing effects (Cu, Zn, and Fe up, Mn down) in liver mitochondria. Liver MnSOD and metallothionein mRNA levels and MnSOD protein were increased but MnSOD activity was decreased by PCB126. PCB126-induced liver enlargement was dose-dependently reduced with increasing dietary Mn. These changes in metals homeostasis and MnSOD activity in liver but not heart may be a/the mechanism of PCB126 liver-specific toxicity. Specifically, transport of Fenton metals (Cu, Fe) into and Mn out of the mitochondria, a probable mechanism for lower MnSOD activity, may be a/the cause of PCB126-induced oxidative stress. The role of metallothioneins needs further evaluation. Dietary Mn slightly alleviated PCB126-induced toxicities. PMID:26660635

Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis.

PubMed

Roberts, Blaine R; Lim, Nastasia K H; McAllum, Erin J; Donnelly, Paul S; Hare, Dominic J; Doble, Philip A; Turner, Bradley J; Price, Katherine A; Lim, Sin Chun; Paterson, Brett M; Hickey, James L; Rhoads, Timothy W; Williams, Jared R; Kanninen, Katja M; Hung, Lin W; Liddell, Jeffrey R; Grubman, Alexandra; Monty, Jean-Francois; Llanos, Roxana M; Kramer, David R; Mercer, Julian F B; Bush, Ashley I; Masters, Colin L; Duce, James A; Li, Qiao-Xin; Beckman, Joseph S; Barnham, Kevin J; White, Anthony R; Crouch, Peter J

2014-06-04

Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper(II) [Cu(II)(atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with Cu(II)(atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of fully metallated (holo) SOD1. Tracking isotopically enriched (65)Cu(II)(atsm) confirmed the increase in holo-SOD1 involved transfer of Cu from Cu(II)(atsm) to SOD1, suggesting the improved locomotor function and survival of the Cu(II)(atsm)-treated SOD1G37R mice involved, at least in part, the ability of the compound to improve the Cu content of the mutant SOD1. This was supported by improved survival of SOD1G37R mice that expressed the human gene for the Cu uptake protein CTR1. Improving the metal content of mutant SOD1 in vivo with Cu(II)(atsm) did not decrease levels of misfolded SOD1. These outcomes indicate the metal content of SOD1 may be a greater determinant of the toxicity of the protein in mutant SOD1-associated forms of ALS than the mutations themselves. Improving the metal content of SOD1 therefore represents a valid therapeutic strategy for treating ALS caused by SOD1. Copyright © 2014 the authors 0270-6474/14/348021-11$15.00/0.

Sleep deprivation alters gene expression and antioxidant enzyme activity in mice splenocytes.

PubMed

Lungato, L; Marques, M S; Pereira, V G; Hix, S; Gazarini, M L; Tufik, S; D'Almeida, V

2013-03-01

Cellular defence against the formation of reactive oxygen species (ROS) involves a number of mechanisms in which antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) play an important role. The relation between sleep deprivation and oxidative stress has not yet been completely elucidated. Although some authors did not find evidence of this relationship, others found alterations in some oxidative stress markers in response to sleep deprivation. Thus, the objective of this study was to identify changes induced by sleep deprivation in the activity and gene expression of antioxidant enzymes in mice splenocytes, ideally corroborating a better understanding of the observed effects related to sleep deprivation, which could be triggered by oxidative imbalance. Splenocytes from mice sleep deprived for 72 h showed no significant difference in CAT and CuZnSOD gene expression compared with normal sleep mice. However, sleep-deprived mice did show higher MnSOD gene expression than the control group. Concerning enzymatic activity, CuZnSOD and MnSOD significantly increased after sleep deprivation, despite the expression in CuZnSOD remained unchanged. Moreover, CAT activity was significantly lower after sleep deprivation. The data suggest that the antioxidant system is triggered by sleep deprivation, which in turn could influence the splenocytes homoeostasis, thus interfering in physiological responses. © 2013 The Authors. Scandinavian Journal of Immunology © 2013 Blackwell Publishing Ltd.

Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death.

PubMed

Choi, Soo Hyun; Kim, Dae Won; Kim, So Young; An, Jae Jin; Lee, Sun Hwa; Choi, Hee Soon; Sohn, Eun Jung; Hwang, Seok-Il; Won, Moo Ho; Kang, Tae-Cheon; Kwon, Hyung Joo; Kang, Jung Hoon; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2005-12-31

Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.

Imaging of glial cell morphology, SOD1 distribution and elemental composition in the brainstem and hippocampus of the ALS hSOD1G93A rat.

PubMed

Stamenković, Stefan; Dučić, Tanja; Stamenković, Vera; Kranz, Alexander; Andjus, Pavle R

2017-08-15

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor and cognitive domains of the CNS. Mutations in the Cu,Zn-superoxide dismutase (SOD1) cause 20% of familial ALS and provoke formation of intracellular aggregates and copper and zinc unbinding, leading to glial activation and neurodegeneration. Therefore, we investigated glial cell morphology, intracellular SOD1 distribution, and elemental composition in the brainstem and hippocampus of the hSOD1 G93A transgenic rat model of ALS. Immunostaining for astrocytes, microglia and SOD1 revealed glial proliferation and progressive tissue accumulation of SOD1 in both brain regions of ALS rats starting already at the presymptomatic stage. Glial cell morphology analysis in the brainstem of ALS rats revealed astrocyte activation occurring before disease symptoms onset, followed by activation of microglia. Hippocampal ALS astrocytes exhibited an identical reactive profile, while microglial morphology was unchanged. Additionally, ALS brainstem astrocytes demonstrated progressive SOD1 accumulation in the cell body and processes, while microglial SOD1 levels were reduced and its distribution limited to distal cell processes. In the hippocampus both glial cell types exhibited SOD1 accumulation in the cell body. X-ray fluorescence imaging revealed decreased P and increased Ca, Cl, K, Ni, Cu and Zn in the brainstem, and higher levels of Cl, Ni and Cu, but lower levels of Zn in the hippocampus of symptomatic ALS rats. These results bring new insights into the glial response during disease development and progression in motor as well as in non-motor CNS structures, and indicate disturbed tissue elemental homeostasis as a prominent hallmark of disease pathology. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Superoxide dismutase from Trichuris ovis--inhibition by benzimidazoles and pyrimidine derivatives.

PubMed

Sanchez-Moreno, M; Garcia-Rejon, L; Salas, I; Osuna, A; Monteoliva, M

1992-01-01

Three superoxide dismutase isoenzymes of different cellular location were detected in an homogenate of Trichuris ovis. Each of these molecular forms was purified by differential centrifugation and precipitation with ammonium sulphate, followed by chromatography on DEAE-cellulose and Sephadex G-75 columns. The activity levels of the two molecular forms detected in the mitochondrial (one cyanide sensitive Cu-Zn-SOD and the other cyanide insensitive Mn-SOD) were higher than that of the superoxide dismutase detected in the cytoplasmic fraction (cyanide sensitive Cu-Zn-SOD). All molecular forms present evident differences to the SODs contained in the host liver. Molecular mass and some of the physical and chemical properties of the enzyme was determined for all three molecular forms. An inhibitory effect on the SOD of the parasite an the host was detected with a series of compounds, some of which markedly inhibited parasite enzyme but not host enzyme.

Enhanced Reactive Oxygen Species Scavenging by Overproduction of Superoxide Dismutase and Catalase Delays Postharvest Physiological Deterioration of Cassava Storage Roots1[C][W][OA

PubMed Central

Xu, Jia; Duan, Xiaoguang; Yang, Jun; Beeching, John R.; Zhang, Peng

2013-01-01

Postharvest physiological deterioration (PPD) of cassava (Manihot esculenta) storage roots is the result of a rapid oxidative burst, which leads to discoloration of the vascular tissues due to the oxidation of phenolic compounds. In this study, coexpression of the reactive oxygen species (ROS)-scavenging enzymes copper/zinc superoxide dismutase (MeCu/ZnSOD) and catalase (MeCAT1) in transgenic cassava was used to explore the intrinsic relationship between ROS scavenging and PPD occurrence. Transgenic cassava plants integrated with the expression cassette p54::MeCu/ZnSOD-35S::MeCAT1 were confirmed by Southern-blot analysis. The expression of MeCu/ZnSOD and MeCAT1 was verified by quantitative reverse transcription-polymerase chain reaction and enzymatic activity analysis both in the leaves and storage roots. Under exposure to the ROS-generating reagent methyl viologen or to hydrogen peroxide (H2O2), the transgenic plants showed higher enzymatic activities of SOD and CAT than the wild-type plants. Levels of malondialdehyde, chlorophyll degradation, lipid peroxidation, and H2O2 accumulation were dramatically reduced in the transgenic lines compared with the wild type. After harvest, the storage roots of transgenic cassava lines show a delay in their PPD response of at least 10 d, accompanied by less mitochondrial oxidation and H2O2 accumulation, compared with those of the wild type. We hypothesize that this is due to the combined ectopic expression of Cu/ZnSOD and CAT leading to an improved synergistic ROS-scavenging capacity of the roots. Our study not only sheds light on the mechanism of the PPD process but also develops an effective approach for delaying the occurrence of PPD in cassava. PMID:23344905

Enhanced reactive oxygen species scavenging by overproduction of superoxide dismutase and catalase delays postharvest physiological deterioration of cassava storage roots.

PubMed

Xu, Jia; Duan, Xiaoguang; Yang, Jun; Beeching, John R; Zhang, Peng

2013-03-01

Postharvest physiological deterioration (PPD) of cassava (Manihot esculenta) storage roots is the result of a rapid oxidative burst, which leads to discoloration of the vascular tissues due to the oxidation of phenolic compounds. In this study, coexpression of the reactive oxygen species (ROS)-scavenging enzymes copper/zinc superoxide dismutase (MeCu/ZnSOD) and catalase (MeCAT1) in transgenic cassava was used to explore the intrinsic relationship between ROS scavenging and PPD occurrence. Transgenic cassava plants integrated with the expression cassette p54::MeCu/ZnSOD-35S::MeCAT1 were confirmed by Southern-blot analysis. The expression of MeCu/ZnSOD and MeCAT1 was verified by quantitative reverse transcription-polymerase chain reaction and enzymatic activity analysis both in the leaves and storage roots. Under exposure to the ROS-generating reagent methyl viologen or to hydrogen peroxide (H2O2), the transgenic plants showed higher enzymatic activities of SOD and CAT than the wild-type plants. Levels of malondialdehyde, chlorophyll degradation, lipid peroxidation, and H2O2 accumulation were dramatically reduced in the transgenic lines compared with the wild type. After harvest, the storage roots of transgenic cassava lines show a delay in their PPD response of at least 10 d, accompanied by less mitochondrial oxidation and H2O2 accumulation, compared with those of the wild type. We hypothesize that this is due to the combined ectopic expression of Cu/ZnSOD and CAT leading to an improved synergistic ROS-scavenging capacity of the roots. Our study not only sheds light on the mechanism of the PPD process but also develops an effective approach for delaying the occurrence of PPD in cassava.

Time- and dose-dependent differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase enzymatic activity and mRNA level by vitamin E in rat blood cells.

PubMed

Hajiani, Maliheh; Razi, Farideh; Golestani, Aboualfazl; Frouzandeh, Mehdi; Owji, Ali Akbar; Khaghani, Shahnaz; Ghannadian, Naghmeh; Shariftabrizi, Ahmad; Pasalar, Parvin

2012-01-01

Vitamin E is the most important lipid-soluble antioxidant. Recently, it has been proposed as a gene regulator, and its gene modulation effects have been observed at different levels of gene expression and cell signaling. This study was performed to investigate the effects of vitamin E on the activity and expression of the most important endogenous antioxidant enzyme, superoxide dismutase (SOD), in rat plasma. Twenty-eight male Sprauge-Dawley rats were divided into four groups: control group and three dosing groups. The control group received the vehicle (liquid paraffin), and the dosing groups received twice-weekly intraperitoneal injections of 10, 30, and 100 mg/kg of vitamin E ((±)-α-Tocopherol) for 6 weeks. Quantitative real-time reverse transcription-polymerase chain reaction and enzyme assays were used to assess the levels of Cu/Zn-SOD and Mn-SOD mRNA and enzyme activity levels in blood cells at 0, 2, 4, and 6 weeks following vitamin E administration. Catalase enzyme activity and total antioxidant capacity were also assessed in plasma at the same time intervals. Mn-SOD activity was significantly increased in the 100 and 30 mg/kg dosing groups after 4 and 6 weeks, with corresponding significant increase in their mRNA levels. Cu/Zn-SOD activity was not significantly changed in response to vitamin E administration at any time points, whereas Cu/Zn-SOD mRNA levels were significantly increased after longer time points with high doses (30 and 100 mg/kg) of vitamin E. Catalase enzyme activity was transiently but significantly increased after 4 weeks of vitamin E treatment in 30 and 100 mg/kg dosing groups. Total antioxidant status was significantly increased after 4 and 6 weeks in the 100 mg/kg dosing group. Only the chronic administration of higher doses of alpha-tocopherol is associated with the increased activity and expression of Mn-SOD in rats. Cu/Zn-SOD activity and expression does not dramatically change in response to vitamin E.

Effects of Zinc Glycinate on Productive and Reproductive Performance, Zinc Concentration and Antioxidant Status in Broiler Breeders.

PubMed

Zhang, Ling; Wang, Yong-Xia; Xiao, Xue; Wang, Jiang-Shui; Wang, Qian; Li, Kai-Xuan; Guo, Tian-Yu; Zhan, Xiu-An

2017-08-01

An experiment was conducted to investigate the effects of zinc glycinate (Zn-Gly) supplementation as an alternative for zinc sulphate (ZnSO 4 ) on productive and reproductive performance, zinc (Zn) concentration and antioxidant status in broiler breeders. Six hundred 39-week-old Lingnan Yellow broiler breeders were randomly assigned to 6 groups consisting of 4 replicates with 25 birds each. Breeders were fed a basal diet (control group, 24 mg Zn/kg diet), basal diet supplemented with 80 mg Zn/kg diet from ZnSO 4 or basal diet supplemented with 20, 40, 60 and 80 mg Zn/kg diet from Zn-Gly. The experiment lasted for 8 weeks after a 4-week pre-test with the basal diet, respectively. Results showed that Zn supplementation, regardless of sources, improved (P < 0.05) the feed conversion ratio (kilogram of feed/kilogram of egg) and decreased broken egg rate, and elevated (P < 0.05) the qualified chick rate. Compared with the ZnSO 4 group, the 80 mg Zn/kg Zn-Gly group significantly increased (P < 0.05) average egg weight, fertility, hatchability and qualified chick rate, whereas it decreased (P < 0.05) broken egg rate. The Zn concentrations in liver and muscle were significantly higher (P < 0.05) in 80 mg Zn/kg Zn-Gly group than that in ZnSO 4 group. Compared with ZnSO 4 group, 80 mg Zn/kg Zn-Gly group significantly elevated (P < 0.05) the mRNA abundances of metallothionein (MT) and copper-zinc superoxide (Cu-Zn SOD), as well as the Cu-Zn SOD activity and MT concentration in liver. Moreover, the 80 mg Zn/kg Zn-Gly group had higher (P < 0.05) serum T-SOD and Cu-Zn SOD activities than that in the ZnSO 4 group. This study indicated that supplementation of Zn in basal diet improved productive and reproductive performance, Zn concentration and antioxidant status in broiler breeders, and the 80 mg Zn/kg from Zn-Gly was the optimum choice for broiler breeders compared with other levels of Zn from Zn-Gly and 80 mg/kg Zn from ZnSO 4 .

Adaptive flexibility of enzymatic antioxidants SOD, APX and CAT to high light stress: The clonal perennial monocot Iris pumila as a study case.

PubMed

Vuleta, Ana; Manitašević Jovanović, Sanja; Tucić, Branka

2016-03-01

High solar radiation has been recognized as one of the main causes of the overproduction of reactive oxygen species (ROS) and oxidative stress in plants. To remove the excess of ROS, plants use different antioxidants and tune their activity and/or isoform number as required for given light conditions. In this study, the adaptiveness of light-induced variation in the activities and isoform patterns of key enzymatic antioxidants SOD, APX and CAT was tested in leaves of Iris pumila clonal plants from two natural populations inhabiting a sun exposed dune site and a forest understory, using a reciprocal-transplant experiment. At the exposed habitat, the mean enzymatic activity of total SODs was significantly greater than that in the shaded one, while the amount of the mitochondrial MnSOD was notably higher compared to the plastidic Cu/ZnSOD. However, the number of Cu/ZnSOD isoforms was greater in the forest understory relative to the exposed site (three vs. two, respectively). An inverse relationship recorded between the quantities of MnSOD and Cu/ZnSOD in alternative light habitats might indicate that the two enzymes compensate each other in maintaining intracellular ROS and redox balance. The adaptive population differentiation in APX activity was exclusively recorded in the open habitat, which indicated that the synergistic effect of high light and temperature stress could be the principal selective factor, rather than high light alone. The enzymatic activity of CAT was similar between the two populations, implicating APX as the primary H2O2 scavenger in the I. pumila leaves exposed to high light intensity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

DOE PAGES

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; ...

2015-10-12

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

Modification of a single tryptophan residue in human Cu,Zn-superoxide dismutase by peroxynitrite in the presence of bicarbonate.

PubMed

Yamakura, F; Matsumoto, T; Fujimura, T; Taka, H; Murayama, K; Imai, T; Uchida, K

2001-07-09

Human recombinant Cu,Zn-SOD was reacted with peroxynitrite in a reaction mixture containing 150 mM potassium phosphate buffer (pH 7.4) 25 mM sodium bicarbonate, and 0.1 mM diethylenetriamine pentaacetic acid. Disappearance of fluorescence emission at 350 nm, which could be attributed to modification of a single tryptophan residue, was observed in the modified enzyme with a pH optimum of around 8.4. A fluorescence decrease with the same pH optimum was also observed without sodium bicarbonate, but with less efficiency. Amino acid contents of the modified enzyme showed no significant difference in all amino acids except the loss of a single tryptophan residue of the enzyme. The peroxynitrite-modified enzyme showed an increase in optical absorption around 350 nm and 30% reduced enzyme activity based on the copper contents. The modified enzyme showed the same electron paramagnetic resonance spectrum as that of the control enzyme. The modified Cu,Zn-SOD showed a single protein band in sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS--PAGE) and five protein bands in non-denaturing PAGE. From this evidence, we conclude that nitration and/or oxidation of the single tryptophan 32 and partial inactivation of the enzyme activity of Cu,Zn-SOD is caused by a peroxynitrite-carbon dioxide adduct without perturbation of the active site copper integrity.

Purification of Cu/Zn superoxide dismutase from Piper betle leaf and its characterization in the oral cavity.

PubMed

Liu, Yu-Ching; Lee, Miau-Rong; Chen, Chao-Jung; Lin, Yung-Chang; Ho, Heng-Chien

2015-03-04

The aim of this study was to purify protein(s) from Piper betle leaf for identification and further characterization. A functionally unknown protein was purified to apparent homogeneity with a molecular mass of 15.7 kDa and identified as Cu/Zn superoxide dismutase (SOD). The purified SOD appeared to be monomeric and converted to its dimeric form with increased enzymatic activity in betel nut oral extract. This irreversible conversion was mainly induced by slaked lime, resulting from the increase in pH of the oral cavity. Oral extract from chewing areca nut alone also induced SOD dimerization due to the presence of arginine. The enhanced activity of the SOD dimer was responsible for the continuous production of hydrogen peroxide in the oral cavity. Thus, SOD may contribute to oral carcinogenesis through the continuous formation of hydrogen peroxide in the oral cavity, in spite of its protective role against cancer in vivo.

Non-native Soluble Oligomers of Cu/Zn Superoxide Dismutase (SOD1) Contain a Conformational Epitope Linked to Cytotoxicity in Amyotrophic Lateral Sclerosis (ALS)

PubMed Central

2015-01-01

Soluble misfolded Cu/Zn superoxide dismutase (SOD1) is implicated in motor neuron death in amyotrophic lateral sclerosis (ALS); however, the relative toxicities of the various non-native species formed by SOD1 as it misfolds and aggregates are unknown. Here, we demonstrate that early stages of SOD1 aggregation involve the formation of soluble oligomers that contain an epitope specific to disease-relevant misfolded SOD1; this epitope, recognized by the C4F6 antibody, has been proposed as a marker of toxic species. Formation of potentially toxic oligomers is likely to be exacerbated by an oxidizing cellular environment, as evidenced by increased oligomerization propensity and C4F6 reactivity when oxidative modification by glutathione is present at Cys-111. These findings suggest that soluble non-native SOD1 oligomers, rather than native-like dimers or monomers, share structural similarity to pathogenic misfolded species found in ALS patients and therefore represent potential cytotoxic agents and therapeutic targets in ALS. PMID:24660965

Nitric oxide activates superoxide dismutase and ascorbate peroxidase to repress the cell death induced by wounding.

PubMed

Lin, Chih-Ching; Jih, Pei-Ju; Lin, Hsin-Hung; Lin, Jeng-Shane; Chang, Ling-Lan; Shen, Yu-Hsing; Jeng, Shih-Tong

2011-10-01

Wounding caused by rain, wind, and pathogen may lead plants to onset defense response. Previous studies indicated that mechanical wounding stimulates plants to generate nitric oxide (NO) and hydrogen peroxide (H(2)O(2)). In this study, the functions of NO and H(2)O(2) after wounding in sweet potato (Ipomoea batatas cv. Tainung 57) was further analyzed. Mechanical wounding damaged cells and resulted in necrosis, but the presence of NO donors or NO scavenger might reduce or enhance the cell death caused by wounding, respectively. The amount of H(2)O(2) induced by wounding was also decreased or increased when plants were incubated with NO donors or NO scavenger, individually. These results indicate that NO may regulate H(2)O(2) generation to affect cell death. NO-induced proteins isolated from two-dimensional electrophoresis were identified to be Copper/Zinc superoxide dismutases (CuZnSODs). The activities of CuZnSODs and ascorbate peroxidase (APX) could be enhanced by NO. In addition, the expression of CuZnSOD and APX was induced by wounding via NO, and their expression was further stimulated by NO through the generation of cGMP. The influx of calcium ions and the activity of NADPH oxidase were also involved in the NO signal transduction pathway inducing APX expression. Collectively, the generation of H(2)O(2) in wounded plants might trigger cell death. Meanwhile, the production of NO induced by wounding stimulated signal transducers including cGMP, calcium ions, and H(2)O(2) to activate CuZnSOD and APX, which further decreased H(2)O(2) level and reduced the cell death caused by wounding.

Over-expression of copper/zinc superoxide dismutase in the median preoptic nucleus attenuates chronic angiotensin II-induced hypertension in the rat.

PubMed

Collister, John P; Bellrichard, Mitch; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C

2014-12-02

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·- in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2·- in the MnPO contributes to the development of chronic AngII-dependent hypertension.

Silicic Acid and Beer Consumption Reverses the Metal Imbalance and the Prooxidant Status Induced by Aluminum Nitrate in Mouse Brain.

PubMed

González-Muñoz, María José; Garcimartán, Alba; Meseguer, Isabel; Mateos-Vega, Carmen José; Orellana, José María; Peña-Fernández, Antonio; Benedí, Juana; Sánchez-Muniz, Francisco J

2017-01-01

Emerging evidence suggests that by affecting mineral balance, aluminum (Al) may enhance some events associated with neurodegenerative diseases. To examine the effect of Al(NO3)3 exposure on brain Al, cooper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), silicon (Si), and zinc (Zn) levels, and the metal-change implication in brain oxidant and inflammatory status. Four groups of six-week-old male NMRI mice were treated for three months: i) controls, administrated with deionized water; ii) Al, which received Al(NO3)3; iii) Al+silicic acid, which were given Al(NO3)3 plus silicic acid; and iv) Al+beer, which received Al(NO3)3 plus beer. Brain Al and TBARS levels and TNFα and GPx expressions increased, while Cu, Mn, and Zn levels, and catalase and CuZn-SOD expression decreased (at least, p < 0.05) in Al versus control animals. Al, Si, and TBARS levels and TNFα expression decreased (p < 0.05) in Al+silicic acid and Al+beer specimens while Cu, Mn, and Zn levels and antioxidant expression increased versus the Al group. Brain Al levels correlated negatively with those of Cu, Fe, Mn, and Zn, and catalase, CuZn-SOD, and GPx enzyme expressions but positively with Si and TBARS levels and TNFα expression. Two components of the principal component analysis (PCA) explained 71.2% of total data variance (p < 0.001). PCA connected the pro-oxidant markers with brain Al content, while brain Zn and Cu levels were closer to antioxidant enzyme expression. Administration of Al(NO3)3 induced metal imbalance, inflammation, and antioxidant status impairment in the brain. Those effects were blocked to a significant extent by silicic acid and beer administration.

Eukaryotic copper-only superoxide dismutases (SODs): A new class of SOD enzymes and SOD-like protein domains.

PubMed

Robinett, Natalie G; Peterson, Ryan L; Culotta, Valeria C

2018-03-30

The copper-containing superoxide dismutases (SODs) represent a large family of enzymes that participate in the metabolism of reactive oxygen species by disproportionating superoxide anion radical to oxygen and hydrogen peroxide. Catalysis is driven by the redox-active copper ion, and in most cases, SODs also harbor a zinc at the active site that enhances copper catalysis and stabilizes the protein. Such bimetallic Cu,Zn-SODs are widespread, from the periplasm of bacteria to virtually every organelle in the human cell. However, a new class of copper-containing SODs has recently emerged that function without zinc. These copper-only enzymes serve as extracellular SODs in specific bacteria ( i.e. Mycobacteria), throughout the fungal kingdom, and in the fungus-like oomycetes. The eukaryotic copper-only SODs are particularly unique in that they lack an electrostatic loop for substrate guidance and have an unusual open-access copper site, yet they can still react with superoxide at rates limited only by diffusion. Copper-only SOD sequences similar to those seen in fungi and oomycetes are also found in the animal kingdom, but rather than single-domain enzymes, they appear as tandem repeats in large polypeptides we refer to as CSRPs (copper-only SOD-repeat proteins). Here, we compare and contrast the Cu,Zn versus copper-only SODs and discuss the evolution of copper-only SOD protein domains in animals and fungi. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Increased expression of native cytosolic Cu/Zn superoxide dismutase and ascorbate peroxidase improves tolerance to oxidative and chilling stresses in cassava (Manihot esculenta Crantz)

PubMed Central

2014-01-01

Background Cassava (Manihot esculenta Crantz) is a tropical root crop, and is therefore, extremely sensitive to low temperature; its antioxidative response is pivotal for its survival under stress. Timely turnover of reactive oxygen species (ROS) in plant cells generated by chilling-induced oxidative damages, and scavenging can be achieved by non-enzymatic and enzymatic reactions in order to maintain ROS homeostasis. Results Transgenic cassava plants that co-express cytosolic superoxide dismutase (SOD), MeCu/ZnSOD, and ascorbate peroxidase (APX), MeAPX2, were produced and tested for tolerance against oxidative and chilling stresses. The up-regulation of MeCu/ZnSOD and MeAPX2 expression was confirmed by the quantitative reverse transcriptase-polymerase chain reaction, and enzymatic activity analyses in the leaves of transgenic cassava plant lines with a single-transgene integration site. Upon exposure to ROS-generating agents, 100 μM ROS-generating reagent methyl viologen and 0.5 M H2O2, higher levels of enzymatic activities of SOD and APX were detected in transgenic plants than the wild type. Consequently, the oxidative stress parameters, such as lipid peroxidation, chlorophyll degradation and H2O2 synthesis, were lower in the transgenic lines than the wild type. Tolerance to chilling stress at 4°C for 2 d was greater in transgenic cassava, as observed by the higher levels of SOD, catalase, and ascorbate-glutathione cycle enzymes (e.g., APX, monodehydroascorbate reductase, dehydroascorbate reducatase and glutathione reductase) and lower levels of malondialdehyde content. Conclusions These results suggest that the expression of native cytosolic SOD and APX simultaneously activated the antioxidative defense mechanisms via cyclic ROS scavenging, thereby improving its tolerance to cold stress. PMID:25091029

Increased expression of native cytosolic Cu/Zn superoxide dismutase and ascorbate peroxidase improves tolerance to oxidative and chilling stresses in cassava (Manihot esculenta Crantz).

PubMed

Xu, Jia; Yang, Jun; Duan, Xiaoguang; Jiang, Yueming; Zhang, Peng

2014-08-05

Cassava (Manihot esculenta Crantz) is a tropical root crop, and is therefore, extremely sensitive to low temperature; its antioxidative response is pivotal for its survival under stress. Timely turnover of reactive oxygen species (ROS) in plant cells generated by chilling-induced oxidative damages, and scavenging can be achieved by non-enzymatic and enzymatic reactions in order to maintain ROS homeostasis. Transgenic cassava plants that co-express cytosolic superoxide dismutase (SOD), MeCu/ZnSOD, and ascorbate peroxidase (APX), MeAPX2, were produced and tested for tolerance against oxidative and chilling stresses. The up-regulation of MeCu/ZnSOD and MeAPX2 expression was confirmed by the quantitative reverse transcriptase-polymerase chain reaction, and enzymatic activity analyses in the leaves of transgenic cassava plant lines with a single-transgene integration site. Upon exposure to ROS-generating agents, 100 μM ROS-generating reagent methyl viologen and 0.5 M H₂O₂, higher levels of enzymatic activities of SOD and APX were detected in transgenic plants than the wild type. Consequently, the oxidative stress parameters, such as lipid peroxidation, chlorophyll degradation and H₂O₂ synthesis, were lower in the transgenic lines than the wild type. Tolerance to chilling stress at 4°C for 2 d was greater in transgenic cassava, as observed by the higher levels of SOD, catalase, and ascorbate-glutathione cycle enzymes (e.g., APX, monodehydroascorbate reductase, dehydroascorbate reducatase and glutathione reductase) and lower levels of malondialdehyde content. These results suggest that the expression of native cytosolic SOD and APX simultaneously activated the antioxidative defense mechanisms via cyclic ROS scavenging, thereby improving its tolerance to cold stress.

The Cu-Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Secondo, Agnese; De Mizio, Mariarosaria; Zirpoli, Laura

The Cu-Zn superoxide dismutase (SOD1) belongs to a family of isoenzymes that are able to dismutate the oxygen superoxide in hydrogen peroxide and molecular oxygen. This enzyme is secreted by many cellular lines and it is also released trough a calcium-dependent depolarization mechanism involving SNARE protein SNAP 25. Using rat pituitary GH3 cells that express muscarinic receptors we found that SOD1 inhibits P-ERK1/2 pathway trough an interaction with muscarinic M1 receptor. This effect is strengthened by oxotremorine, a muscarinic M agonist and partially reverted by pyrenzepine, an antagonist of M1 receptor; moreover this effect is independent from increased intracellular calciummore » concentration induced by SOD1. Finally, P-ERK1/2 inhibition was accompanied by the reduction of GH3 cell proliferation. These data indicate that SOD1 beside the well studied antioxidant properties can be considered as a neuromodulator able to affect mitogen-activated protein kinase in rat pituitary cells trough a M1 muscarinic receptor.« less

Isoenzymes of superoxide dismutase in nodules of Phaseolus vulgaris L. , Pisum sativum L. , and Vigna unguiculata (L. ) Walp

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becana, M.; Paris, F.J.; Sandalio, L.M.

1989-08-01

The activity and isozymic composition of superoxide dismutase were determined in nodules of Phaseolus vulgaris L., Pisum sativum L., and Vigna unguiculata (L.) Walp. A Mn-SOD was present in Rhizobium and two in Bradyrhizobium and bacteroids. Nodule mitochondria from all three legume species had a single Mn-SOD with similar relative mobility, whereas the cytosol contained several CuZn-SODs: two in Phaseolus and Pisum, and four in Vigna. In the cytoplasm of V. unguiculata nodules, a Fe-containing SOD was also present, with an electrophoretic mobility between those of CuZn- and Mn-SODs, and an estimated molecular weight of 57,000. Total SOD activity ofmore » the soluble fraction of host cells, expressed on a nodule fresh weight basis, exceeded markedly that of bacteroids. Likewise, specific SOD activities of free-living bacteria were superior or equal to those of their symbiotic forms. Soluble extracts of bacteria and bacteroids did not show peroxidase activity, but the nodule cell cytoplasm contained diverse peroxidase isozymes which were readily distinguishable from leghemoglobin components by electrophoresis. Data indicated that peroxidases and leghemoglobins did not significantly interfere with SOD localization on gels. Treatment with chloroform-ethanol scarcely affected the isozymic pattern of SODs and peroxidases, and had limited success in the removal of leghemoglobin.« less

A role for Candida albicans superoxide dismutase enzymes in glucose signaling.

PubMed

Broxton, Chynna N; He, Bixi; Bruno, Vincent M; Culotta, Valeria C

2018-01-01

The Saccharomyces cerevisiae and Candida albicans yeasts have evolved to differentially use glucose for fermentation versus respiration. S. cerevisiae is Crabtree positive, where glucose represses respiration and promotes fermentation, while the opportunistic fungal pathogen C. albicans is Crabtree negative and does not repress respiration with glucose. We have previously shown that glucose control in S. cerevisiae involves the antioxidant enzyme Cu/Zn superoxide dismutase (SOD1), where H 2 O 2 generated by SOD1 stabilizes the casein kinase YCK1 for glucose sensing. We now demonstrate that C. albicans SODs also participate in glucose regulation. C. albicans expresses two cytosolic SODs, Cu/Zn SOD1 and Mn containing SOD3, and both complemented a S. cerevisiae sod1Δ mutant in stabilizing YCK1. Moreover, in C. albicans cells, both SODs functioned to repress glucose transporter genes in response to glucose. However, the action of SODs in glucose control has diverged in the two yeasts. In S. cerevisiae, SOD1 specifically functions in the glucose sensing pathway involving YCK1 and the RGT1 repressor, but the analogous YCK/RGT1 pathway in C. albicans shows no control by SOD enzymes. Instead C. albicans SODs work in the glucose repression pathway involving the MIG1 transcriptional repressor. In C. albicans, the SODs repress glucose uptake, while in S. cerevisiae, SOD1 activates glucose uptake, in accordance with the divergent modes for glucose utilization in these two distantly related yeasts. Copyright © 2017 Elsevier Inc. All rights reserved.

The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma.

PubMed

Topic, Aleksandra; Francuski, Djordje; Nikolic, Aleksandra; Milosevic, Katarina; Jovicic, Snezana; Markovic, Bojan; Djukic, Mirjana; Radojkovic, Dragica

2017-08-01

The significance of oxidative stress in pathogenesis of childhood asthma was recognized, but its role in the clinical manifestations of disease is still unclear. The study was conducted in 96 asthmatic children. The urinary biomarker of oxidative stress, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG/creatinine) was determined by using HPLC-MS/MS. ELISA was performed to measure myeloperoxidase (MPO) and Cu,Zn- superoxide dismutase (Cu,Zn-SOD) in serum. Logistic regression analysis revealed that female gender, tobacco smoke exposure, and increased 8-oxodG/creatinine were associated with risk for intermittent asthma, while the positive allergy test and increased Cu,Zn-SOD were associated with eczema in asthmatic children. Higher MPO (p = 0.033), and percent of granulocytes (p = 0.030) were found in severe persistent asthma in comparison to intermittent or mild persistent asthma. The main findings that TSE-induced oxidative stress is a risk for intermittent asthma and eczema may be clinically significant for the disease prevention and therapeutic improvements.

Activation of immunity, immune response, antioxidant ability, and resistance against Vibrio alginolyticus in white shrimp Litopenaeus vannamei decrease under long-term culture at low pH.

PubMed

Chen, Yu-Yuan; Chen, Jiann-Chu; Tseng, Kuei-Chi; Lin, Yong-Chin; Huang, Chien-Lun

2015-10-01

The growth, activation of immunity, immune parameters, and transcript levels of cytMnSOD, mtMnSOD, ecCuZnSOD, glutathione peroxidase (GPx), catalase, lysozyme, and penaeidin 3a were examined in white shrimp Litopenaeus vannamei reared at pH 6.8 and 8.1 after 24 weeks. No significant difference in growth was observed between the two groups. An in vitro study indicated that phenoloxidase activity and respiratory bursts (RB, release of the superoxide anion) were significantly higher in the haemocytes of pH 8.1 shrimp (shrimp reared at pH 8.1) than in pH 6.8 shrimp (shrimp reared at pH 6.8). An in vivo study indicated that the levels of immune parameters of pH 8.1 shrimp were significantly higher than in pH 6.8 shrimp, and the transcript levels of cytMnSOD, ecCuZnSOD, glutathione peroxidase, lysozyme, and penaeidin 3a were down-regulated in pH 6.8 shrimp. In another experiment, shrimp reared at pH 6.8 and 8.1 for 24 weeks were challenged with Vibrio alginolyticus. The mortality rate of pH 6.8 shrimp was significantly higher than in pH 8.1 shrimp over 12-168 h. Phagocytic activity, phagocytic index, and clearance efficiency to V. alginolyticus were significantly lower in pH 6.8 shrimp. We concluded that shrimp under long-term culture at pH 6.8 exhibited decreased resistance against V. alginolyticus as evidenced by reductions in the activation of immunity and immune parameters together with decreased transcript levels of cytMnSOD, ecCuZnSOD, GPx, lysozyme, and penaeidin 3a. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment with Parkinsonia aculeata combats insulin resistance-induced oxidative stress through the increase in PPARγ/CuZn-SOD axis expression in diet-induced obesity mice.

PubMed

Araújo, Tiago Gomes; Oliveira, Alexandre Gabarra; Vecina, Juliana Falcato; Marin, Rodrigo Miguel; Franco, Eryvelton Souza; Abdalla Saad, Mario J; de Sousa Maia, Maria Bernadete

2016-08-01

Parkinsonia aculeata L. (Caesalpiniaceae) is a traditional ethnomedicine and has been used for the empiric treatment of hyperglycemia, without scientific background. Mechanistic analyses at molecular level from the antioxidant mechanism observed by P. aculeata are required. Herein the effects of the treatment by hydroethanolic extract partitioned with ethyl acetate of P. aculeata aerial parts (HEPa/EtOAc) in mice fed a high-fat diet that share many obesity phenotypes with humans were evaluated. The animals were treated orally with HEPa/EtOAc (125 and 250 mg/kg/day) and pioglitazone (5 mg/kg/day), for 16 days. After the treatment, HEPa/EtOAc reduced fasting serum glucose and insulin levels, as well as homeostasis model assessment for insulin resistance. In addition, an improvement in glucose intolerance was also observed. Indeed, a reduction in the circulating levels of TNF-α and IL-6 was also observed. Furthermore, at molecular level, it was demonstrated that the HEPa/EtOAc treatment was able to improve these physiological parameters, through the activation of peroxisome proliferator-activated receptor γ (PPARγ) per si, as well as the enhancement of antioxidant mechanism by an increase in PPARγ/Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD) axis expression in liver and adipose tissue. In sum, P. aculeata is effective to improve insulin resistance in a mouse model of obesity and this effect seems to involve the antioxidant and anti-inflammatory mechanisms through the increase in PPARγ/CuZn-SOD axis expression.

Salivary Antigen-5/CAP Family Members Are Cu2+-dependent Antioxidant Enzymes That Scavenge O2⨪ and Inhibit Collagen-induced Platelet Aggregation and Neutrophil Oxidative Burst*

PubMed Central

Assumpção, Teresa C. F.; Ma, Dongying; Schwarz, Alexandra; Reiter, Karine; Santana, Jaime M.; Andersen, John F.; Ribeiro, José M. C.; Nardone, Glenn; Yu, Lee L.; Francischetti, Ivo M. B.

2013-01-01

The function of the antigen-5/CAP family of proteins found in the salivary gland of bloodsucking animals has remained elusive for decades. Antigen-5 members from the hematophagous insects Dipetalogaster maxima (DMAV) and Triatoma infestans (TIAV) were expressed and discovered to attenuate platelet aggregation, ATP secretion, and thromboxane A2 generation by low doses of collagen (<1 μg/ml) but no other agonists. DMAV did not interact with collagen, glycoprotein VI, or integrin α2β1. This inhibitory profile resembles the effects of antioxidants Cu,Zn-superoxide dismutase (Cu,Zn-SOD) in platelet function. Accordingly, DMAV was found to inhibit cytochrome c reduction by O2⨪ generated by the xanthine/xanthine oxidase, implying that it exhibits antioxidant activity. Moreover, our results demonstrate that DMAV blunts the luminescence signal of O2⨪ generated by phorbol 12-myristate 13-acetate-stimulated neutrophils. Mechanistically, inductively coupled plasma mass spectrometry and fluorescence spectroscopy revealed that DMAV, like Cu,Zn-SOD, interacts with Cu2+, which provides redox potential for catalytic removal of O2⨪. Notably, surface plasmon resonance experiments (BIAcore) determined that DMAV binds sulfated glycosaminoglycans (e.g. heparin, KD ∼100 nmol/liter), as reported for extracellular SOD. Finally, fractions of the salivary gland of D. maxima with native DMAV contain Cu2+ and display metal-dependent antioxidant properties. Antigen-5/CAP emerges as novel family of Cu2+-dependent antioxidant enzymes that inhibit neutrophil oxidative burst and negatively modulate platelet aggregation by a unique salivary mechanism. PMID:23564450

Reactive oxygen species on bone mineral density and mechanics in Cu,Zn superoxide dismutase (Sod1) knockout mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smietana, Michael J.; Arruda, Ellen M.; Mechanical Engineering, University of Michigan, 2250 GG Brown, 2350 Hayward, Ann Arbor, MI 48109

Research highlights: {yields} Reactive oxygen species (ROS) are considered to be a factor in the onset of a number of age-associated conditions, including loss of BMD. {yields} Cu,Zn-superoxide dismutase (Sod1) deficient mice have increased ROS, reduced bone mineral density, decreased bending stiffness, and decreased strength compared to WT controls. {yields} Increased ROS caused by the deficiency of Sod1, may be responsible for the changes in BMD and bone mechanics and therefore represent an appropriate model for studying mechanisms of age-associated bone loss. -- Abstract: Reactive oxygen species (ROS) play a role in a number of degenerative conditions including osteoporosis. Micemore » deficient in Cu,Zn-superoxide dismutase (Sod1) (Sod1{sup -/-} mice) have elevated oxidative stress and decreased muscle mass and strength compared to wild-type mice (WT) and appear to have an accelerated muscular aging phenotype. Thus, Sod1{sup -/-} mice may be a good model for evaluating the effects of free radical generation on diseases associated with aging. In this experiment, we tested the hypothesis that the structural integrity of bone as measured by bending stiffness (EI; N/mm{sup 2}) and strength (MPa) is diminished in Sod1{sup -/-} compared to WT mice. Femurs were obtained from male and female WT and Sod1{sup -/-} mice at 8 months of age and three-point bending tests were used to determine bending stiffness and strength. Bones were also analyzed for bone mineral density (BMD; mg/cc) using micro-computed tomography. Femurs were approximately equal in length across all groups, and there were no significant differences in BMD or EI with respect to gender in either genotype. Although male and female mice demonstrated similar properties within each genotype, Sod1{sup -/-} mice exhibited lower BMD and EI of femurs from both males and females compared with gender matched WT mice. Strength of femurs was also lower in Sod1{sup -/-} mice compared to WT as well as between genders. These data indicate that increased oxidative stress, due to the deficiency of Sod1 is associated with decreased bone stiffness and strength and Sod1{sup -/-} mice may represent an appropriate model for studying disease processes in aging bone.« less

ROLE OF COPPER,ZINC-SUPEROXIDE DISMUTASE IN CATALYZING NITROTYROSINE FORMATION IN MURINE LIVER

USDA-ARS?s Scientific Manuscript database

The solely known function of Cu,Zn-superoxide dismutase (SOD1) is to catalyze the dismutation of superoxide anion into hydrogen peroxide. Our objective was to determine if SOD1 catalyzed murine liver protein nitration induced by acetaminophen (APAP) and lipopolysaccharide (LPS). Liver and plasma ...

Zymography Methods to Simultaneously Analyze Superoxide Dismutase and Catalase Activities: Novel Application for Yeast Species Identification.

PubMed

Gamero-Sandemetrio, Esther; Gómez-Pastor, Rocío; Matallana, Emilia

2017-01-01

We provide an optimized protocol for a double staining technique to analyze superoxide dismutase enzymatic isoforms Cu-Zn SOD (Sod1) and Mn-SOD (Sod2) and catalase in the same polyacrylamide gel. The use of NaCN, which specifically inhibits yeast Sod1 isoform, allows the analysis of Sod2 isoform while the use of H 2 O 2 allows the analysis of catalase. The identification of a different zymography profiling of SOD and catalase isoforms in different yeast species allowed us to propose this technique as a novel yeast identification and classification strategy.

Germination, Physiological Responses and Gene Expression of Tall Fescue (Festuca arundinacea Schreb.) Growing under Pb and Cd

PubMed Central

Lou, Yanhong; Zhao, Peng; Wang, Deling; Amombo, Erick; Sun, Xin; Wang, Hui; Zhuge, Yuping

2017-01-01

Cadmium (Cd) and lead (Pb) are recognized as the most toxic metal ions due to their detrimental effects not only to plants, but also to humans. The objective of this study was to investigate the effects of Cd and Pb treatments on seed germination, plant growth, and physiological response in tall fescue (Festuca arundinacea Schreb.). We employed six treatments: CK (nutrient solution as control), T1 (1000 mg L-1 Pb), T2 (50 mg L-1 Cd), T3 (150 mg L-1 Cd), T4 (1000 mg L-1 Pb+50 mg L-1 Cd), T5 (1000 mg L-1 Pb+150 mg L-1 Cd). Antagonistic and synergistic actions were observed in tall fescue under Pb and Cd combined treatments. Under low Cd, plants exhibited higher relative germination rate, germ length, VSGR, catalase (CAT) and peroxidase (POD) activities. Additionally, in the shoots, the gene expression level of Cu/Zn SOD, FeSOD, POD, GPX, translocation factors, MDA, EL, and soluble protein contents were reduced under Pb stress. Conversely, under high Cd level, there was a decline in NRT, Pb content in shoots, Pb translocation factors, CAT activity; and an increase in VSGR, Pb content in roots, gene expression level of Cu/ZnSOD and POD in tall fescue exposed to Pb2+ regimes. On the other hand, tall fescue plants treated with low Cd exhibited lower relative germination rate, germination index, germ length, NRT, Cd content in roots. On the other hand there was higher Cd content, Cd translocation factor, CAT and POD activities, and gene expression level of Cu/Zn SOD, FeSOD, POD, GPX under Pb treatment compared with single Cd2+ treatment in the shoots. However, after high Cd exposure, plants displayed lower NRT, Cd content, CAT activity, and exhibited higher Cd contents, Cd translocation factor, MDA content, gene expression level of Cu/ZnSOD and GPX with the presence of Pb2+ relative to single Cd2+ treatment. These findings lead to a conclusion that the presence of low Cd level impacted positively towards tall fescue growth under Pb stress, while high level of Cd impacted negatively. In summary, antioxidant enzymes responded to Cd and Pb interaction at an early stage of exposure, and their gene expression profiles provided more details of the activation of those systems. PMID:28046098

Germination, Physiological Responses and Gene Expression of Tall Fescue (Festuca arundinacea Schreb.) Growing under Pb and Cd.

PubMed

Lou, Yanhong; Zhao, Peng; Wang, Deling; Amombo, Erick; Sun, Xin; Wang, Hui; Zhuge, Yuping

2017-01-01

Cadmium (Cd) and lead (Pb) are recognized as the most toxic metal ions due to their detrimental effects not only to plants, but also to humans. The objective of this study was to investigate the effects of Cd and Pb treatments on seed germination, plant growth, and physiological response in tall fescue (Festuca arundinacea Schreb.). We employed six treatments: CK (nutrient solution as control), T1 (1000 mg L-1 Pb), T2 (50 mg L-1 Cd), T3 (150 mg L-1 Cd), T4 (1000 mg L-1 Pb+50 mg L-1 Cd), T5 (1000 mg L-1 Pb+150 mg L-1 Cd). Antagonistic and synergistic actions were observed in tall fescue under Pb and Cd combined treatments. Under low Cd, plants exhibited higher relative germination rate, germ length, VSGR, catalase (CAT) and peroxidase (POD) activities. Additionally, in the shoots, the gene expression level of Cu/Zn SOD, FeSOD, POD, GPX, translocation factors, MDA, EL, and soluble protein contents were reduced under Pb stress. Conversely, under high Cd level, there was a decline in NRT, Pb content in shoots, Pb translocation factors, CAT activity; and an increase in VSGR, Pb content in roots, gene expression level of Cu/ZnSOD and POD in tall fescue exposed to Pb2+ regimes. On the other hand, tall fescue plants treated with low Cd exhibited lower relative germination rate, germination index, germ length, NRT, Cd content in roots. On the other hand there was higher Cd content, Cd translocation factor, CAT and POD activities, and gene expression level of Cu/Zn SOD, FeSOD, POD, GPX under Pb treatment compared with single Cd2+ treatment in the shoots. However, after high Cd exposure, plants displayed lower NRT, Cd content, CAT activity, and exhibited higher Cd contents, Cd translocation factor, MDA content, gene expression level of Cu/ZnSOD and GPX with the presence of Pb2+ relative to single Cd2+ treatment. These findings lead to a conclusion that the presence of low Cd level impacted positively towards tall fescue growth under Pb stress, while high level of Cd impacted negatively. In summary, antioxidant enzymes responded to Cd and Pb interaction at an early stage of exposure, and their gene expression profiles provided more details of the activation of those systems.

Optimization of dietary zinc for egg production and antioxidant capacity in Chinese egg-laying ducks fed a diet based on corn-wheat bran and soybean meal.

PubMed

Chen, W; Wang, S; Zhang, H X; Ruan, D; Xia, W G; Cui, Y Y; Zheng, C T; Lin, Y C

2017-07-01

The aim of this study was to evaluate the effect of zinc supplementation on productive performance and antioxidant status in laying ducks. Five-hundred-four laying ducks were divided into 7 treatments, each containing 6 replicates of 12 ducks. The ducks were caged individually and fed a corn-soybean meal and wheat bran basal diet (37 mg Zn/kg) or the basal diet supplemented with 15, 30, 45, 60, 75, or 90 mg Zn/kg (as zinc sulfate). During the early laying period of 10 d (daily egg production <80%), egg production, daily egg mass, and FCR increased quadratically with increasing dietary Zn levels (P < 0.05). The highest egg production and daily egg weight were obtained when 30 or 45 mg Zn/kg diet was supplemented, with lowest FCR. Similarly, the highest egg production and daily egg mass were observed in the group supplemented with 30 or 45 mg Zn/kg during the peak laying period of the subsequent 120 d (daily egg production >80%). Average egg weight and feed intake did not differ among the groups of graded Zn supplementation.The egg quality was not affected by dietary Zn, including the egg shape index, Haugh unit, yolk color score, egg composition, and shell thickness. The activities of plasma activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) increased in a quadratic manner (P < 0.001) with increasing supplemental Zn. Plasma concentration of Zn increased quadratically (P < 0.05) as dietary Zn increased. The hepatic activity of Cu/Zn-SOD and GSH-PX increased quadratically (P < 0.05) with increasing dietary Zn. Plasma Zn concentrations were positively correlated with activities of T-SOD (P < 0.05), and positively with plasma Cu. Plasma concentration of reduced glutathione was correlated with plasma Cu. In conclusion, supplementation of Zn at 30 or 45 mg/kg to a corn-wheat bran and soybean basal diet may improve the productive performance and enhance the antioxidant capacity. © 2017 Poultry Science Association Inc.

Rosette iron deficiency transcript and microRNA profiling reveals links between copper and iron homeostasis in Arabidopsis thaliana

PubMed Central

Waters, Brian M.; Stein, Ricardo J.

2012-01-01

Iron (Fe) is an essential plant micronutrient, and its deficiency limits plant growth and development on alkaline soils. Under Fe deficiency, plant responses include up-regulation of genes involved in Fe uptake from the soil. However, little is known about shoot responses to Fe deficiency. Using microarrays to probe gene expression in Kas-1 and Tsu-1 ecotypes of Arabidopsis thaliana, and comparison with existing Col-0 data, revealed conserved rosette gene expression responses to Fe deficiency. Fe-regulated genes included known metal homeostasis-related genes, and a number of genes of unknown function. Several genes responded to Fe deficiency in both roots and rosettes. Fe deficiency led to up-regulation of Cu,Zn superoxide dismutase (SOD) genes CSD1 and CSD2, and down-regulation of FeSOD genes FSD1 and FSD2. Eight microRNAs were found to respond to Fe deficiency. Three of these (miR397a, miR398a, and miR398b/c) are known to regulate transcripts of Cu-containing proteins, and were down-regulated by Fe deficiency, suggesting that they could be involved in plant adaptation to Fe limitation. Indeed, Fe deficiency led to accumulation of Cu in rosettes, prior to any detectable decrease in Fe concentration. ccs1 mutants that lack functional Cu,ZnSOD proteins were prone to greater oxidative stress under Fe deficiency, indicating that increased Cu concentration under Fe limitation has an important role in oxidative stress prevention. The present results show that Cu accumulation, microRNA regulation, and associated differential expression of Fe and CuSOD genes are coordinated responses to Fe limitation. PMID:22962679

[The influence of nitrates on platelet oxygen metabolism: in vitro studies].

PubMed

Buczyński, A; Dziedziczak-Buczyńska, M; Gnitecki, W; Kocur, J

1999-01-01

Our investigations were carried out on human blood platelets obtained from persons aged 20-23, free from any systemic diseases. Drugs were incubated with blood platelets. Changes of antioxidant enzymes were detected. Glyceryl trinitrate increased the activity of Zn Cu-SOD (4.62%) and GPx (275.91%), concentration of ATP (13.01%) and the blood platelets aggregations (17.88%). Izosorbide dinitrate increased the activity of ZnCu-SOD (19.46%), GPx (150.36%) and Cat (15.62%), increased concentration of ATP (23.73%) and blood platelets aggregation (3.64%). Both preparats decreased concentration of MDA (Sustonit--30.79%, Iso-Mack--35.04%). Gliceryl trinitrate decreased the activity of catalase otherwise izosorbide dinitrate increased the activity of this enzyme.

Biochemical analysis of reactive oxygen species production and antioxidative responses in unripe avocado (Persea americana Mill var Hass) fruits in response to wounding.

PubMed

Castro-Mercado, E; Martinez-Diaz, Y; Roman-Tehandon, N; Garcia-Pineda, E

2009-03-01

We analyzed the production of reactive oxygen species (ROS) and of detoxifying enzymes and enzymes of the ascorbate (ASC) acid cycle in avocado fruit (Pesea Americana Mill cv Hass) in response to wounding. The levels of superoxide anion (O(2-), hydroxyl radicals (OH.) and hydrogen peroxide (H(2)O(2)) increased at 15 min and 2 and 15 h post-wounding. Peroxidase (POD) activity had increased to high levels 24 h after wounding; in contrast, catalase and superoxide dismutase (SOD) levels hat decreased significantly at 24 h post-treatment. Basic POD was the major POD form induced, and the levels of at least three apoplastic POD isozymes -increased following wounding. Using specific inhibitors, we characterized one MnSOD and two CuZnSOD isozymes. CuZnSOD activities decreased notably 12 h after treatment. The activities of dehydroascorbate reductase and glutathione reductase increased dramatically following the wounding treatment, possibly as a means to compensate for the redox changes due to ROS production.

Polarizable molecular mechanics studies of Cu(I)/Zn(II) superoxide dismutase: bimetallic binding site and structured waters.

PubMed

Gresh, Nohad; El Hage, Krystel; Perahia, David; Piquemal, Jean-Philip; Berthomieu, Catherine; Berthomieu, Dorothée

2014-11-05

The existence of a network of structured waters in the vicinity of the bimetallic site of Cu/Zn-superoxide dismutase (SOD) has been inferred from high-resolution X-ray crystallography. Long-duration molecular dynamics (MD) simulations could enable to quantify the lifetimes and possible interchanges of these waters between themselves as well as with a ligand diffusing toward the bimetallic site. The presence of several charged or polar ligands makes it necessary to resort to second-generation polarizable potentials. As a first step toward such simulations, we benchmark in this article the accuracy of one such potential, sum of interactions between fragments Ab initio computed (SIBFA), by comparisons with quantum mechanics (QM) computations. We first consider the bimetallic binding site of a Cu/Zn-SOD, in which three histidines and a water molecule are bound to Cu(I) and three histidines and one aspartate are bound to Zn(II). The comparisons are made for different His6 complexes with either one or both cations, and either with or without Asp and water. The total net charges vary from zero to three. We subsequently perform preliminary short-duration MD simulations of 296 waters solvating Cu/Zn-SOD. Six representative geometries are selected and energy-minimized. Single-point SIBFA and QM computations are then performed in parallel on model binding sites extracted from these six structures, each of which totals 301 atoms including the closest 28 waters from the Cu metal site. The ranking of their relative stabilities as given by SIBFA is identical to the QM one, and the relative energy differences by both approaches are fully consistent. In addition, the lowest-energy structure, from SIBFA and QM, has a close overlap with the crystallographic one. The SIBFA calculations enable to quantify the impact of polarization and charge transfer in the ranking of the six structures. Five structural waters, which connect Arg141 and Glu131, are endowed with very high dipole moments (2.7-3.0 Debye), equal and larger than the one computed by SIBFA in ice-like arrangements (2.7 D). Copyright © 2014 Wiley Periodicals, Inc.

Decreased Nephrin and GLEPP-1, But Increased VEGF, Flt-1, and Nitrotyrosine, Expressions in Kidney Tissue Sections From Women With Preeclampsia

PubMed Central

Zhao, Shuang; Gu, Xin; Groome, Lynn J.; Wang, Yuping

2011-01-01

Renal injury is a common pathophysiological feature in women with preeclampsia as evidenced by increased protein leakage (proteinuria) and glomerular injury (glomerular endotheliosis). Recently, podocyturia was found in preeclampsia, suggesting podocyte shedding occurs in this pregnancy disorder. However, podocyte function in preeclampsia is poorly understood. In this study, the authors have examined podocyte-specific protein expressions for nephrin, glomerular epithelial protein 1 (GLEPP-1), and ezrin in kidney biopsy tissue sections from women with preeclampsia. Expressions for vascular endothelial growth factor (VEGF) and its receptor Flt-1 and oxidative stress marker nitrotyrosine and antioxidant CuZn-superoxide dismutase (CuZn-SOD) were also examined. Kidney tissue sections from nonhypertensive and chronic hypertensive participants were stained as controls. The findings were (1) nephrin and GLEPP-1 were mainly expressed in glomerular podocytes; (2) ezrin was expressed in both glomerular podocytes and tubular epithelial cells; (3) compared to tissue sections from nonhypertensive and chronic hypertensive participants, nephrin and GLEPP-1 expressions were much reduced in tissue sections from preeclampsia and ezrin expression was reduced in podocytes; (4) enhanced VEGF, Flt-1, and nitrotyrosine, but reduced CuZn-SOD, expressions were observed in both glomerular podocytes and endothelial cells in tissue sections from preeclampsia; and (5) the expression pattern for nephrin, GLEPP-1, ezrin, VEGF, Flt-1, and CuZn-SOD were similar between tissue sections from nonhypertensive and chronic hypertensive participants. Although the authors could not conclude from this biopsy study whether the podocyte injury is the cause or effect of the preeclampsia phenotype, the data provide compelling evidence that podocyte injury accompanied by altered angiogenesis process and increased oxidative stress occurs in kidney of patients with preeclampsia. PMID:19528353

Effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats.

PubMed

Tang, Rong; Zhou, Qiaoling; Liu, Zhichun; Xiao, Zhou; Pouranan, Veeraragoo

2011-01-01

To explore effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats (SHR) and the mechanisms underlying the protection against renal damage. Fifteen male SHRs (22 weeks old) were randomly divided into 3 groups (n=5 in each group): a SHR group, a fosinopril group [10 mg/(kg.d)], and a losartan group [50 mg/(kg.d)]. Age-matched Wistar-Kyoto (WKY) rats were chosen for a control group. Eight weeks later, tail arterial pressure, 24 hours urinary protein (Upro),urinary N-acetyl-β-D-glucosaminidase (NAGase) were measured. Renal pathological changes were examined under light microscopy by HE staining. The renal mRNA and protein expression of Klotho were determined by RT-PCR, immunohistochemical staining or Western blot. The levels of total antioxidant capacity (TAOC), malondialdehyde (MDA), Cu/Zn superoxide dismutase (Cu/Zn-SOD), Mn superoxide dismutase (Mn-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. The typical pathological characteristics of hypertensive renal damage were observed in the kidney of the SHR group.Compared with the SHR group, the systolic pressure, Upro, and urinary NAGase, the content of MDA and renal pathological damage was reduced while the renal Klotho expression and activities of TAOC, Cu/Zn-SOD, CAT, and GSH-Px were increased (P<0.05 or P<0.01) in the fosinopril or losartan group. There was no significant difference in renal Mn-SOD level among the 4 groups (P>0.05). Fosinopril and losartan can exert protection against hypertensive renal damage through upregulating Klotho expression as well as reducing oxidative stress.

The association of oxidant-antioxidant status in patients with chronic renal failure.

PubMed

Aziz, Manal A; Majeed, Ghanim H; Diab, Kareem S; Al-Tamimi, Raid J

2016-01-01

Oxidative stress has been linked to disease progression, including chronic renal failure (CRF). The aim of the present study was to determine malondialdehyde (MDA) as a sign of lipid peroxidation, and to investigate the association between antioxidant activities and three trace elements, in 49 patients with CRF. The erythrocyte and plasma trace elements [selenium (Se), zinc (Zn), and copper (Cu)] and antioxidant defense levels were determined: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), vitamins E and C. The obtained values were compared with 42 age- and sex-matched healthy controls. There were significantly lower mean values of plasma Se, GPx, vitamins E and C, erythrocyte Se, SOD and CAT levels in the patient group compared to the control group (p < 0.001). Plasma MDA showed a significant increase in all CRF patients in comparison with controls. No significant difference was found in plasma Cu, Zn, and erythrocyte GPx, Cu and Zn levels between patient and control groups. These findings indicate oxidative stress is present in patients of CRF, and may serve to establish a simple protocol for evaluation of renal function.

Properties of purified cytosolic isoenzyme I of Cu,Zn-superoxide dismutase from Nicotiana plumbaginifolia leaves.

PubMed

Ragusa, S; Cambria, M T; Scarpa, M; Di Paolo, M L; Falconi, M; Rigo, A; Cambria, A

2001-11-01

The isoenzyme I of cytosolic Cu,Zn-superoxide dismutase (SOD) from Nicotiana plumbaginifolia (tobacco) leaves has been purified to apparent homogeneity. The relative molecular mass of the native isoenzyme, determined by gel filtration chromatography, is about 33.2 kDa. SDS-polyacrylamide gel electrophoresis shows that the enzyme is composed of two equal subunits of 16.6 kDa The isolectric point, assayed by isoelectric focusing, in the pH range of 3.5-6.5, is 4.3. The enzyme stability was tested at different temperatures, pH, and concentration of inhibitors (KCN and H(2)O(2)). The catalytic constant (k(cat)) was 1.17 +/- 0.14 x 10(9) M(-1) s(-1) at pH 9.9 and 0.1 M ionic strength. The activation energy of the thermal denaturation process is 263 kJ mol(-1). The electrostatic surface potential of the modeled tobacco Cu,Zn-SOD I was calculated showing that the functional spatial network of charges on the protein surface has been maintained, independently of the amino acid substitution around the active sites. Copyright 2001 Academic Press.

E.s.r., magnetic, optical and biological (SOD and antimicrobial) studies of imidazolate bridged Cu II-Zn II and Cu II-Ni II complexes with tris(2-amino ethyl)amine as capping ligand: a plausible model for superoxide dismutase

NASA Astrophysics Data System (ADS)

Singh, Nripendra; Shukla, K. K.; Patel, R. N.; Chauhan, U. K.; Shrivastava, R.

2003-11-01

X-band e.s.r. and optical absorption spectra of the imidazolate bridged heterobimetallic complexes [(tren)Cu-E-Im-Zn-(tren)](ClO 4) 3 and [(tren)Cu-E-Im-Ni-(tren)](ClO 4) 3, where trentris(2-aminoethyl)amine, E-Im=2-ethylimidazolate ion and the related mononuclear complexes [Cu(tren)](ClO 4) 2 and [(tren)Cu-E-ImH)](ClO 4) 2 have been described. Biological activities (superoxide dismutase and antimicrobial) have also been measured and compared with reported complexes.

Effect of Concentrated Apple Extract on Experimental Colitis Induced by Acetic Acid.

PubMed

Pastrelo, Maurício Mercaldi; Dias Ribeiro, Carla Caroline; Duarte, Joselmo Willamys; Bioago Gollücke, Andréa Pitelli; Artigiani-Neto, Ricardo; Ribeiro, Daniel Araki; Miszputen, Sender Jankiel; Fujiyama Oshima, Celina Tizuko; Ribeiro Paiotti, Ana Paula

2017-01-01

Reactive oxygen and nitrogen species (ROS/RNS) play a crucial role in inflammatory bowel disease (IBD) exacerbating the chronic inflammatory process. Endogenous and diet antioxidants can neutralize these compounds. The apple is widely consumed, with several antioxidant activity compounds. The present study evaluated the effects of concentrated apple extract (CAE) in acetic acid induced colitis. 29 Wistar male rats were randomized into 5 groups. G1-Sham/saline solution, G2-CAE/control, G3-acetic acid/control, G4-curative- CAE treatment and G5-preventive-CAE treatment. Eight days later, the animals were euthanized and the colonic segment resected for macroscopic and histological analysis. Gene expression was evaluated for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), catalase and copper and zinc superoxide dismutase (CuZnSOD) by quantitative real time PCR, while protein expression was assessed for iNOS, COX-2 and 8-hydroxy-20-deoxyguanosine (8-OHdG) via immunohistochemistry. The groups G3, G4 and G5 had weight loss, while G5 had weight increase at the end of the experiment. The treatment with CAE reduced the macroscopic and microscopic injury, decreased iNOS mRNA expression and increased CuZnSOD mRNA expression in animals with induced acetic acid-colitis. The findings of the present study suggest that CAE treatment exerts an antioxidant role by downregulating iNOS and upregulating CuZnSOD.

Sperm antioxidant defences decrease during epididymal transit from caput to cauda in parallel with increases in epididymal fluid in the goat (Capra hircus).

PubMed

Rana, Mashidur; Roy, Sudhir C; Divyashree, Bannur C

2017-09-01

The status of antioxidant defences of both spermatozoa and their associated fluids during epididymal transit from the caput to cauda have not been studied so far in any species. Herein we report for the first time that sperm antioxidant defences, namely Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and catalase activity, decrease significantly (P<0.05) from the caput to cauda during epididymal transit in parallel with increases in Cu,Zn-SOD, total SOD and total glutathione peroxidase (GPx) activity in the luminal fluid of the respective segments. However, levels of GPX1 and GPX3 in epididymal fluid did not change significantly from the caput to cauda. Catalase was detected for the first time in goat spermatozoa. A significantly higher total antioxidant capacity of caudal fluid than of the caput suggests a requirement for a rich antioxidant environment for the storage of spermatozoa. The retention of cytoplasmic droplets in most of the caudal spermatozoa confirmed that these droplets do not contribute to the increased antioxidant defences of cauda epididymidal fluid. Thus, the antioxidant defences of the spermatozoa and their associated epididymal fluid are modulated from the caput to cauda in a region-specific manner. This may be one of the compensatory mechanisms of epididymal fluid to scavenge any excess reactive oxygen species produced in the microenvironment of spermatozoa.

Folding of Cu/Zn superoxide dismutase suggests structural hotspots for gain of neurotoxic function in ALS: Parallels to precursors in amyloid disease

PubMed Central

Nordlund, Anna; Oliveberg, Mikael

2006-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease linked to misfolding of the ubiquitous enzyme Cu/Zn superoxide dismutase (SOD). In contrast to other protein-misfolding disorders with similar neuropathogenesis, ALS is not always associated with the in vivo deposition of protein aggregates. Thus, under the assumption that all protein-misfolding disorders share at primary level a similar disease mechanism, ALS constitutes an interesting disease model for identifying the yet-mysterious precursor states from which the cytotoxic pathway emerges. In this study, we have mapped out the conformational repertoire of the apoSOD monomer through analysis of its folding behavior. The results allow us to target the regions of the SOD structure that are most susceptible to unfolding locally under physiological conditions, leading to the exposure of structurally promiscuous interfaces that are normally hidden in the protein’s interior. The structure of this putative ALS precursor is strikingly similar to those implicated in amyloid disease. PMID:16798882

Intravenous superoxide dismutase as a protective agent to prevent impairment of lung function induced by high tidal volume ventilation.

PubMed

Wu, Nan-Chun; Liao, Fan-Ting; Cheng, Hao-Min; Sung, Shih-Hsien; Yang, Yu-Chun; Wang, Jiun-Jr

2017-07-26

Positive-pressure mechanical ventilation is essential in assisting patients with respiratory failure in the intensive care unit and facilitating oxygenation in the operating room. However, it was also recognized as a primary factor leading to hospital-acquired pulmonary dysfunction, in which pulmonary oxidative stress and lung inflammation had been known to play important roles. Cu/Zn superoxide dismutase (SOD) is an important antioxidant, and possesses anti-inflammatory capacity. In this study, we aimed to study the efficacy of Cu/Zn SOD, administered intravenously during high tidal volume (HTV) ventilation, to prevent impairment of lung function. Thirty-eight male Sprague-Dawley rats were divided into 3 groups: 5 h ventilation with (A) low tidal volume (LTV; 8 mL/kg; n = 10), (B) high tidal volume (HTV; 18 mL/kg; n = 14), or (C) HTV and intravenous treatment of Cu/Zn SOD at a dose of 1000 U/kg/h (HTV + SOD; n = 14). Lung function was evaluated both at baseline and after 5-h ventilation. Lung injury was assessed by histological examination, lung water and protein contents in the bronchoalveolar lavage fluid (BALF). Pulmonary oxidative stress was examined by concentrations of methylguanidine (MG) and malondialdehyde (MDA) in BALF, and antioxidative activity by protein expression of glutathione peroxidase-1 (GPx-1) in the lung. Severity of lung inflammation was evaluated by white blood cell and differential count in BALF, and protein expression of inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and mRNA expression of nuclear factor-κB (NF-κB) in the lung. We also examined protein expression of surfactant protein (SP)-A and D and we measured hourly changes in serum nitric oxide (NO) level. Five hours of LTV ventilation did not induce a major change in lung function, whereas 5 h of HTV ventilation induced apparent combined restrictive and obstructive lung disorder, together with increased pulmonary oxidative stress, decreased anti-oxidative activity and increased lung inflammation (P < 0.05). HTV ventilation also decreased SP-A and SP-D expression and suppressed serum NO level during the time course of ventilation. Cu/Zn SOD administered intravenously during HTV ventilation effectively reversed associated pulmonary oxidative stress and lung inflammation (P < 0.05); moreover, it preserved SP-A and SP-D expressions in the lung and increased serum nitric oxide (NO) level, enhancing vascular NO bioavailability. HTV ventilation can induce combined restrictive and obstructive lung disorders. Intravenous administration of Cu/Zn SOD during HTV ventilation can prevent lung function impairment and lung injury via reducing pulmonary oxidative stress and lung inflammation, preserving pulmonary surfactant expression, and enhancing vascular NO bioavailability.

Comparative Analyses of Cu-Zn Superoxide Dismutase (SOD1) and Thioredoxin Reductase (TrxR) at the mRNA Level between Apis mellifera L. and Apis cerana F. (Hymenoptera: Apidae) Under Stress Conditions.

PubMed

Koo, Hyun-Na; Lee, Soon-Gyu; Yun, Seung-Hwan; Kim, Hyun Kyung; Choi, Yong Soo; Kim, Gil-Hah

2016-01-01

This study compared stress-induced expression of Cu-Zn superoxide dismutase (SOD1) and thioredoxin reductase (TrxR) genes in the European honeybee Apis mellifera L. and Asian honeybee Apis cerana F. Expression of both SOD1 and TrxR rapidly increased up to 5 h after exposure to cold (4 °C) or heat (37 °C) treatment and then gradually decreased, with a stronger effect induced by cold stress in A. mellifera compared with A. cerana. Injection of stress-inducing substances (methyl viologen, [MV] and H2O2) also increased SOD1 and TrxR expression in both A. mellifera and A. cerana, and this effect was more pronounced with MV than H2O2. Additionally, we heterologously expressed the A. mellifera and A. cerana SOD1 and TrxR proteins in an Escherichia coli expression system, and detection by SDS-PAGE, confirmed by Western blotting using anti-His tag antibodies, revealed bands at 16 and 60 kDa, respectively. Our results show that the expression patterns of SOD1 and TrxR differ between A. mellifera and A. cerana under conditions of low or high temperature as well as oxidative stress. © The Author 2016. Published by Oxford University Press on behalf of the Entomological Society of America.

Treadmill exercise prevents diabetes-induced increases in lipid peroxidation and decreases in Cu,Zn-superoxide dismutase levels in the hippocampus of Zucker diabetic fatty rats.

PubMed

Kim, Jong Whi; Chae, Junghyun; Nam, Sung Min; Kim, Yo Na; Yoo, Dae Young; Choi, Jung Hoon; Jung, Hyo Young; Song, Wook; Hwang, In Koo; Seong, Je Kyung; Yoon, Yeo Sung

2015-01-01

In the present study, we investigated the effects of treadmill exercise on lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) levels in the hippocampus of Zucker diabetic fatty (ZDF) rats and lean control rats (ZLC) during the onset of diabetes. At 7 weeks of age, ZLC and ZDF rats were either placed on a stationary treadmill or made to run for 1 h/day for 5 consecutive days at 16~22 m/min for 5 weeks. At 12 weeks of age, the ZDF rats had significantly higher blood glucose levels and body weight than the ZLC rats. In addition, malondialdehyde (MDA) levels in the hippocampus of the ZDF rats were significantly higher than those of the ZLC rats whereas SOD1 levels in the hippocampus of the ZDF rats were moderately decreased. Notably, treadmill exercise prevented the increase of blood glucose levels in ZDF rats. In addition, treadmill exercise significantly ameliorated changes in MDA and SOD1 levels in the hippocampus although SOD activity was not altered. These findings suggest that diabetes increases lipid peroxidation and decreases SOD1 levels, and treadmill exercise can mitigate diabetes-induced oxidative damage in the hippocampus.

The expression of superoxide dismutase in Mytilus coruscus under various stressors.

PubMed

Wu, Jiong; Bao, Miaomiao; Ge, Delong; Huo, Liping; Lv, Zhenming; Chi, Changfeng; Liao, Zhi; Liu, Huihui

2017-11-01

Superoxide dismutases (SODs), a by-product of antioxidative defence system, protects organisms for eliminating excess reactive oxygen species (ROS) and maintaining the redox balance of immune system. The complete open reading frames (ORFs) of Cu/Zn-SOD and Mn-SOD were identified from Mytilus coruscus (designated as McSOD and MnSOD) by homologous cloning. The sequence lengths were 474bp and 687bp, encoding 157 and 228 amino acids respectively. The deduced amino acid sequences of McSOD and MnSOD shared high identities with Cu/Zn-SOD and Mn-SOD from other mollusca. The distributions of McSOD and MnSOD were detected in six tissues including adductor, hemocyte, gill, gonad, mantle and hepatopancreas, and the highest expressions were both in gills. The temporal expression of McSOD and MnSOD were up-regulated in gills under a variety of stress factors, including Vibrio parahemolyticus, Aeromonas hydrophila, Cu 2+ and Pb 2+ . After being challenged with V. Parahemolyticus, the expressions of McSOD and MnSOD were increased rapidly at the initial hours, reaching the peaks of 4.9-fold and 15.3-fold respectively, and got to the highest levels of 43.5-fold and 7.1-fold after being challenged with A. hydrophila. The highest point of McSOD mRNA appeared at 15 d after being exposed to copper (7-fold at 0.5 mg/L and 13.2-fold at 1.5 mg/L), except for 0.1 mg/L group of Cu 2+ maintaining to the normal level, but plumbum at 1 d (2.4-fold at 1.0 mg/L and 4.4-fold at 3.0 mg/L) and at 15 d (2.1-fold at 0.2 mg/L). The temporal expression peaks of MnSOD appeared differently after exposing to copper of various concentrations (0.1 mg/L at 10 d with 4.7-fold, 0.5 mg/L at 1 d with 17.9-fold and 1.5 mg/L at 3 d with 13.2-fold). Whereas in plumbum exposing treatments, the 3.0 mg/L group jumped to the peak at 1 d (18.2-fold), the 0.2 mg/L and 1.0 mg/L groups had little change and maintained at the normal level throughout the experiment. The results provided several new evidences for further understanding of the regulatory mechanism of SOD on the innate immune system in bivalve. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations.

PubMed

Lange, Dale J; Shahbazi, Mona; Silani, Vincenzo; Ludolph, Albert C; Weishaupt, Jochen H; Ajroud-Driss, Senda; Fields, Kara G; Remanan, Rahul; Appel, Stanley H; Morelli, Claudia; Doretti, Alberto; Maderna, Luca; Messina, Stefano; Weiland, Ulrike; Marklund, Stefan L; Andersen, Peter M

2017-06-01

Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models. Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems. A previous phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutations. This study investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in patients carrying SOD1 mutations linked to familial amyotrophic lateral sclerosis (fALS/SOD1). A multicenter (5 sites), open-label, 9-month-duration, dose-ranging study was undertaken to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in fALS/SOD1. All participants underwent 3 lumbar punctures, blood draw, clinical assessment of strength, motor function, quality of life, and adverse effect assessments. SOD1 levels were measured in erythrocytes and CSF. Pyrimethamine was measured in plasma and CSF. Appel ALS score, ALS Functional Rating Scale-Revised, and McGill Quality of Life Single-Item Scale were measured at screening, visit 6, and visit 9. We enrolled 32 patients; 24 completed 6 visits (18 weeks), and 21 completed all study visits. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit 6 (p < 0.001) with a mean reduction of 13.5% (95% confidence interval [CI] = 8.4-18.5) and at visit 9 (p < 0.001) with a mean reduction of 10.5% (95% CI = 5.2-15.8). Pyrimethamine is safe and well tolerated in ALS. Pyrimethamine is capable of producing a significant reduction in total CSF SOD1 protein content in patients with ALS caused by different SOD1 mutations. Further long-term studies are warranted to assess clinical efficacy. Ann Neurol 2017;81:837-848. © 2017 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Effects of the peroxisome proliferator clofibric acid on superoxide dismutase expression in the human HepG2 hepatoma cell line.

PubMed

Bécuwe, P; Bianchi, A; Keller, J M; Dauça, M

1999-09-15

We examined the effects of clofibric acid, a peroxisome proliferator, on the production of superoxide radicals, on the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and on the expression of superoxide dismutases (SODs) in the human HepG2 hepatoma cell line. To this end, HepG2 cells were treated for 1 or 5 days with 0.25, 0.50, or 0.75 mM clofibric acid. The production of superoxide radicals was only enhanced in HepG2 cells exposed for 5 days to the different clofibric acid concentrations. However, this overproduction of superoxide radicals was not accompanied by increased rates of lipid peroxidation, as the MDA and 4-HNE levels did not change significantly. Manganese (Mn) SOD activity was increased when HepG2 cells were treated for 1 day with 0.50 or 0.75 mM clofibric acid. For this duration of treatment, no change was observed in total SOD and copper/zinc (Cu/Zn) SOD activities. For a 5-day treatment, total SOD and MnSOD activities as well as the enzyme apoprotein and MnSOD mRNA levels increased whatever the clofibric acid concentration used. This transcriptional induction of the MnSOD gene was correlated with an activation of the activator protein-1 transcription factor for 1 and 5 days of treatment, but was independent of nuclear factor-kappa B and of peroxisome proliferator-activated receptor. On the other hand, the PP exerted very little effect if any on Cu,ZnSOD expression. In contrast to rodent data, PP treatment of human hepatoma cells induces MnSOD expression.

AMELIORATION OF ETHANOL-INDUCED DYSMORPHOGENESIS IN RODENT EMBRYOS IN VITRO USING ADENOVIRAL-MEDIATED EXPRESSION OF CU,ZN-SUPEROXIDE DISMUTASE (SOD1) OR MN-SUPEROXIDE DISMUTASE (SOD2)

EPA Science Inventory

Ethanol produces dysmorphogenesis in offspring when pregnant animals are exposed in vivo (Chaudhuri 2000; Hannigan and Armant, 2000) and by direct exposure of neurulation staged embryos to ethanol in vitro (Kotch et al., 1995; Hunter et al., 1994 ; Thompson and Folb, 1982). The a...

Oxidative stress involvement in Physalis angulata-induced apoptosis in human oral cancer cells.

PubMed

Lee, H-Z; Liu, W-Z; Hsieh, W-T; Tang, F-Y; Chung, J-G; Leung, Henry W-C

2009-03-01

In this report, we investigated the role of oxidative stress in Physalis angulata-induced apoptosis of human oral cancer cells. P. angulata-induced apoptosis was characterized by nuclear morphological changes, membrane blebbing and activation of caspase-9. Exposure of HSC-3 cells to P. angulata caused production of reactive oxygen species and up-regulation of oxidative stress markers heme oxygenase-1 (HO-1), superoxide dismutase (SOD), heat shock protein 70 (HSP70) and caspase-4. Down-regulation of HO-1, SOD and HSP70 proteins expression by attenuation of oxidative stress, pretreatment with glutathione or N-acetylcysteine, significantly decreased P. angulata-triggered cell death. The present study also demonstrated that the mitochondria and the endoplasmic reticulum are the targets of P. angulata in HSC-3 cells. Our results revealed that: (1) reactive oxygen species may play a dominant role in this process, (2) P. angulata induces oxidative stress in HSC-3 cells, (3) P. angulata-initiated apoptosis is caused through oxidative stress-dependent induction of heme oxygenase-1, Cu/Zn SOD and HSP70 proteins expression and (4) antioxidants inhibited P. angulata-induced cell death through inhibition of the proteins expression of HO-1, Cu/Zn SOD and HSP70.

Strain-dependent effects of long-term treatment with melatonin on kainic acid-induced status epilepticus, oxidative stress and the expression of heat shock proteins.

PubMed

Atanasova, Milena; Petkova, Zlatina; Pechlivanova, Daniela; Dragomirova, Petya; Blazhev, Alexander; Tchekalarova, Jana

2013-10-01

Oxidative stress is implicated in the pathogenesis of both hypertension and epileptogenesis, therefore it could be used as a tool for studying co-morbidity of hypertension and epilepsy. Clinical data suggest that melatonin is a potent antioxidant that is effective in the adjunctive therapy of hypertension and neurodegenerative diseases. The present study aimed to explore and compare the efficacy of chronic pretreatment with melatonin infused via subcutaneous osmotic mini-pumps for 14 days (10 mg/kg per day) on kainic acid (KA)-induced status epilepticus, oxidative stress and expression of heat shock protein (HSP) 72 in spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. SHRs showed higher lipid peroxidation (LP) in the frontal cortex and hippocampus and decreased cytosolic superoxide dismutase (SOD/CuZn) production in the frontal cortex compared to Wistar rats. Status epilepticus (SE) induced by KA (12 mg/kg, i.p.) was accompanied by increased LP and expression of HSP 72 in the hippocampus of the two strains and increased SOD/CuZn production in the frontal cortex of SHRs. Melatonin failed to suppress seizure incidence and intensity though the latency for seizure onset was significantly increased in SHRs. Melatonin attenuated the KA-induced increase in the level of LP in the hippocampus both in SHRs and Wistar rats. However, an increased activity in SOD/CuZn and mitochondrial SOD Mn as well as reduced expression of HSP 72 in the hippocampus was observed only in Wistar rats pretreated with melatonin. Taken together, the observed strain differences in the efficacy of chronic melatonin exposure before SE suggest a lack of a direct link between the seizure activity and the markers of oxidative stress and neurotoxicity. © 2013.

Structural analysis and molecular modelling of the Cu/Zn-SOD from fungal strain Humicola lutea 103

NASA Astrophysics Data System (ADS)

Dolashka, Pavlina; Moshtanska, Vesela; Dolashki, Aleksander; Velkova, Lyudmila; Rao, Gita Subba; Angelova, Maria; Betzel, Christian; Voelter, Wolfgang; Atanasov, Boris

2011-12-01

The native form of Cu/Zn-superoxide dismutase, isolated from fungal strain Humicola lutea 103 is a homodimer that coordinates one Cu(2+) and one Zn(2+) per monomer. Cu(2+) and Zn(2+) ions play crucial roles in enzyme activity and structural stability, respectively. It was established that HLSOD shows high pH and temperature stability. Thermostability of the glycosylated enzyme Cu/Zn-SOD, isolated from fungal strain H. lutea 103, was determined by CD spectroscopy. Determination of reversibility toward thermal denaturation for HLSOD allowed several thermodynamic parameters to be calculated. In this communication we report the conditions under which reversible denaturation of HLSOD exists. The narrow range over which the system is reversible has been determined using the strongest test of two important thermodynamic independent variables (T and pH). Combining both these variables, the "phase diagram" was determined, as a result of which the real thermodynamic parameters (Δ Cp, ΔHexp°, and ΔGexp°) was established. Because very narrow pH-interval of transitions we assume they are as result of overlapping of two simple transitions. It was found that Δ Ho is independent from pH with a value of 1.3 kcal/mol and 2.8 kcal/mol for the first and the second transition, respectively. Δ Go was pH-dependent in all studied pH-interval. This means that the transitions are entropically driven, these. Based on this, these processes can be described as hydrophobic rearrangement of the quaternary structure. It was also found that glycosylation does not influence the stability of the enzyme because the carbohydrate chain is exposed on the surface of the molecule.

Mechanisms of TNFalpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice: interaction between TNFalpha and endocannabinoids.

PubMed

Yang, Ying-Ying; Liu, Hongqun; Nam, Soon Woo; Kunos, George; Lee, Samuel S

2010-08-01

Chronic liver disease is associated with endotoxemia, oxidative stress, increased endocannabinoids and decreased cardiac responsiveness. Endocannabinoids activate the tumor necrosis factor-alpha (TNFalpha)-nuclear factor kappaB (NFkappaB) pathway. However, how they interact with each other remains obscure. We therefore aimed to clarify the relationship between the TNFalpha-NFkappaB pathway and endocannabinoids in the pathogenesis of cardiodepression of cholestatic bile duct ligated (BDL) mice. BDL mice with TNFalpha knockout (TNFalpha-/-) and infusion of anti-TNFalpha antibody were used. Cardiac mRNA and protein expression of NFkappaBp65, c-Jun-N-terminal kinases (JNK), p38 mitogen-activated protein kinase (p38MAPK), extracelullar-signal- regulated kinase (ERK), inducible nitric oxide synthase (iNOS), Copper/Zinc and Magnesium-superoxide dismutase (Cu/ Zn- and Mn-SOD), cardiac anandamide, 2-arachidonoylglycerol (2-AG), nitric oxide (NOx) and glutathione, and plasma TNFalpha were measured. The effects of TNFalpha, cannabinoid receptor (CB1) antagonist AM251 and the endocannabinoid reuptake inhibitor UCM707, on the contractility of isolated cardiomyocytes, were assessed. In BDL mice, cardiac mRNA and protein expression of NFkappaBp65, p38MAPK, iNOS, NOx, anandamide, and plasma TNFa were increased, whereas glutathione, Cu/Zn-SOD, and Mn-SOD were decreased. Cardiac contractility was blunted in BDL mice. Anti-TNFa treatment in BDL mice decreased cardiac anandamide and NOx, reduced expression of NFkappaBp65, p38MAPK, and iNOS, enhanced expression of Cu/Zn-SOD and Mn-SOD, increased reductive glutathione and restored cardiomyocyte contractility. TNFa-depressed contractility was worsened by UCM707, whereas AM251 improved contractility. Increased TNFalpha, acting via NFkappaB-iNOS and p38MAPK signaling pathways, plays an important role in the pathogenesis of cardiodepression in BDL mice. TNFalpha also suppressed contractility by increasing oxidative stress and endocannabinoid activity.

Increase of rutin antioxidant activity by generating Maillard reaction products with lysine.

PubMed

Zhang, Ru; Zhang, Bian-Ling; He, Ting; Yi, Ting; Yang, Ji-Ping; He, Bin

2016-06-01

Rutin exists in medicinal herbs, fruits, vegetables, and a number of plant-derived sources. Dietary sources containing rutin are considered beneficial because of their potential protective roles in multiple diseases related to oxidative stresses. In the present study, the change and antioxidation activity of rutin in Maillard reaction with lysine through a heating process were investigated. There is release of glucose and rhamnose that interact with lysine to give Maillard reaction products (MRPs), while rutin is converted to less-polar quercetin and a small quantity of isoquercitrin. Because of their high cell-membrane permeability, the rutin-lysine MRPs increase the free radical-scavenging activity in HepG2 cells, showing cellular antioxidant activity against Cu(2+)-induced oxidative stress higher than that of rutin. Furthermore, the MRPs significantly increased the Cu/Zn SOD (superoxide dismutase) activity and Cu/Zn SOD gene expression of HepG2 cells, consequently enhancing antioxidation activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Weakness of whole muscles in mice deficient in Cu, Zn superoxide dismutase is not explained by defects at the level of the contractile apparatus.

PubMed

Larkin, Lisa M; Hanes, Michael C; Kayupov, Erdan; Claflin, Dennis R; Faulkner, John A; Brooks, Susan V

2013-08-01

Mice deficient in Cu,Zn superoxide dismutase (Sod1 (-/-) mice) demonstrate elevated oxidative stress associated with rapid age-related declines in muscle mass and force. The decline in mass for muscles of Sod1 (-/-) mice is explained by a loss of muscle fibers, but the mechanism underlying the weakness is not clear. We hypothesized that the reduced maximum isometric force (F o) normalized by cross-sectional area (specific F o) for whole muscles of Sod1 (-/-) compared with wild-type (WT) mice is due to decreased specific F o of individual fibers. Force generation was measured for permeabilized fibers from muscles of Sod1 (-/-) and WT mice at 8 and 20 months of age. WT mice were also studied at 28 months to determine whether any deficits observed for fibers from Sod1 (-/-) mice were similar to those observed in old WT mice. No effects of genotype were observed for F o or specific F o at either 8 or 20 months, and no age-associated decrease in specific F o was observed for fibers from Sod1 (-/-) mice, whereas specific F o for fibers of WT mice decreased by 20 % by 28 months. Oxidative stress has also been associated with decreased maximum velocity of shortening (V max), and we found a 10 % lower V max for fibers from Sod1 (-/-) compared with WT mice at 20 months. We conclude that the low specific F o of muscles of Sod1 (-/-) mice is not explained by damage to contractile proteins. Moreover, the properties of fibers of Sod1 (-/-) mice do not recapitulate those observed with aging in WT animals.

Interleukin-1beta and interleukin-6 disturb the antioxidant enzyme system in bovine chondrocytes: a possible explanation for oxidative stress generation.

PubMed

Mathy-Hartert, M; Hogge, L; Sanchez, C; Deby-Dupont, G; Crielaard, J M; Henrotin, Y

2008-07-01

Beside matrix metalloproteinases, reactive oxygen species (ROS) are the main biochemical factors of cartilage degradation. To prevent ROS toxicity, chondrocytes possess a well-coordinated enzymatic antioxidant system formed principally by superoxide dismutases (SODs), catalase (CAT) and glutathione peroxidase (GPX). This work was designed to assess the effects of interleukin (IL)-1beta and IL-6 on the enzymatic activity and gene expression of SODs, CAT and GPX in bovine chondrocytes. Bovine chondrocytes were cultured in monolayer for 4-96 h in the absence or in the presence of IL-1beta (0.018-1.8ng/ml) or IL-6 (10-100 ng/ml). To study signal transduction pathway, inhibitors of mitogen-activated protein kinases (MAPK) (PD98059, SB203580 and SP600125) (5-20 microM) and nuclear factor (NF)-kappaB inhibitors [BAY11-7082 (1-10 microM) and MG132 (0.1-10 microM)] were used. SODs, CAT and GPX enzymatic activities were evaluated in cellular extract by using colorimetric enzymatic assays. Mn SODs, Cu/Zn SOD, extracellular SOD (EC SOD), CAT and GPX gene expressions were quantified by real-time and quantitative polymerase chain reaction (PCR). Mn SOD and GPX activities were dose and time-dependently increased by IL-1beta. In parallel, IL-1beta markedly enhanced Mn SOD and GPX gene expressions, but decreased Cu/Zn SOD, EC SOD and CAT gene expressions. Induction of SOD enzymatic activity and Mn SOD mRNA expression were inhibited by NF-kappaB inhibitors but not by MAPK inhibitors. IL-6 effects were similar but weaker than those of IL-1beta. In conclusion, IL-1beta, and to a lesser extend IL-6, dysregulates enzymatic antioxidant defenses in chondrocyte. These changes could lead to a transient accumulation of H(2)O(2) in mitochondria, and consequently to mitochondria damage. These changes contribute to explain the mitochondrial dysfunction observed in osteoarthritis chondrocytes.

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus

PubMed Central

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; Cabelli, Diane E.; Bruns, Cami K.; Belzer, Carol A.; Gorringe, Andrew R.; Langford, Paul R.; Tabatabai, Louisa B.; Kroll, J. Simon; Tainer, John A.

2015-01-01

ABSTRACT Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats. PMID:26459556

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus.

PubMed

Pratt, Ashley J; DiDonato, Michael; Shin, David S; Cabelli, Diane E; Bruns, Cami K; Belzer, Carol A; Gorringe, Andrew R; Langford, Paul R; Tabatabai, Louisa B; Kroll, J Simon; Tainer, John A; Getzoff, Elizabeth D

2015-12-01

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cu, Zn-Superoxide Dismutase Increases the Therapeutic Potential of Adipose-derived Mesenchymal Stem Cells by Maintaining Antioxidant Enzyme Levels.

PubMed

Yoo, Dae Young; Kim, Dae Won; Chung, Jin Young; Jung, Hyo Young; Kim, Jong Whi; Yoon, Yeo Sung; Hwang, In Koo; Choi, Jung Hoon; Choi, Goang-Min; Choi, Soo Young; Moon, Seung Myung

2016-12-01

In the present study, we investigated the ability of Cu, Zn-superoxide dismutase (SOD1) to improve the therapeutic potential of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) against ischemic damage in the spinal cord. Animals were divided into four groups: the control group, vehicle (PEP-1 peptide and artificial cerebrospinal fluid)-treated group, Ad-MSC alone group, and Ad-MSC-treated group with PEP-1-SOD1. The abdominal aorta of the rabbit was occluded for 30 min in the subrenal region to induce ischemic damage, and immediately after reperfusion, artificial cerebrospinal fluid or Ad-MSCs (2 × 10 5 ) were administered intrathecally. In addition, PEP-1 or 0.5 mg/kg PEP-1-SOD1 was administered intraperitoneally to the Ad-MSC-treated rabbits. Motor behaviors and NeuN-immunoreactive neurons were significantly decreased in the vehicle-treated group after ischemia/reperfusion. Administration of Ad-MSCs significantly ameliorated the changes in motor behavior and NeuN-immunoreactive neuronal survival. In addition, the combination of PEP-1-SOD1 and Ad-MSCs further increased the ameliorative effects of Ad-MSCs in the spinal cord after ischemia. Furthermore, the administration of Ad-MSCs with PEP-1-SOD1 decreased lipid peroxidation and maintained levels of antioxidants such as SOD1 and glutathione peroxidase compared to the Ad-MSC alone group. These results suggest that combination therapy using Ad-MSCs and PEP-1-SOD1 strongly protects neurons from ischemic damage by modulating the balance of lipid peroxidation and antioxidants.

Regulatory and structural properties differentiating the chromosomal and the bacteriophage-associated Escherichia coli O157:H7 Cu, Zn superoxide dismutases.

PubMed

D'Orazio, Melania; Scotti, Raffaella; Nicolini, Laura; Cervoni, Laura; Rotilio, Giuseppe; Battistoni, Andrea; Gabbianelli, Roberta

2008-10-01

Highly virulent enterohemorrhagic Escherichia coli O157:H7 strains possess three sodC genes encoding for periplasmic Cu, Zn superoxide dismutases: sodC, which is identical to the gene present in non-pathogenic E. coli strains, and sodC-F1 and sodC-F2, two nearly identical genes located within lambdoid prophage sequences. The significance of this apparent sodC redundancy in E. coli O157:H7 has not yet been investigated. We report that strains deleted of one or more sodC genes are less resistant than the wild type strain to a challenge with hydrogen peroxide, thus confirming their involvement in the bacterial antioxidant apparatus. To understand if the different sodC genes have truly overlapping functions, we have carried out a comparison of the functional, structural and regulatory properties of the various E. coli O157:H7 SodC enzymes. We have found that the chromosomal and prophagic sodC genes are differentially regulated in vitro. sodC is exclusively expressed in aerobic cultures grown to the stationary phase. In contrast, sodC-F1 and sodC-F2 are expressed also in the logarithmic phase and in anaerobic cultures. Moreover, the abundance of SodC-F1/SodC-F2 increases with respect to that of SodC in bacteria recovered from infected Caco-2 cells, suggesting higher expression/stability of SodC-F1/SodC-F2 in intracellular environments. This observation correlates with the properties of the proteins. In fact, monomeric SodC and dimeric SodC-F1/SodC-F2 are characterized by sharp differences in catalytic activity, metal affinity, protease resistance and stability. Our data show that the chromosomal and bacteriophage-associated E. coli O157:H7 sodC genes have different regulatory properties and encode for proteins with distinct structural/functional features, suggesting that they likely play distinctive roles in bacterial protection from reactive oxygen species. In particular, dimeric SodC-F1 and SodC-F2 possess physico-chemical properties which make these enzymes more suitable than SodC to resist the harsh environmental conditions which are encountered by bacteria within the infected host.

Role of superoxide–nitric oxide interactions in the accelerated age-related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase

PubMed Central

Sakellariou, Giorgos K; Pye, Deborah; Vasilaki, Aphrodite; Zibrik, Lea; Palomero, Jesus; Kabayo, Tabitha; McArdle, Francis; Van Remmen, Holly; Richardson, Arlan; Tidball, James G; McArdle, Anne; Jackson, Malcolm J

2011-01-01

Summary Mice lacking Cu,Zn superoxide dismutase (SOD1) show accelerated, age-related loss of muscle mass. Lack of SOD1 may lead to increased superoxide, reduced nitric oxide (NO), and increased peroxynitrite, each of which could initiate muscle fiber loss. Single muscle fibers from flexor digitorum brevis of wild-type (WT) and Sod1−/− mice were loaded with NO-sensitive (4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, DAF-FM) and superoxide-sensitive (dihydroethidium, DHE) probes. Gastrocnemius muscles were analyzed for SOD enzymes, nitric oxide synthases (NOS), and 3-nitrotyrosine (3-NT) content. A lack of SOD1 did not increase superoxide availability at rest because no increase in ethidium or 2-hydroxyethidium (2-HE) formation from DHE was seen in fibers from Sod1−/− mice compared with those from WT mice. Fibers from Sod1−/− mice had decreased NO availability (decreased DAF-FM fluorescence), increased 3-NT in muscle proteins indicating increased peroxynitrite formation and increased content of peroxiredoxin V (a peroxynitrite reductase), compared with WT mice. Muscle fibers from Sod1−/− mice showed substantially reduced generation of superoxide in response to contractions compared with fibers from WT mice. Inhibition of NOS did not affect DHE oxidation in fibers from WT or Sod1−/− mice at rest or during contractions, but transgenic mice overexpressing nNOS showed increased DAF-FM fluorescence and reduced DHE oxidation in resting muscle fibers. It is concluded that formation of peroxynitrite in muscle fibers is a major effect of lack of SOD1 in Sod1−/− mice and may contribute to fiber loss in this model, and that NO regulates superoxide availability and peroxynitrite formation in muscle. PMID:21443684

QM/MM Calculation of the Enzyme Catalytic Cycle Mechanism for Copper- and Zinc-Containing Superoxide Dismutase.

PubMed

Lintuluoto, Masami; Yamada, Chiaki; Lintuluoto, Juha M

2017-08-03

The entire enzyme catalytic mechanism including the electron and the proton transfers of the copper- and zinc-containing extracellular superoxide dismutase (SOD3) was investigated by using QM/MM method. In the first step, the electron transfer from O 2 ·- to SOD3 occurred without the bond formation between the donor and the acceptor and formed the triplet oxygen molecule and reduced SOD3. In the reduced SOD3, the distorted tetrahedral structure of Cu(I) atom was maintained. The reduction of Cu(II) atom induced the protonation of His113, which bridges between the Cu(II) and Zn(II) atoms in the resting state. Since the protonation of His113 broke the bond between Cu(I) and His113, three-coordinated Cu(I) was formed. Further, we suggest the binding of O 2 ·- formed hydrogen peroxide and the resting state after both the Cu reduction and the protonation of His113. The protonation of His113 caused the conformational change of Arg186 located at the entrance of the reactive site. The electrostatic potential surface around the reactive site showed that Arg186 plays an important role as electrostatic guidance for the negatively charged substrates only after the protonation of His113. The rotation of Arg186 switched the proton supply routes via Glu108 or Glu179 for transferring two protons from the bulk solvent.

Cu/Zn superoxide dismutase and the proton ATPase Pma1p of Saccharomyces cerevisiae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baron, J. Allen; Chen, Janice S.; Culotta, Valeria C., E-mail: vculott1@jhu.edu

2015-07-03

In eukaryotes, the Cu/Zn containing superoxide dismutase (SOD1) plays a critical role in oxidative stress protection as well as in signaling. We recently demonstrated a function for Saccharomyces cerevisiae Sod1p in signaling through CK1γ casein kinases and identified the essential proton ATPase Pma1p as one likely target. The connection between Sod1p and Pma1p was explored further by testing the impact of sod1Δ mutations on cells expressing mutant alleles of Pma1p that alter activity and/or post-translational regulation of this ATPase. We report here that sod1Δ mutations are lethal when combined with the T912D allele of Pma1p in the C-terminal regulatory domain.more » This “synthetic lethality” was reversed by intragenic suppressor mutations in Pma1p, including an A906G substitution that lies within the C-terminal regulatory domain and hyper-activates Pma1p. Surprisingly the effect of sod1Δ mutations on Pma1-T912D is not mediated through the Sod1p signaling pathway involving the CK1γ casein kinases. Rather, Sod1p sustains life of cells expressing Pma1-T912D through oxidative stress protection. The synthetic lethality of sod1Δ Pma1-T912D cells is suppressed by growing cells under low oxygen conditions or by treatments with manganese-based antioxidants. We now propose a model in which Sod1p maximizes Pma1p activity in two ways: one involving signaling through CK1γ casein kinases and an independent role for Sod1p in oxidative stress protection. - Highlights: • In yeast, the anti-oxidant enzyme SOD1 promotes activity of the proton ATPase Pma1p. • Cells expressing a T912D variant of Pma1p are not viable without SOD1. • SOD1 is needed to protect Pma1-T912D expressing cells from severe oxidative damage. • SOD1 activates Pma1p through casein kinase signaling and oxidative stress protection.« less

Effects of Copper on Hemocyte Apoptosis, ROS Production, and Gene Expression in White Shrimp Litopenaeus vannamei.

PubMed

Guo, Hui; Li, Kexu; Wang, Wei; Wang, Chenggui; Shen, Yuchun

2017-10-01

Copper, a common chemical contaminant in aquatic environment, is known to be toxic to aquatic life at high concentrations. In the present study, we evaluated the apoptotic cell ratio and ROS production in hemocytes of the white shrimp Litopenaeus vannamei exposed to 1 or 5 mg L -1 Cu for 0, 3, 6, 12, 24, and 48 h. The expression changes of antioxidant biomarker genes, i.e., copper-zinc superoxide dismutase (Cu-Zn SOD) and catalase (CAT), apoptosis-related genes, i.e., caspase-3 and inhibitor of apoptosis protein (IAP), and a specific biomarker gene of heavy metal pollution, i.e., metallothionein (MT), were also determined in hemocytes. Significant increases in ROS production were observed in both treatment groups at each time points. The apoptotic cell ratios were significantly increased at 6-48 h among shrimp exposed to 1 mg L -1 Cu and at each time points in 5 mg L -1 Cu group. These results indicated that Cu would induce oxidative stress and apoptosis in the hemocyte of L. vannamei. Quantitative real-time PCR analysis revealed that the relative expression levels of Cu-Zn SOD, CAT, caspase-3, IAP, and MT were upregulated in a dose-dependent and time-dependent manner, suggesting the involvement of these genes in stress response against Cu exposure.

Protection of methamphetamine nigrostriatal toxicity by dietary selenium.

PubMed

Kim, H C; Jhoo, W K; Choi, D Y; Im, D H; Shin, E J; Suh, J H; Floyd, R A; Bing, G

1999-12-18

Multiple dose administration of methamphetamine (MA) results in long-lasting toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased production of hydrogen peroxide or other reactive oxygen species in the dopaminergic system. The present study was designed to determine the protective effects of dietary antioxidant selenium on MA-induced neurotoxicity in the nigrostriatal dopaminergic system. Male C57BL/6J mice were fed either selenium-deficient (< 0.01 ppm Se) or selenium-replete (0.2 ppm Se) diets for 90 days. MA treatment decreased the dopamine (DA) levels in the striatum and substantia nigra (SN) of both Se-replete and Se-deficient animals. However, in Se-replete animals, this DA depletion was significantly attenuated in both the striatum and SN. A novel observation is that MA administration resulted in increased activity of Cu,Zn-SOD in the brains of both Se-deficient and Se-replete animals. However, MA administration to Se-deficient animals exhibited a higher Cu,Zn-SOD activity in the nigrostriatal system than the control animals. Elevated malondialdehyde (MDA) levels in the striatum and SN were also observed in Se-deficient MA-treated animals. Se repletion significantly increased the glutathione peroxidase (GPx) activity and the ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) in the MA-treated animals. In conclusion, we have shown that dietary Se attenuated methamphetamine neurotoxicity and that this protection involves GPx-mediated antioxidant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is not yet clear.

Synergistic Effects of GhSOD1 and GhCAT1 Overexpression in Cotton Chloroplasts on Enhancing Tolerance to Methyl Viologen and Salt Stresses

PubMed Central

Luo, Xiaoli; Wu, Jiahe; Li, Yuanbao; Nan, Zhirun; Guo, Xing; Wang, Yixue; Zhang, Anhong; Wang, Zhian; Xia, Guixian; Tian, Yingchuan

2013-01-01

In plants, CuZn superoxide dismutase (CuZnSOD, EC l.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), and catalase (CAT, EC l.11.1.6) are important scavengers of reactive oxygen species (ROS) to protect the cell from damage. In the present study, we isolated three homologous genes (GhSOD1, GhAPX1, and GhCAT1) from Gossypium hirsutum. Overexpressing cassettes containing chimeric GhSOD1, GhAPX1, or GhCAT1 were introduced into cotton plants by Agrobacterium transformation, and overexpressed products of these genes were transported into the chloroplasts by transit peptide, as expected. The five types of transgenic cotton plants that overexpressed GhSOD1, GhAPX1, GhCAT1, GhSOD1 and GhAPX1 stack (SAT), and GhSOD1 and GhCAT1 stack (SCT) were developed. Analyses in the greenhouse showed that the transgenic plants had higher tolerance to methyl viologen (MV) and salinity than WT plants. Interestingly, SCT plants suffered no damage under stress conditions. Based on analyses of enzyme activities, electrolyte leakage, chlorophyll content, photochemical yield (Fv/Fm), and biomass accumulation under stresses, the SCT plants that simultaneously overexpressed GhSOD1 and GhCAT1 appeared to benefit from synergistic effects of two genes and exhibited the highest tolerance to MV and salt stress among the transgenic lines, while the SAT plants simultaneously overexpressing GhSOD1 and GhAPX1 did not. In addition, transgenic plants overexpressing antioxidant enzymes in their chloroplasts had higher tolerance to salt stress than those expressing the genes in their cytoplasms, although overall enzyme activities were almost the same. Therefore, the synergistic effects of GhSOD1 and GhCAT1 in chloroplasts provide a new strategy for enhancing stress tolerance to avoid yield loss. PMID:23335985

Oxidative Stress Induced Age Dependent Meibomian Gland Dysfunction in Cu, Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice

PubMed Central

Ibrahim, Osama M. A.; Dogru, Murat; Matsumoto, Yukihiro; Igarashi, Ayako; Kojima, Takashi; Wakamatsu, Tais Hitomi; Inaba, Takaaki; Shimizu, Takahiko; Shimazaki, Jun; Tsubota, Kazuo

2014-01-01

Purpose The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1 −/−) mouse. Methods Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1 −/− male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild–type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed. Results Corneal vital staining scores in the Sod1 −/− mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1 −/− mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1 −/− mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1 −/− mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1 −/− mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1 −/− mice. Conclusions Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1 −/− mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations. PMID:25036096

Models for the mechanism for activating copper-zinc superoxide dismutase in the absence of the CCS Cu chaperone in Arabidopsis.

PubMed

Huang, Chien-Hsun; Kuo, Wen-Yu; Jinn, Tsung-Luo

2012-03-01

Copper-zinc superoxide dismutase (CuZnSOD; CSD) is an important antioxidant enzyme for oxidative stress protection. To date, two activation pathways have been identified in many species. One requiring the CCS, Cu chaperone for SOD, to insert Cu and activate CSD (referred to as CCS-dependent pathway), and the other works independently of CCS (referred to as CCS-independent pathway). In our previous study, we suggest an unidentified factor will work with glutathione (GSH) for CSD activation in the absence of the CCS. Here, two models of the CCS-independent mechanism are proposed. The role of the unidentified factor may work as a scaffold protein, which provides a platform for the CSD protein and Cu-GSH to interact, or as a Cu carrier, which itself can bind Cu and interact with CSD proteins. We also suggest that the CSD protein conformation at C-terminal is important in providing a docking site for unidentified factor to access.

Astaxanthin intake attenuates muscle atrophy caused by immobilization in rats.

PubMed

Shibaguchi, Tsubasa; Yamaguchi, Yusuke; Miyaji, Nobuyuki; Yoshihara, Toshinori; Naito, Hisashi; Goto, Katsumasa; Ohmori, Daijiro; Yoshioka, Toshitada; Sugiura, Takao

2016-08-01

Astaxanthin is a carotenoid pigment and has been shown to be an effective inhibitor of oxidative damage. We tested the hypothesis that astaxanthin intake would attenuate immobilization-induced muscle atrophy in rats. Male Wistar rats (14-week old) were fed for 24 days with either astaxanthin or placebo diet. After 14 days of each experimental diet intake, the hindlimb muscles of one leg were immobilized in plantar flexion position using a plaster cast. Following 10 days of immobilization, both the atrophic and the contralateral plantaris muscles were removed and analyzed to determine the level of muscle atrophy along with measurement of the protein levels of CuZn-superoxide dismutase (CuZn-SOD) and selected proteases. Compared with placebo diet animals, the degree of muscle atrophy in response to immobilization was significantly reduced in astaxanthin diet animals. Further, astaxanthin supplementation significantly prevented the immobilization-induced increase in the expression of CuZn-SOD, cathepsin L, calpain, and ubiquitin in the atrophied muscle. These results support the postulate that dietary astaxanthin intake attenuates the rate of disuse muscle atrophy by inhibiting oxidative stress and proteolysis via three major proteolytic pathways. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Evaluating the influence of National Research Council levels of copper, iron, manganese, and zinc using organic (Bioplex) minerals on resulting tissue mineral concentrations, metallothionein, and liver antioxidant enzymes in grower-finisher swine diets.

PubMed

Gowanlock, D W; Mahan, D C; Jolliff, J S; Hill, G M

2015-03-01

Graded levels of a trace mineral premix containing an organic (Bioplex) source of Cu, Fe, Mn, and Zn was evaluated with additional treatments containing organic Zn or Fe. Grower-finisher pigs were fed from 25 to 115 kg BW. The number of pigs in the experiment, the breeding/genetics of the pigs, the management, and the average age of the pigs were previously reported. The experiment was conducted as a randomized complete block design in 7 replicates. Treatments were 1) basal diet without supplemental Cu, Fe, Mn, and Zn; 2) basal diet + 2.5 mg/kg Cu, 50 mg/kg Fe, 1.5 mg/kg Mn, and 40 mg/kg Zn (50% NRC); 3) basal diet + 5 mg/kg Cu, 100 mg/kg Fe, 3 mg/kg Mn, and 80 mg/kg Zn (100% NRC); 4) basal diet + 25 mg Zn/kg; 5) basal diet + 50 mg Zn/kg; and 6) basal diet + 50 mg Fe/kg. Selenium and I were added to all diets at 0.3 and 0.14 mg/kg, respectively. Diets were composed of corn-soybean meal, dicalcium phosphate, and limestone with phytase added to enhance mineral availability. Three pigs per pen were bled at 55, 80, and 115 kg BW and plasma was analyzed for microminerals. When the average replicate BW was 115 kg, 3 pigs per pen of an equal gender ratio were killed. The liver, kidney, and heart were removed and analyzed for microminerals. Liver, duodenum, and jejunal metallothionein and the antioxidant enzymes in the liver containing these microminerals were determined. The results demonstrated that plasma minerals were unaffected at the 3 BW intervals. Liver and duodenum metallothionein protein were greater ( < 0.05) as dietary micromineral levels increased but jejunum metallothionein did not change as microminerals increased. The activity of Cu/Zn superoxide dismutase (SOD) was not affected as the levels of the micromineral increased, whereas the activity of Mn SOD increased slightly ( < 0.05) to the 50% NRC treatment level. Liver Zn (relative and total) increased ( < 0.05) as dietary micromineral levels increased and also when Zn was added singly to the diet. Liver, kidney, and heart Cu and Mn concentrations were similar at the various micromineral levels. The activities of liver enzymes containing graded levels of Zn were not affected by dietary microminerals at 115 kg BW. These results indicate that the supplemental levels of Cu, Fe, and Mn were not necessary for grower-finisher pigs and that these innate microminerals in a corn-soybean meal diet were adequate, whereas a need for supplemental Zn was demonstrated.

cIAPs promote the proteasomal degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis.

PubMed

Choi, Jin Sun; Kim, Kidae; Lee, Do Hee; Cho, Sayeon; Ha, Jae Du; Park, Byoung Chul; Kim, Sunhong; Park, Sung Goo; Kim, Jeong-Hoon

2016-11-18

Although the ubiquitin-proteasome system is believed to play an important role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS), caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1), the mechanism of how mutant SOD1 protein is regulated in cells is still poorly understood. Here we have demonstrated that cellular inhibitor of apoptosis proteins (cIAPs) are specifically associated with FALS-linked mutant SOD1 (mSOD1) and that this interaction promotes the ubiquitin-dependent proteasomal degradation of mutant SOD1. By utilizing cumate inducible SOD1 cells, we also showed that knock-down or pharmacologic depletion of cIAPs leads to H 2 O 2 induced cytotoxicity in mSOD1 expressing cells. Altogether, our results reveal a novel role of cIAPs in FALS-associated mutant SOD1 regulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction.

PubMed

Gill, Tejpal; Levine, Alan D

2013-09-06

T cell receptor (TCR)-initiated signal transduction is reported to increase production of intracellular reactive oxygen species, such as superoxide (O2˙(-)) and hydrogen peroxide (H2O2), as second messengers. Although H2O2 can modulate signal transduction by inactivating protein phosphatases, the mechanism and the subcellular localization of intracellular H2O2 as a second messenger of the TCR are not known. The antioxidant enzyme superoxide dismutase (SOD) catalyzes the dismutation of highly reactive O2˙(-) into H2O2 and thus acts as an intracellular generator of H2O2. As charged O2˙(-) is unable to diffuse through intracellular membranes, cells express distinct SOD isoforms in the cytosol (Cu,Zn-SOD) and mitochondria (Mn-SOD), where they locally scavenge O2˙(-) leading to production of H2O2. A 2-fold organelle-specific overexpression of either SOD in Jurkat T cell lines increases intracellular production of H2O2 but does not alter the levels of intracellular H2O2 scavenging enzymes such as catalase, membrane-bound peroxiredoxin1 (Prx1), and cytosolic Prx2. We report that overexpression of Mn-SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal transduction molecules Lck, LAT, ZAP70, PLCγ1, and SLP76 within 1 min of TCR cross-linking. This increase in mitochondrial H2O2 specifically modulates MAPK signaling through the JNK/cJun pathway, whereas overexpressing Cu,Zn-SOD had no effect on any of these TCR-mediated signaling molecules. As mitochondria translocate to the immunological synapse during TCR activation, we hypothesize this translocation provides the effective concentration of H2O2 required to selectively modulate downstream signal transduction pathways.

Virtual electrochemical nitric oxide analyzer using copper, zinc superoxide dismutase immobilized on carbon nanotubes in polypyrrole matrix.

PubMed

Madasamy, Thangamuthu; Pandiaraj, Manickam; Balamurugan, Murugesan; Karnewar, Santosh; Benjamin, Alby Robson; Venkatesh, Krishna Arun; Vairamani, Kanagavel; Kotamraju, Srigiridhar; Karunakaran, Chandran

2012-10-15

In this work, we have designed and developed a novel and cost effective virtual electrochemical analyzer for the measurement of NO in exhaled breath and from hydrogen peroxide stimulated endothelial cells using home-made potentiostat. Here, data acquisition system (NI MyDAQ) was used to acquire the data from the electrochemical oxidation of NO mediated by copper, zinc superoxide dismutase (Cu,ZnSOD). The electrochemical control programs (graphical user-interface software) were developed using LabVIEW 10.0 to sweep the potential, acquire the current response and process the acquired current signal. The Cu,ZnSOD (SOD1) immobilized on the carbon nanotubes in polypyrrole modified platinum electrode was used as the NO biosensor. The electrochemical behavior of the SOD1 modified electrode exhibited the characteristic quasi-reversible redox peak at the potential, +0.06 V vs. Ag/AgCl. The biological interferences were eliminated by nafion coated SOD1 electrode and then NO was measured selectively. Further, this biosensor showed a wide linear range of response over the concentration of NO from 0.1 μM to 1 mM with a detection limit of 0.1 μM and high sensitivity of 1.1 μA μM(-1). The electroanalytical results obtained here using the developed virtual electrochemical instrument were also compared with the standard cyclic voltammetry instrument and found in agreement with each other. Copyright © 2012 Elsevier B.V. All rights reserved.

Association between enzymatic and non-enzymatic antioxidant defense mechanism with apolipoprotein E genotypes in Alzheimer disease.

PubMed

Kharrazi, Hadi; Vaisi-Raygani, Asad; Rahimi, Zohreh; Tavilani, Haidar; Aminian, Mahdi; Pourmotabbed, Tayebeh

2008-08-01

There are evidence suggesting that APOE-varepsilon4 allele play an important role in the pathogenesis of Alzheimer's disease (AD) by reducing peripheral levels and activities of a broad spectrum of nonenzymatic and enzymatic antioxidants systems. However, the link between APOE genotype, oxidative stress, and AD has yet to be established. In this study we examined whether antioxidant defense mechanism exacerbates the risk of AD in individual carrying APOE-varepsilon4 allele in a population from Tehran, Iran. We determined the enzymatic activities of the erythrocyte Cu-Zn superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and serum level of total antioxidant status(TAS) in various APOE genotypes in 91 patients with AD and 91 healthy subjects as control group (age and sex-matched). The results showed that the TAS level and the activities of enzymatic antioxidants CAT and GSH-Px were significantly lower and the SOD activity was significantly higher in AD patients compared to controls. The AD patients with APOE-varepsilon4 allele genotype had significantly lower serum TAS concentration and lower erythrocytes GSH-Px and CAT activities (p=0.001) but significantly higher erythrocytes Cu-Zn SOD activity (p=0.001) than the non-APOE-varepsilon4 carrier AD and the control group. In addition, the association observed between the factors involved in an antioxidant defense mechanism and APOE-varepsilon4 allele in AD increased with age of the subjects. These data indicate that the reduced serum level of TAS and activity of CAT, GSH-Px and increased SOD exacerbate the risk of AD in individuals carrying APOE-varepsilon4 allele. The reduced antioxidants defense in APOE-varepsilon4 allele carrier may contribute to beta-amyloidosis. This effect, however, is more pronounced in the AD patients older than 75 years of age. This suggests that a therapeutic modality should be considered for these subjects.

Effects of varying dietary iodine supplementation levels as iodide or iodate on thyroid status as well as mRNA expression and enzyme activity of antioxidative enzymes in tissues of grower/finisher pigs.

PubMed

Li, Qimeng; Mair, Christiane; Schedle, Karl; Hellmayr, Isabella; Windisch, Wilhelm

2013-02-01

The objective of this study was to investigate the influence of high dietary iodine supply and different iodine sources on thyroid status and oxidative stress in target tissues of the thyroid hormones in fattening pigs. Eighty castrates (body weight: 33.3 ± 0.4 kg) were randomly allotted into five different treatments: The control diet contained 150 μg I/kg as KI, the other feeding groups were supplemented with 4,000 μg I/kg (as KI and KIO(3)) and 10,000 μg I/kg (as KI and KIO(3)), respectively. The mRNA expression levels of sodium/iodide symporter (NIS) and key antioxidant enzymes (Cu/Zn SOD, CAT, GPx) were analyzed in thyroid gland, liver, kidney, muscle, and adipose tissue sampled during slaughter. Furthermore, antioxidant enzyme activities and the effect on lipid peroxidation (MDA) were determined in liver and muscle. In thyroid gland, a significant downregulation of NIS and Cu/Zn SOD mRNA expression was observed in high-iodine groups. In liver, a source effect on the mRNA expression of Cu/Zn SOD between KI and KIO(3) at 4,000 μg I/kg was shown. In contrast, not SOD but GPx activity was affected by iodine source with strongest downregulation in high KIO(3) group. In muscle, GPx activity was affected by both iodine source and dose, showing stronger downregulation in KI groups. In kidney and adipose tissue, oxidative stress parameters showed no or only unsystematic changes. However, variation in iodine supply had no effect on MDA concentrations. NIS expression was significantly decreased with increased iodine supplementation, which is to ensure the thyroid gland function. However, the alleviating effect of iodine supplementation observed in antioxidant enzyme mRNA expression and activity did not reflect on the lipid peroxide level.

Syntheses, structures, and properties of imidazolate-bridged Cu(II)-Cu(II) and Cu(II)-Zn(II) dinuclear complexes of a single macrocyclic ligand with two hydroxyethyl pendants.

PubMed

Li, Dongfeng; Li, Shuan; Yang, Dexi; Yu, Jiuhong; Huang, Jin; Li, Yizhi; Tang, Wenxia

2003-09-22

The imidazolate-bridged homodinuclear Cu(II)-Cu(II) complex, [(CuimCu)L]ClO(4).0.5H(2)O (1), and heterodinuclear Cu(II)-Zn(II) complex, [(CuimZnL(-)(2H))(CuimZnL(-)(H))](ClO(4))(3) (2), of a single macrocyclic ligand with two hydroxyethyl pendants, L (L = 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22,2,2,2(11,14)]triaconta-1,11,13,24,27,29-hexaene), have been synthesized as possible models for copper-zinc superoxide dismutase (Cu(2),Zn(2)-SOD). Their crystal structures analyzed by X-ray diffraction methods have shown that the structures of the two complexes are markedly different. Complex 1 crystallizes in the orthorhombic system, containing an imidazolate-bridged dicopper(II) [Cu-im-Cu](3+) core, in which the two copper(II) ions are pentacoordinated by virtue of an N4O environment with a Cu.Cu distance of 5.999(2) A, adopting the geometry of distorted trigonal bipyramid and tetragonal pyramid, respectively. Complex 2 crystallizes in the triclinic system, containing two similar Cu-im-Zn cores in the asymmetric unit, in which both the Cu(II) and Zn(II) ions are pentacoordinated in a distorted trigonal bipyramid geometry, with the Cu.Zn distance of 5.950(1)/5.939(1) A, respectively. Interestingly, the macrocyclic ligand with two arms possesses a chairlike (anti) conformation in complex 1, but a boatlike (syn) conformation in complex 2. Magnetic measurements and ESR spectroscopy of complex 1 have revealed the presence of an antiferromagnetic exchange interaction between the two Cu(II) ions. The ESR spectrum of the Cu(II)-Zn(II) heterodinuclear complex 2 displayed a typical signal for mononuclear trigonal bipyramidal Cu(II) complexes. From pH-dependent ESR and electronic spectroscopic studies, the imidazolate bridges in the two complexes have been found to be stable over broad pH ranges. The cyclic voltammograms of the two complexes have been investigated. Both of the two complexes can catalyze the dismutation of superoxide and show rather high activity.

Effects of dietary zinc on gene expression of antioxidant enzymes and heat shock proteins in hepatopancreas of abalone Haliotis discus hannai.

PubMed

Wu, Chenglong; Zhang, Wenbing; Mai, Kangsen; Xu, Wei; Zhong, Xiaoli

2011-06-01

The expression patterns of different genes encoding antioxidant enzymes and heat shock proteins were investigated, in present study, by real-time quantitative PCR in the hepatopancreas of abalone Haliotis discus hannai fed with different levels of dietary zinc (6.69, 33.8, 710.6 and 3462.5 mg/kg) for 20 weeks. The antioxidant enzymes include Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase (CAT), mu-glutathione-s-transferase (mu-GST) and thioredoxin peroxidase (TPx). The results showed that the mRNA expression of these antioxidant enzymes increased and reached the maximum at the dietary zinc level of 33.8 mg/kg, and then dropped progressively. Expression levels of the heat shock proteins (HSP26, HSP70 and HSP90) firstly increased at 33.8 mg/kg dietary Zn level, and reached to the maximum at 710.6 mg/kg, then dropped at 3462.5 mg/kg (p<0.05). Excessive dietary Zn (710.6 and 3462.5 mg/kg) significantly increases the Zn content and significantly decreases the total antioxidant capacity (T-AOC) in hepatopancreas (p<0.05). These findings showed that dietary Zn (33.8 mg/kg) could highly trigger the expression levels of antioxidant enzymes and heat shock proteins, but excessive dietary Zn (710.6 and 3462.5 mg/kg) induces a high oxidative stress in abalone. Copyright © 2011 Elsevier Inc. All rights reserved.

Acquisition of pro-oxidant activity of fALS-linked SOD1 mutants as revealed using circular dichroism and UV-resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Fujimaki, Nobuhiro; Nishiya, Ken; Miura, Takashi; Nakabayashi, Takakazu

2016-11-01

The acquisition of pro-oxidant activity of the mutated form of human Cu, Zn-superoxide dismutase (SOD1) has been investigated to clarify the relationship between mutations in SOD1 and the pathogenesis of amyotrophic lateral sclerosis (ALS). Ala4 → Val (A4V) and Gly93 → Ala (G93A) mutants, which are representative ALS-linked SOD1 mutants, have been found to exhibit both the denaturation and the gain of pro-oxidant activity after incubation in the apo-form at a physiological condition of 37 °C and pH 7.4 and the rebinding of Cu2+. These characteristics are similar to those previously reported for the His43 → Arg (H43R) mutant. UV-resonance Raman spectra indicated that the coordination structure of the Cu-binding site catalyzing the oxidation reaction is the same among the denatured A4V, G93A, and H43R. Since wild-type SOD1 does not exhibit the denaturation in its apo-form at 37 °C and pH 7.4, the instability of the protein structure due to mutation can be considered as a significant factor that induces the denaturation and the subsequent pro-oxidant activity.

Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice

PubMed Central

Csiszar, Anna; Labinskyy, Nazar; Perez, Viviana; Recchia, Fabio A.; Podlutsky, Andrej; Mukhopadhyay, Partha; Losonczy, Gyorgy; Pacher, Pal; Austad, Steven N.; Bartke, Andrzej; Ungvari, Zoltan

2008-01-01

Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O2•− and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O2•− and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu,Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O2•− and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu,Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress. PMID:18757483

Evaluation of the antioxidant effects of melatonin on the larynx mucosa of rats exposed to environmental tobacco smoke.

PubMed

Donmez, Z; Yigit, Ö; Bilici, S; Dursun, N; Gul, M; Dastan, S D; Uzun, H

2016-06-01

This study's aim was to investigate the effect of melatonin in terms of mitigating the effects of smoking on the laryngeal mucosa of rats exposed to environmental tobacco smoke. Rats were divided into four groups: Melatonin + Smoking group exposed to smoke with melatonin; Smoking group exposed to smoke without melatonin; Saline group not exposed to smoke without melatonin; Melatonin group not exposed to smoke with melatonin. CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were evaluated in plasma and tissues. Tissues were also examined the changes of squamous hyperplasia, keratosis, parakeratosis and epithelial hyperplasia by light microscope and the ultrastructural changes by electron microscope. Tissue SOD, CAT and GSH-Px activities were significantly higher in Saline and Melatonin groups than Melatonin + Smoking and Smoking groups. Plasma CuZn-SOD and CAT activities were significantly higher in Saline and Melatonin groups than Smoking group. Plasma GSH-Px showed no significant difference. The rate of epithelial hyperplasia was significantly higher in Smoking group than the other groups. The rate of parakeratosis was significantly higher in Smoking group than the other groups. The epithelial cells in Melatonin + Smoking group displayed, normal cell structure similar to those in Saline group under electron microscope. The study shows that smoking induces substantial pathological changes in the laryngeal mucosa and melatonin may have some beneficial effects in partially reversing smoking-induced laryngeal injury by inducing the expression of antioxidants; biochemical and histological outcomes also support these findings due to preventing tissue damage in laryngeal mucosa exposed to smoke. © 2015 John Wiley & Sons Ltd.

Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haley, Gwendolen E.; Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR; Villasana, Laura

2012-11-01

Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles ({epsilon}2, {epsilon}3, and {epsilon}4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of {sup 56}Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after {sup 56}Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, wemore » assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis. Results: In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice. Conclusions: The short-term effects of {sup 56}Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.« less

Pro-inflammatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with obesity in Egyptian non-diabetic obese children and adolescents.

PubMed

Habib, Salem A; Saad, Entsar A; Elsharkawy, Ashraf A; Attia, Zeinab R

2015-09-01

To investigate the inter-relationships between adipocytokines, oxidative stress, insulin, Zn and Cu and obesity among Egyptian obese non-diabetic children and adolescents. 72 obese children and adolescents of both sexes (5-17 years) were recruited for the study. 40 healthy normal non-obese persons of matched ages and sexes were used as control group. Lipid profile, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and leptin levels were measured. Malondialdehyde (MDA) and reduced glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were estimated. Micronutrients (Zn and Cu) concentrations in addition to insulin and fasting blood sugar (FBS) levels were also evaluated. Estimation of insulin resistance (homeostatic model assessment (HOMA-IR)) was derived from FBS measurements. Significant elevations (P<0.001) in TNF-α, IL-6, leptin, MDA, Cu and FBS levels and significant decreases (P<0.001) in GSH, Zn levels and SOD activity were detected among obese individuals as compared with control group. Insulin and triglyceride levels were significantly increased in obese male children and HDL-cholesterol level was increased significantly in obese adolescent females compared to controls. However, total cholesterol and LDL-cholesterol levels were significantly high in all obese cases as compared with controls. Insulin resistance was detected in 100% of the patients. We concluded that obesity with pro-inflammatory adipocytokines and hypozincemia together by many mechanisms participate in excessive oxidative stress and are highly associated with inflammation and the development of obesity-related complications. Obesity represents a critical risk factor for development of insulin resistance status. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Assessment of ligand binding at a site relevant to SOD1 oxidation and aggregation.

PubMed

Manjula, Ramu; Wright, Gareth S A; Strange, Richard W; Padmanabhan, Balasundaram

2018-05-01

Cu/Zn superoxide dismutase-1 (SOD1) mutations are causative for a subset of amyotrophic lateral sclerosis (ALS) cases. These mutations lead to structural instability, aggregation and ultimately motor neuron death. We have determined crystal structures of SOD1 in complex with a naphthalene-catechol-linked compound which binds with low micro-molar affinity to a site important for oxidative damage-induced aggregation. SOD1 Trp32 oxidation is indeed significantly inhibited by ligand binding. Our work shows how compound linking can be applied successfully to ligand interactions on the SOD1 surface to generate relatively good binding strength. The ligand, positioned in a region important for SOD1 fibrillation, offers the possibility that it, or a similar compound, could prevent the abnormal self-association that drives SOD1 toxicity in ALS. © 2018 Federation of European Biochemical Societies.

Zymographic Method for Distinguishing Different Classes of Superoxide Dismutases in Plants.

PubMed

Jamdhade, Ashwini R; Sunkar, Ramanjulu; Hivrale, Vandana K

2017-01-01

In plants, especially in chloroplasts, superoxide radical is generated when an electron is transferred to dimolecular O 2 due to decreased activity of Photosystem I. The superoxide (O 2 - ) radical accumulation is more rampant in plants exposed to abiotic stresses due to oxidation of photosystem components. Excessive superoxide radical accumulation will lead to oxidative damage to the cellular macromolecules. The ubiquitous superoxide dismutases (SODs) represent critical enzymatic antioxidant system present in cells, which can catalyze the disproportion of superoxide (O 2 - ) radical rapidly into hydrogen peroxide (H 2 O 2 ) and molecular oxygen. Depending on the metal cofactor present, the plant SODs are classified into Cu/ZnSOD, MnSOD, and FeSOD. The activity of SODs can be quantified zymographically. Additionally, using this method, different classes of SODs can be distinguished by using H 2 O 2 , KCN, and NaN 3.

Alpha-lipoic acid affects the oxidative stress in various brain structures in mice with methionine and choline deficiency.

PubMed

Veskovic, Milena; Mladenovic, Dusan; Jorgacevic, Bojan; Stevanovic, Ivana; de Luka, Silvio; Radosavljevic, Tatjana

2015-04-01

Deficiency in methionine or choline can induce oxidative stress in various organs such as liver, kidney, heart, and brain. This study was to examine the effects of alpha-lipoic acid (LA) on oxidative stress induced by methionine and choline deficiency (MCD) in several brain structures. Male mice C57BL/6 (n = 28) were divided into four groups: (1) control - continuously fed with standard chow; (2) LA - fed with standard chow and receiving LA; (3) MCD2 - fed with MCD diet for two weeks, and (4) MCD2+LA - fed with MCD diet for two weeks and receiving LA (100 mg/kg/day intraperitonealy [i.p.]). Brain tissue (cortex, hypothalamus, striatum and hippocampus) was taken for determination of oxidative stress parameters. MCD diet induced a significant increase in malondialdehyde and NOx concentration in all brain regions, while LA restored their content to normal values. Similar to this, in MCD2 group, activity of total SOD, MnSOD, and Cu/ZnSOD was reduced by MCD diet, while LA treatment improved their activities in all brain structures. Besides, in MCD2 group a decrease in catalase activity in cortex and GSH content in hypothalamus was evident, while LA treatment induced an increase in catalase activity in cortex and striatum and GSH content in hypothalamus. LA treatment can significantly reduce lipid peroxidation and nitrosative stress, caused by MCD diet, in all brain regions by restoring antioxidant enzymes activities, predominantly total SOD, MnSOD, and Cu/ZnSOD, and to a lesser extent by modulating catalase activity and GSH content. LA supplementation may be used in order to prevent brain oxidative injury induced by methionine and choline deficiency. © 2014 by the Society for Experimental Biology and Medicine.

Molecular Cloning, Characterization and Predicted Structure of a Putative Copper-Zinc SOD from the Camel, Camelus dromedarius

PubMed Central

Ataya, Farid S.; Fouad, Dalia; Al-Olayan, Ebtsam; Malik, Ajamaluddin

2012-01-01

Superoxide dismutase (SOD) is the first line of defense against oxidative stress induced by endogenous and/or exogenous factors and thus helps in maintaining the cellular integrity. Its activity is related to many diseases; so, it is of importance to study the structure and expression of SOD gene in an animal naturally exposed most of its life to the direct sunlight as a cause of oxidative stress. Arabian camel (one humped camel, Camelus dromedarius) is adapted to the widely varying desert climatic conditions that extremely changes during daily life in the Arabian Gulf. Studying the cSOD1 in C. dromedarius could help understand the impact of exposure to direct sunlight and desert life on the health status of such mammal. The full coding region of a putative CuZnSOD gene of C. dromedarius (cSOD1) was amplified by reverse transcription PCR and cloned for the first time (gene bank accession number for nucleotides and amino acids are JF758876 and AEF32527, respectively). The cDNA sequencing revealed an open reading frame of 459 nucleotides encoding a protein of 153 amino acids which is equal to the coding region of SOD1 gene and protein from many organisms. The calculated molecular weight and isoelectric point of cSOD1 was 15.7 kDa and 6.2, respectively. The level of expression of cSOD1 in different camel tissues (liver, kidney, spleen, lung and testis) was examined using Real Time-PCR. The highest level of cSOD1 transcript was found in the camel liver (represented as 100%) followed by testis (45%), kidney (13%), lung (11%) and spleen (10%), using 18S ribosomal subunit as endogenous control. The deduced amino acid sequence exhibited high similarity with Cebus apella (90%), Sus scrofa (88%), Cavia porcellus (88%), Mus musculus (88%), Macaca mulatta (87%), Pan troglodytes (87%), Homo sapiens (87%), Canis familiaris (86%), Bos taurus (86%), Pongo abelii (85%) and Equus caballus (82%). Phylogenetic analysis revealed that cSOD1 is grouped together with S. scrofa. The predicted 3D structure of cSOD1 showed high similarity with the human and bovine CuZnSOD homologues. The Root-mean-square deviation (rmsd) between cSOD1/hSOD1 and cSOD1/bSOD1 superimposed structure pairs were 0.557 and 0.425 A. The Q-score of cSOD1-hSOD1 and cSOD1-bSOD1 were 0.948 and 0.961, respectively. PMID:22312292

Effect of Allium flavum L. and Allium melanantherum Panč. Extracts on Oxidative DNA Damage and Antioxidative Enzymes Superoxide Dismutase and Catalase.

PubMed

Mitić-Ćulafić, Dragana; Nikolić, Biljana; Simin, Nataša; Jasnić, Nebojša; Četojević-Simin, Dragana; Krstić, Maja; Knežević-Vukčević, Jelena

2016-03-01

Allium flavum L. and Allium melanantherum Panč. are wild growing plants used in traditional diet in Balkan region. While chemical composition and some biological activities of A. flavum have been reported, A. melanantherum, as an endemic in the Balkan Peninsula, has never been comprehensively examined. After chemical characterization of A. melanantherum, we examined the protective effect of methanol extracts of both species against t-butyl hydro-peroxide (t-BOOH)-induced DNA damage and mutagenesis. The bacterial reverse mutation assay was performed on Escherichia coli WP2 oxyR strain. DNA damage was monitored in human fetal lung fibroblasts (MRC-5) with alkaline comet assay. Obtained results indicated that extracts reduced t-BOOH-induced DNA damage up to 70 and 72% for A. flavum and A. melanantherum extract, respectively, and showed no effect on t-BOOH-induced mutagenesis. Since the results indicated modulatory effect on cell-mediated antioxidative defense, the effect of extracts on total protein content, and superoxide dismutase (SOD) and catalase (CAT) amounts and activities were monitored. Both extracts increased total protein content, while the increase of enzyme amount and activity was obtained only with A. melanantherum extract and restricted to CAT. The activity of CuZnSOD family was not affected, while SOD1 and SOD2 amounts were significantly decreased, indicating potential involvement of extracellular CuZnSOD. Obtained results strongly support the traditional use of A. flavum and A. melanantherum in nutrition and recommend them for further study.

[The evaluation of selected oxidative stress parameters in patients after radioiodine treatment of hyperthyroidism].

PubMed

Owczarek, Tomasz; Kowalczyk, Edward; Poliwczak, Adam Rafał; Bała, Agnieszka; Broncel, Marlena

2012-06-01

Oxidative stress is an important factor of the hyperthyroidism pathogenesis. The radioiodine therapy is an approved treatment method of this common disease and it is connected with exposure to ionizing radiation, which induces increased generation of reactive oxygen species in patient's organism. The aim of the study was to estimate the selected oxidative stress parameters in hyperthyroid patients, initially treated with thiamazole and subsequently with radioiodine. The evaluated parameters were the activity of superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GPx) in erythrocytes as well as the level of total antioxidative status (TAS) in plasma. In the study participated 29 healthy volunteers and 27 hyperthyroid patients, treated with thiamazole and prepared for radioiodine therapy. The antioxidant enzymes activity and the level of TAS were measured before administration of radioiodine therapeutic dose (average 18.47 +/- 8.81 mCi) as well as 30 days after treatment and achieving euthyreosis. Hyperthyroid patients prepared with thiamazole for radioiodine therapy demonstrated higher GPx activity (p < 0.0001) and lower TAS level (p < 0.0001) than healthy people. Patients, who become euthyroid after 30 days from radioiodine therapy, were characterised by the increased activity of CAT (p < 0.05) and GPx (p < 0.05) as well as the higher level of TAS (p < 0.05). Patients after radioiodine treatment in comparison to the control group had the same activity of CAT and the level of TAS, although the activity of CuZn-SOD (p < 0.05) and GPx (p < 0.0001) occurred higher than in the control group. Moreover patients with hyperthyroidism before radioiodine treatment showed positive correlation between the level of TSH and TAS, whereas after radioiodine therapy they demonstrated positive correlation between the level of TSH and the activity of CuZn-SOD, CAT and GPx. However, there was no statistically significant correlation between the quantity of administrated radioiodine dose and the value of estimated oxidative stress parameters. The results of the study show the occurrence of oxidative stress in hyperthyroid patients prepared with thiamazole to radioiodine therapy. Euthyreosis achieved by radioiodine treatment effected on normalisation of the activity of CAT and the level of TAS, although the activity of CuZn-SOD and GPx stayed increased. After the analysis of correlation between TSH level, radioiodine dose and measured parameters we can conclude that the intensity of oxidative stress more depends on current thyreometabolic state than on the therapeutic method applied.

Exogenous superoxide dismutase may lose its antidotal ability on rice leaves

USDA-ARS?s Scientific Manuscript database

Leaf diffusates of the resistant rice cultivars suppressed spore germination of blast fungus (Magnaporthe grisea). Bovine Cu-Zn superoxide dismutase (SOD) added to the diffusate abolished its toxicity. However, the enzyme added to the inoculum did not affect the toxicity of the diffusate. Even the s...

Cissus quadrangularis ethanol extract upregulates superoxide dismutase, glutathione peroxidase and endothelial nitric oxide synthase expression in hydrogen peroxide-injured human ECV304 cells.

PubMed

Sapsrithong, Tarat; Kaewprem, Weeraya; Tongumpai, Sarunya; Nusuetrong, Punnee; Meksuriyen, Duangdeun

2012-09-28

Cissus quadrangularis has been widely used in traditional medicine for the treatment of hemorrhoid. However, the detailed mechanism of antioxidant defense of C. quadrangularis in endothelial cells under oxidative stress remains unclear. The present study aims to elucidate the protective role of ethanol extract of C. quadrangularis (CQE) including its constituents, quercetin and resveratrol, on hydrogen peroxide (H(2)O(2))-injured human umbilical vein endothelial ECV304 cells. Viability, genotoxicity and protein expression of ECV304 cells were analyzed by MTT, alkaline comet and Western blot, respectively. Production of intracellular reactive oxygen species (ROS) was determined using dichlorofluorescein fluorescence dye. After exposing cells to CQE containing quercetin and resveratrol, DNA damage was not observed. CQE including quercetin and resveratrol significantly attenuated ROS in H(2)O(2)-injured ECV304 cells in a concentration-dependent manner. The protein expression of superoxide dismutase (Cu/Zn-SOD, Mn-SOD), glutathione peroxidase (GPx) and endothelial nitric oxide synthase (eNOS) increased in the cells treated with CQE, quercetin or resveratrol prior to H(2)O(2) exposure, as compared with control. The results provide a molecular mechanism of C. quadrangularis, which could be partially related to quercetin and resveratrol, in restoring ROS in endothelial cells through the upregulation of Cu/Zn-SOD, Mn-SOD, GPx and eNOS. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Caloric restriction improves endothelial dysfunction during vascular aging: Effects on nitric oxide synthase isoforms and oxidative stress in rat aorta.

PubMed

Zanetti, Michela; Gortan Cappellari, Gianluca; Burekovic, Ismet; Barazzoni, Rocco; Stebel, Marco; Guarnieri, Gianfranco

2010-11-01

Aging is characterized by activation of inducible over endothelial nitric oxide synthase (iNOS and eNOS), impaired antioxidant activity and increased oxidative stress, which reduces nitric oxide bioavailability and causes endothelial dysfunction. Caloric restriction (CR) blunts oxidative stress. We investigated whether CR impacts endothelial dysfunction in aging and the underlying mechanisms. Aortas from young (YC, 6 months of age) and old (OC, 24 months of age) rats ad-libitum fed and from old rats caloric-restricted for 3-weeks (OR, 26%) were investigated. Endothelium-dependent vasorelaxation was impaired in OC, associated with reduced eNOS and increased iNOS expression (P<0.05). Aortic nitrite was similar in OC and YC, but the contribution of calcium-independent NOS to total NOS activity was increased whereas that of calcium-dependent NOS was reduced (p≤0.0003). Plasma thiobarbituric acid-reactive substances (TBARS) were elevated in OC as well as aortic nitrotyrosine (P<0.05). Expression of manganese superoxide dismutase (MnSOD) and total SOD activity were impaired in OC (P<0.05 vs. YC), whereas copper-zinc (CuZn) SOD expression was similar in OC and YC. CR restored endothelial dysfunction in old rats, reduced iNOS expression, total nitrite and calcium-independent NOS activity in aorta (P<0.05) without changes in eNOS expression and calcium-dependent NOS activity. Sirtuin-1 expression did not differ among groups. Plasma TBARS and aortic nitrotyrosine were reduced (P<0.05) in OR compared with OC. In OR CuZnSOD protein and SOD activity increased (P<0.05) without changes in MnSOD expression. Short-term CR improves age-related endothelial dysfunction. Reversal of altered iNOS/eNOS ratio, reduced oxidative stress and increased SOD enzyme activity rather than enhanced NO production appear to be involved in this effect. Copyright © 2010 Elsevier Inc. All rights reserved.

Antioxidant genes of the emerald ash borer (Agrilus planipennis): gene characterization and expression profiles.

PubMed

Rajarapu, Swapna Priya; Mamidala, Praveen; Herms, Daniel A; Bonello, Pierluigi; Mittapalli, Omprakash

2011-06-01

Phytophagous insects frequently encounter reactive oxygen species (ROS) from exogenous and endogenous sources. To overcome the effect of ROS, insects have evolved a suite of antioxidant defense genes such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione peroxidase (GPX). The emerald ash borer (Agrilus planipennis Fairmaire), an exotic invasive insect pest from Asia has killed millions of ash trees and continues to invade North America at a rapid pace. From an on-going expressed sequence tag (EST) project of A. planipennis larval tissues, we identified ESTs coding for a Cu-Zn SOD (ApSOD1), a CAT (ApCAT1) and a GPX (ApGPX1). A multiple sequence alignment of the derived A. planipennis sequences revealed high homology with other insect sequences at the amino acid level. Phylogenetic analysis of ApSOD1 grouped it with Cu-Zn SODs of other insect taxa. Quantitative real time PCR (qRT-PCR) analysis in different larval tissues (midgut, fat body, Malpighian tubule and cuticle) revealed high mRNA levels of ApCAT1 in the midgut. Interestingly, high mRNA levels for both ApSOD1 and ApGPX1 were observed in the Malpighian tubules. Assay of mRNA levels in developmental stages (larva, prepupa and adults) by qRT-PCR indicated high transcript levels of ApCAT1 and ApGPX1 in larval and prepupal stages with a decline in adults. On the other hand, the transcript levels of ApSOD1 were observed to be constitutive in all the developmental stages assayed. Results obtained reflect a plausible role of these A. planipennis antioxidant genes in quenching ROS from both diet (ash allelochemicals) as well as endogenous sources. These studies further help in understanding the adaptation/invasiveness of A. planipennis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of pyrogallol, hydroquinone and duroquinone on responses to nitrergic nerve stimulation and NO in the rat anococcygeus muscle

PubMed Central

La, Mylinh; Rand, Michael J

1999-01-01

The hypothesis that endogenous superoxide dismutase (SOD) protects the nitrergic transmitter from inactivation by superoxide and that this explains the lack of sensitivity of the transmitter to superoxide generators was tested in the rat isolated anococcygeus muscle.Responses to nitrergic nerve stimulation or to NO were not significantly affected by exogenous SOD or by the Cu/Zn SOD inhibitor diethyldithiocarbamic acid (DETCA).Hydroquinone produced a concentration-dependent reduction of responses to NO with an IC50 of 27 μM, and higher concentrations reduced relaxant responses to nitrergic nerve stimulation with an IC50 of 612 μM. The effects of hydroquinone were only slightly reversed by SOD, so it does not appear to be acting as a superoxide generator.Pyrogallol produced a concentration-dependent reduction in responses to NO with an IC50 value of 39 μM and this effect was reversed by SOD (100–1000 u ml−1). Pyrogallol did not affect responses to nitrergic nerve stimulation. Treatment with DETCA did not alter the differentiating action of pyrogallol.Duroquinone produced a concentration-dependent reduction of relaxations to NO with an IC50 value of 240 μM and 100 μM slightly decreased nitrergic relaxations. After treatment with DETCA, duroquinone produced greater reductions of relaxant responses to NO and to nitrergic stimulation, the IC50 values being 8.5 μM for NO and 40 μM for nitrergic nerve stimulation: these reductions were reversed by SOD.The findings do not support the hypothesis that the presence of Cu/Zn SOD explains the greater susceptibility of NO than the nitrergic transmitter to the superoxide generator pyrogallol, but suggest that it may play a role in the effects of duroquinone. PMID:10051154

Effect of dietary manganese on antioxidant status and expressions of heat shock proteins and factors in tissues of laying broiler breeders under normal and high environmental temperatures.

PubMed

Zhu, Yong-Wen; Lu, Lin; Li, Wen-Xiang; Zhang, Li-Yang; Ji, Cheng; Lin, Xi; Liu, Hsiao-Ching; Odle, Jack; Luo, Xu-Gang

2016-12-01

To investigate the effect of Mn on antioxidant status and on the expressions of heat shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21±1°C, and high, 32±1°C)×3 dietary Mn treatments (a Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet, either as inorganic Mn sulphate (iMn) or as organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in any of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease Cu Zn superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased Mn superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase in malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expressions of heat shock factor 1 (HSF1) and HSF3 mRNA and heat shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels compared with those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70, HSF1 and HSF3 expressions in the tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance the heart's antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.

Overexpression of CCS in G93A-SOD1 mice leads to accelerated neurological deficits with severe mitochondrial pathology.

PubMed

Son, Marjatta; Puttaparthi, Krishna; Kawamata, Hibiki; Rajendran, Bhagya; Boyer, Philip J; Manfredi, Giovanni; Elliott, Jeffrey L

2007-04-03

Cu, Zn superoxide dismutase (SOD1) has been detected within spinal cord mitochondria of mutant SOD1 transgenic mice, a model of familial ALS. The copper chaperone for SOD1 (CCS) provides SOD1 with copper, facilitates the conversion of immature apo-SOD1 to a mature holoform, and influences in yeast the cytosolic/mitochondrial partitioning of SOD1. To determine how CCS affects G93A-SOD1-induced disease, we generated transgenic mice overexpressing CCS and crossed them to G93A-SOD1 or wild-type SOD1 transgenic mice. Both CCS transgenic mice and CCS/wild-type-SOD1 dual transgenic mice are neurologically normal. In contrast, CCS/G93A-SOD1 dual transgenic mice develop accelerated neurological deficits, with a mean survival of 36 days, compared with 242 days for G93A-SOD1 mice. Immuno-EM and subcellular fractionation studies on the spinal cord show that G93A-SOD1 is enriched within mitochondria in the presence of CCS overexpression. Our results indicate that CCS overexpression in G93A-SOD1 mice produces severe mitochondrial pathology and accelerates disease course.

Age-related differences of semen quality, seminal plasma, and spermatozoa antioxidative and oxidative stress variables in bulls during cold and warm periods of the year.

PubMed

Vince, S; Žura Žaja, I; Samardžija, M; Majić Balić, I; Vilić, M; Đuričić, D; Valpotić, H; Marković, F; Milinković-Tur, S

2018-03-01

The aims of this study were to determine the presence and quantities of antioxidative status and oxidative stress (OS) variables in the seminal plasma and spermatozoa of bulls of varying age during cold and warm periods of the year, and to establish the correlation of these variables with semen quality parameters. The study was conducted on two groups each comprising nine Simmental bulls: one group contained younger animals (aged 2 to 4 years) and the second older animals (aged 5 to 10 years). Semen samples were collected using an artificial vagina for biochemical analysis. Seminal plasma and spermatozoa activities of total superoxide dismutase (TSOD), manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), selenium-dependent glutathione peroxidase, reduced glutathione and concentrations of total protein (TP), thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) were determined. Several antioxidants in seminal plasma were also determined: total glutathione peroxidase (TGSH-Px), selenium-independent glutathione peroxidase (Non-SeGSH-Px), uric acid, albumins (ALB) and alkaline phosphatase (ALP). Significantly higher spermatozoa motility was observed during the cold v. warm period, and a significantly higher volume and total number of spermatozoa per ejaculate was observed in older than in younger bulls. Significantly higher values of ALP, TP and ALB were found in seminal plasma of older bulls than in younger bulls during the warm period. The seminal plasma of younger bulls showed significantly higher activities of TSOD, MnSOD, CuZnSOD, TGSH-Px and Non-SeGSH-Px. Younger bulls had significantly higher PCC concentration and activity of CAT in seminal plasma than older bulls during the cold period. Significantly higher concentrations of PCC and TBARS, and activities of TSOD, MnSOD and CuZnSOD were established in spermatozoa of the younger than in older bulls during the warm period. It could be concluded that antioxidative and OS variables differ significantly depending on bull age and time of year. Younger bulls were more sensitive to elevated ambient temperatures during the warm period, when the higher enzymatic antioxidative protection in seminal plasma and spermatozoa were insufficient to counteract the intensive oxidative processes in spermatozoa, which eventually resulted in decreased spermatozoa motility. The estimation of antioxidative and OS variables in seminal plasma and spermatozoa may have practical value for the assessment of bull semen quality.

Methane alleviates copper-induced seed germination inhibition and oxidative stress in Medicago sativa.

PubMed

Samma, Muhammad Kaleem; Zhou, Heng; Cui, Weiti; Zhu, Kaikai; Zhang, Jing; Shen, Wenbiao

2017-02-01

Recent results discovered the protective roles of methane (CH 4 ) against oxidative stress in animals. However, the possible physiological roles of CH 4 in plants are still unknown. By using physiological, histochemical and molecular approaches, the beneficial role of CH 4 in germinating alfalfa seeds upon copper (Cu) stress was evaluated. Endogenous production of CH 4 was significantly increased in Cu-stressed alfalfa seeds, which was mimicked by 0.39 mM CH 4 . The pretreatment with CH 4 significantly alleviated the inhibition of seed germination and seedling growth induced by Cu stress. Cu accumulation was obviously blocked as well. Meanwhile, α/β amylase activities and sugar contents were increased, all of which were consistent with the alleviation of seed germination inhibition triggered by CH 4 . The Cu-triggered oxidative stress was also mitigated, which was confirmed by the decrease of lipid peroxidation and reduction of Cu-induced loss of plasma membrane integrity in CH 4 -pretreated alfalfa seedlings. The results of antioxidant enzymes, including ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (POD) total or isozymatic activities, and corresponding transcripts (APX1/2, Cu/Zn SOD and Mn-SOD), indicated that CH 4 reestablished cellular redox homeostasis. Further, Cu-induced proline accumulation was partly impaired by CH 4 , which was supported by the alternation of proline metabolism. Together, these results indicated that CH 4 performs an advantageous effect on the alleviation of seed germination inhibition caused by Cu stress, and reestablishment of redox homeostasis mainly via increasing antioxidant defence.

Concurrent Increases and Decreases in Local Stability and Conformational Heterogeneity in Cu, Zn Superoxide Dismutase Variants Revealed by Temperature-Dependence of Amide Chemical Shifts.

PubMed

Doyle, Colleen M; Rumfeldt, Jessica A; Broom, Helen R; Sekhar, Ashok; Kay, Lewis E; Meiering, Elizabeth M

2016-03-08

The chemical shifts of backbone amide protons in proteins are sensitive reporters of local structural stability and conformational heterogeneity, which can be determined from their readily measured linear and nonlinear temperature-dependences, respectively. Here we report analyses of amide proton temperature-dependences for native dimeric Cu, Zn superoxide dismutase (holo pWT SOD1) and structurally diverse mutant SOD1s associated with amyotrophic lateral sclerosis (ALS). Holo pWT SOD1 loses structure with temperature first at its periphery and, while having extremely high global stability, nevertheless exhibits extensive conformational heterogeneity, with ∼1 in 5 residues showing evidence for population of low energy alternative states. The holo G93A and E100G ALS mutants have moderately decreased global stability, whereas V148I is slightly stabilized. Comparison of the holo mutants as well as the marginally stable immature monomeric unmetalated and disulfide-reduced (apo(2SH)) pWT with holo pWT shows that changes in the local structural stability of individual amides vary greatly, with average changes corresponding to differences in global protein stability measured by differential scanning calorimetry. Mutants also exhibit altered conformational heterogeneity compared to pWT. Strikingly, substantial increases as well as decreases in local stability and conformational heterogeneity occur, in particular upon maturation and for G93A. Thus, the temperature-dependence of amide shifts for SOD1 variants is a rich source of information on the location and extent of perturbation of structure upon covalent changes and ligand binding. The implications for potential mechanisms of toxic misfolding of SOD1 in disease and for general aspects of protein energetics, including entropy-enthalpy compensation, are discussed.

Copper Homeostasis as a Therapeutic Target in Amyotrophic Lateral Sclerosis with SOD1 Mutations

PubMed Central

Tokuda, Eiichi; Furukawa, Yoshiaki

2016-01-01

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease affecting both upper and lower motor neurons, and currently, there is no cure or effective treatment. Mutations in a gene encoding a ubiquitous antioxidant enzyme, Cu,Zn-superoxide dismutase (SOD1), have been first identified as a cause of familial forms of ALS. It is widely accepted that mutant SOD1 proteins cause the disease through a gain in toxicity but not through a loss of its physiological function. SOD1 is a major copper-binding protein and regulates copper homeostasis in the cell; therefore, a toxicity of mutant SOD1 could arise from the disruption of copper homeostasis. In this review, we will briefly review recent studies implying roles of copper homeostasis in the pathogenesis of SOD1-ALS and highlight the therapeutic interventions focusing on pharmacological as well as genetic regulations of copper homeostasis to modify the pathological process in SOD1-ALS. PMID:27136532

Copper Homeostasis as a Therapeutic Target in Amyotrophic Lateral Sclerosis with SOD1 Mutations.

PubMed

Tokuda, Eiichi; Furukawa, Yoshiaki

2016-04-28

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease affecting both upper and lower motor neurons, and currently, there is no cure or effective treatment. Mutations in a gene encoding a ubiquitous antioxidant enzyme, Cu,Zn-superoxide dismutase (SOD1), have been first identified as a cause of familial forms of ALS. It is widely accepted that mutant SOD1 proteins cause the disease through a gain in toxicity but not through a loss of its physiological function. SOD1 is a major copper-binding protein and regulates copper homeostasis in the cell; therefore, a toxicity of mutant SOD1 could arise from the disruption of copper homeostasis. In this review, we will briefly review recent studies implying roles of copper homeostasis in the pathogenesis of SOD1-ALS and highlight the therapeutic interventions focusing on pharmacological as well as genetic regulations of copper homeostasis to modify the pathological process in SOD1-ALS.

Developmental and environmental regulation of the Nicotiana plumbaginifolia cytosolic Cu/Zn-superoxide dismutase promoter in transgenic tobacco.

PubMed Central

Hérouart, D; Van Montagu, M; Inzé, D

1994-01-01

Superoxide dismutases (SODs) play a key role in the cellular defense against reactive oxygen species. To study the transcriptional regulation at the cellular level, the promoter of the Nicotiana plumbaginifolia cytosolic gene encoding Cu/ZnSOD (SODCc) was fused to the beta-glucuronidase (GUS) reporter gene (gusA) and analyzed in transgenic tobacco plants. The promoter was highly active in vascular bundles of leaves and stems, where it is confined to phloem cells. In flowers, GUS activity was detected in ovules and pollen grains, in pigmented tissues of petals, and in vascular tissue of ovaries and anthers. In response to treatment with the superoxide-generating herbicide paraquat, very strong GUS staining was observed in photosynthetically active cells of leaves and in some epidermal root cells of seedlings. The expression of the SODCc-gusA was also induced in seedlings after heat shock and chilling and after treatment with sulfhydryl antioxidants such as reduced glutathione and cysteine. It is postulated that SODCc expression is directly linked to a cell-specific production of excess superoxide radicals in the cytosol. PMID:8165260

Developmental and environmental regulation of the Nicotiana plumbaginifolia cytosolic Cu/Zn-superoxide dismutase promoter in transgenic tobacco.

PubMed

Hérouart, D; Van Montagu, M; Inzé, D

1994-03-01

Superoxide dismutases (SODs) play a key role in the cellular defense against reactive oxygen species. To study the transcriptional regulation at the cellular level, the promoter of the Nicotiana plumbaginifolia cytosolic gene encoding Cu/ZnSOD (SODCc) was fused to the beta-glucuronidase (GUS) reporter gene (gusA) and analyzed in transgenic tobacco plants. The promoter was highly active in vascular bundles of leaves and stems, where it is confined to phloem cells. In flowers, GUS activity was detected in ovules and pollen grains, in pigmented tissues of petals, and in vascular tissue of ovaries and anthers. In response to treatment with the superoxide-generating herbicide paraquat, very strong GUS staining was observed in photosynthetically active cells of leaves and in some epidermal root cells of seedlings. The expression of the SODCc-gusA was also induced in seedlings after heat shock and chilling and after treatment with sulfhydryl antioxidants such as reduced glutathione and cysteine. It is postulated that SODCc expression is directly linked to a cell-specific production of excess superoxide radicals in the cytosol.

Trace elements and antioxidant enzymes in Behçet's disease.

PubMed

Saglam, K; Serce, A F; Yilmaz, M I; Bulucu, F; Aydin, A; Akay, C; Sayal, A

2002-07-01

Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of Behçet's disease (BD). Trace elements function as cofactors to antioxidant enzymes. The antioxidant system and trace elements were investigated in many different studies, including BD, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in BD to contribute to the knowledge of pathogenesis and treatment of this disease. We examined glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities together with selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels in plasma and erythrocytes of 50 patients with BD and 30 healthy controls. It was found that in patients with BD, erythrocyte GSH-Px and SOD activities and erythrocyte Se, plasma Fe, Mn, and Zn levels were significantly lower than those of controls and that plasma Cu, erythrocyte Zn, and Mn levels were significantly higher in patients with BD. Insufficient antioxidant enzyme activities were observed in patients with BD. The mechanism(s) of this phenomenon is not clear. Therefore, supplementation with trace elements involved in the antioxidative processes may increase scavenger enzyme activities, and consequently, an improvement in clinical symptoms may be expected.

Short-term effects of sibutramine on mineral status and selected biochemical parameters in obese women.

PubMed

Suliburska, Joanna; Bogdański, Paweł; Szulińska, Monika; Pupek-Musialik, Danuta

2012-11-01

The aim of this study was to assess the effect of sibutramine on mineral status and selected biochemical parameters in obese women. The study was conducted on 24 patients who received 15 mg daily doses of sibutramine for 12 weeks, and on 20 patients who received placebo. At the baseline, after the sixth and twelfth weeks of treatment, body weight and blood pressure were measured, the BMI was calculated, and samples of blood and of first morning urine were collected. Serum lipid profiles, glucose levels, and nitric oxide levels were determined. The iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), and magnesium (Mg) present in the serum and urine samples were assessed. The erythrocyte hemolysate of the patients was use to assay the activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). No changes were observed in BMI, blood pressure, or nitric oxide during the study. After 12 weeks of treatment, a decrease was observed in total cholesterol, LDL cholesterol, triglyceride, glucose, and ferritin levels. GSH-Px and SOD activity increased after 12 weeks of sibutramine treatment. The Mg and Cu increases was observed in serum after the sixth and twelfth weeks of treatment. It was found that the Zn level decreased in serum after the twelfth week. The elimination of Ca, Mg, Fe, Zn, and Cu in urine also declined in the twelfth week. No differences were found in the women taking the placebo. In conclusion, we found that sibutramine had a positive effect on lipid and glucose status in obese women. However, the drug disturbed the balance of minerals, especially Zn and Mg, in the subjects.

Compartmentalized oxidative stress in dopaminergic cell death induced by pesticides and complex I inhibitors: Distinct roles of superoxide anion and superoxide dismutases

PubMed Central

Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely; Pickett, Chillian; Sumin, Li; Jones, Jocelyn; Chen, Han; Webb, Brian; Choi, Jae; Zhou, You; Zimmerman, Matthew C.; Franco, Rodrigo

2013-01-01

The loss of dopaminergic neurons induced by the parkinsonian toxins paraquat, rotenone and 1-methyl-4-phenylpyridinium (MPP+) is associated with oxidative stress. However, controversial reports exist regarding the source/compartmentalization of reactive oxygen species (ROS) generation and its exact role in cell death. We aimed to determine in detail the role of superoxide anion (O2•−), oxidative stress and their subcellular compartmentalization in dopaminergic cell death induced by parkinsonian toxins. Oxidative stress and ROS formation was determined in the cytosol, intermembrane (IMS) and mitochondrial matrix compartments, using dihydroethidine derivatives, the redox sensor roGFP, as well as electron paramagnetic resonance spectroscopy. Paraquat induced an increase in ROS and oxidative stress in both the cytosol and mitochondrial matrix prior to cell death. MPP+ and rotenone primarily induced an increase in ROS and oxidative stress in the mitochondrial matrix. No oxidative stress was detected at the level of the IMS. In contrast to previous studies, overexpression of manganese superoxide dismutase (MnSOD) or copper/zinc SOD (CuZnSOD) had no effect on ROS steady state levels, lipid peroxidation, loss of mitochondrial membrane potential (ΔΨm) and dopaminergic cell death induced by MPP+ or rotenone. In contrast, paraquat-induced oxidative stress and cell death were selectively reduced by MnSOD overexpression, but not by CuZnSOD or manganese-porphyrins. However, MnSOD also failed to prevent ΔΨm loss. Finally, paraquat, but not MPP+ or rotenone, induced the transcriptional activation the redox-sensitive antioxidant response elements (ARE) and nuclear factor kappa-B (NF-κB). These results demonstrate a selective role of mitochondrial O2•− in dopaminergic cell death induced by paraquat, and show that toxicity induced by the complex I inhibitors rotenone and MPP+ does not depend directly on mitochondrial O2•− formation. PMID:23602909

Transcriptional analysis of disk abalone (Haliotis discus discus) antioxidant enzymes against marine bacteria and virus challenge.

PubMed

De Zoysa, Mahanama; Whang, Ilson; Nikapitiya, Chamilani; Oh, Chulhong; Choi, Cheol Young; Lee, Jehee

2011-07-01

Diverse antioxidant enzymes are essential for marine organisms to overcome oxidative stress as well as for the fine-tuning of immune reactions through activating different signal transduction pathways. This study describes the transcriptional analysis of antioxidant enzymes of disk abalone by challenging with bacteria (Vibrio alginolyticus, Vibrio parahemolyticus, and Listeria monocytogenes) and viral hemorrhagic septicemia virus (VHSV). Upon bacteria and VHSV challenge, Manganese superoxide dismutase (MnSOD), Copper, Zinc superoxide dismutase (CuZnSOD), catalase, thioredoxin peroxidase (TPx), Selenium-dependent glutathione peroxidase (SeGPx), and thioredoxin-2 (TRx-2) expression levels were altered in gills, and hemocytes at different magnitudes. In gills, only MnSOD, catalase, and SeGPx genes were completely upregulated by post-challenge of bacterial and VHSV. Among them, SeGPx demonstrated strong upregulation by 16-fold (bacteria) and 2-fold (VHSV) in gills, and 5-fold (bacteria) and 3.0-fold (VHSV) in hemocytes. None of the genes examined were downregulated (in gills and hemocytes) by bacteria challenge even though CuZnSOD and TPx showed downregulation (completely) in hemocytes by VHSV. In general, abalone hemocytes had lower potential to induce antioxidant enzyme transcripts upon bacteria and VHSV challenge than gills. Based upon these results, we suggest that abalones induce oxidative stress in tissues during the bacteria and VHSV challenge, and the identified response of antioxidant enzymes could be supported for maintaining a low-level of reactive oxygen species (ROS) that may serve as a signal for activating immune reactions against pathogenic conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genome-Wide Identification and Transcriptional Expression Analysis of Cucumber Superoxide Dismutase (SOD) Family in Response to Various Abiotic Stresses

PubMed Central

Zhou, Yong; Hu, Lifang; Wu, Hao; Jiang, Lunwei

2017-01-01

Superoxide dismutase (SOD) proteins are widely present in the plant kingdom and play important roles in different biological processes. However, little is known about the SOD genes in cucumber. In this study, night SOD genes were identified from cucumber (Cucumis sativus) using bioinformatics-based methods, including 5 Cu/ZnSODs, 3 FeSODs, and 1 MnSOD. Gene structure and motif analysis indicated that most of the SOD genes have relatively conserved exon/intron arrangement and motif composition. Phylogenetic analyses with SODs from cucumber and several other species revealed that these SOD proteins can be traced back to two ancestral SODs before the divergence of monocot and dicot plants. Many cis-elements related to stress responses and plant hormones were found in the promoter sequence of each CsSOD gene. Gene expression analysis revealed that most of the CsSOD genes are expressed in almost all the tested tissues. qRT-PCR analysis of 8 selected CsSOD genes showed that these genes could respond to heat, cold, osmotic, and salt stresses. Our results provide a basis for further functional research on SOD gene family in cucumber and facilitate their potential applications in the genetic improvement of cucumber. PMID:28808654

Anti-cancer efficacy of nonthermal plasma dissolved in a liquid, liquid plasma in heterogeneous cancer cells

NASA Astrophysics Data System (ADS)

Nguyen, Ngoc Hoan; Park, Hyung Jun; Yang, Sang Sik; Choi, Kyeong Sook; Lee, Jong-Soo

2016-07-01

The therapeutic potential of nonthermal plasma for cancer treatment has been reported recently. The heterogeneity of cancer cells need to be addressed to design effective anticancer treatments. Here, we show that treatment with nonthermal atmospheric-pressure plasma dissolved in a liquid (liquid plasma) induces oxidative stress in heterogeneous populations of cancer cells and ultimately kills these cells via apoptosis, regardless of genetic status, e.g., mutations in p53 and other DNA-damage-response genes. We found that liquid plasma markedly increased the concentration of intracellular and mitochondrial reactive oxygen species (ROS), reflecting an influx from the extracellular milieu. Liquid plasma contributed to mitochondrial accumulation of ROS and depolarization of mitochondrial membrane potential with consequent cell death. Healthy normal cells, however, were hardly affected by the liquid-plasma treatment. The antioxidant N-acetylcysteine blocked liquid-plasma-induced cell death. A knockdown of CuZn-superoxide dismutase or Mn-SOD enhanced the plasma-induced cell death, whereas expression of exogenous CuZn-SOD, Mn-SOD, or catalase blocked the cell death. These results suggest that the mitochondrial dysfunction mediated by ROS production is a key contributor to liquid-plasma-induced apoptotic cell death, regardless of genetic variation. Thus, liquid plasma may have clinical applications, e.g., the development of therapeutic strategies and prevention of disease progression despite tumor heterogeneity.

Metal-deficient SOD1 in amyotrophic lateral sclerosis.

PubMed

Hilton, James B; White, Anthony R; Crouch, Peter J

2015-05-01

Mutations to the ubiquitous antioxidant enzyme Cu/Zn superoxide dismutase (SOD1) were the first established genetic cause of the fatal, adult-onset neurodegenerative disease amyotrophic lateral sclerosis (ALS). It is widely accepted that these mutations do not cause ALS via a loss of antioxidant function, but elucidating the alternate toxic gain of function has proven to be elusive. Under physiological conditions, SOD1 binds one copper ion and one zinc ion per monomer to form a highly stable and functional homodimer, but there is now ample evidence to indicate aberrant persistence of SOD1 in an intermediate metal-deficient state may contribute to the protein's involvement in ALS. This review briefly discusses some of the data to support a role for metal-deficient SOD1 in the development of ALS and some of the outcomes from drug development studies that have aimed to modify the symptoms of ALS by targeting the metal state of SOD1. The implications for the metal state of SOD1 in cases of sporadic ALS that do not involve mutant SOD1 are also discussed.

Effects of Edaravone on Hippocampal Antioxidants in EL Mice.

PubMed

Baba, Asami; Kawakami, Yasuhiko; Saito, Kenichi; Murashima, Yoshiya L; Itoh, Yasuhiko

2016-01-01

The role of oxidative stress in susceptibility to seizures has been the focus of several recent studies. The aim of the present study was to evaluate the antiepileptic effects of the free radical scavenger edaravone on EL mice, a strain that is highly susceptible to convulsive seizures. EL mice were treated intraperitoneally with edaravone or saline for 1 week. The levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and 3 isozymes of superoxide dismutase (SOD) (cytoplasmic copper- and zinc-containing SOD, extracellular SOD, and mitochondrial manganese-containing SOD) were measured in the hippocampus, and electroencephalograms (EEGs) were used to evaluate seizure sensitivity. Hippocampal levels of GSSG were lower in the edaravone group than in the untreated control group, and the GSH/GSSG ratio, Cu/Zn-SOD, and EC-SOD activities were higher in the edaravone group. Edaravone shortened the duration of interictal spike discharges and clinically suppressed epileptic seizures. Edaravone increases antioxidant potency and reduces seizure susceptibility in EL mice, making it a promising novel antiepileptic agent.

CuInS2/ZnS QD exposure induces developmental toxicity, oxidative stress and DNA damage in rare minnow (Gobiocypris rarus) embryos and larvae.

PubMed

Liu, Li; Xiao, Yuan-Yuan; Ji, Yan-Hong; Liu, Ming-Zhi; Chen, Yao; Zeng, Yu-Lian; Zhang, Yao-Guang; Jin, Li

2017-08-01

Chinese rare minnow (Gobiocypris rarus) embryos were used as an experimental model to investigate the effects of CuInS 2 /ZnS quantum dots (QDs) on the early life stages of G. rarus. Normal developmental parameters (survival rate, body length and average heart rate), biomarker genes [stress response (Hsp70), detoxification (Cyp1a), organizer function and axis formation (Wnt8α), and muscle (Mstn)], enzymatic activity and DNA damage were recorded as endpoints in the developing embryos/larvae after exposure until 96h post-fertilization (hpf). Reduced survival rate, decreased heart rate, altered body length, increased malformation rate, decreased hatching rate, advanced hatching time in response to low concentrations (50 and 100nmol/L) and delayed hatching time in response to high concentrations were observed after exposure, as were many other toxic effects, including pericardial edema and bent tails. The 72 hpf LC 50 (median lethal concentration) was determined to be 624.364nmol/L. Treatment with certain concentrations of CuInS 2 /ZnS QDs significantly increased the superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels and significantly induced DNA damage. After treatment with CuInS 2 /ZnS QDs, the embryos showed highly up-regulated expression of Hsp70, Cyp1a and Wnt8a and significantly up-regulated expression of Mstn at 12 hpf. Overall, this study indicates that CuInS 2 /ZnS QDs are potentially toxic to G. rarus embryos. The information presented in this study will be helpful for fully understanding the toxicity induced by CuInS 2 /ZnS QDs in fish embryos. Copyright © 2017 Elsevier Inc. All rights reserved.

Parkin Protects Against Misfolded SOD1 Toxicity by Promoting Its Aggresome Formation and Autophagic Clearance.

PubMed

Yung, Cheryl; Sha, Di; Li, Lian; Chin, Lih-Shen

2016-11-01

Mutations in Cu/Zn superoxide dismutase (SOD1) cause autosomal dominant amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease with no effective treatment. Despite ample evidence indicating involvement of mutation-induced SOD1 protein misfolding and aggregation in ALS pathogenesis, the molecular mechanisms that control cellular management of misfolded, aggregation-prone SOD1 mutant proteins remain unclear. Here, we report that parkin, an E3 ubiquitin-protein ligase which is linked to Parkinson's disease, is a novel regulator of cellular defense against toxicity induced by ALS-associated SOD1 mutant proteins. We find that parkin mediates K63-linked polyubiquitination of SOD1 mutants in cooperation with the UbcH13/Uev1a E2 enzyme and promotes degradation of these misfolded SOD1 proteins by the autophagy-lysosome system. In response to strong proteotoxic stress associated with proteasome impairment, parkin promotes sequestration of misfolded and aggregated SOD1 proteins to form perinuclear aggresomes, regulates positioning of lysosomes around misfolded SOD1 aggresomes, and facilitates aggresome clearance by autophagy. Our findings reveal parkin-mediated cytoprotective mechanisms against misfolded SOD1 toxicity and suggest that enhancing parkin-mediated cytoprotection may provide a novel therapeutic strategy for treating ALS.

Can ebselen prevent cisplatin-induced ovarian damage?

PubMed

Soyman, Zeynep; Uzun, Hafize; Bayindir, Nihan; Esrefoglu, Mukaddes; Boran, Birtan

2018-06-01

The occurrence of ovarian damage is a major shortcoming in treating tumors with cisplatin (CP). The present study investigates the beneficial effects of ebselen-a seleno-organic compound with antioxidant and antiinflammatory properties-vis-à-vis CP-induced ovarian damage. Twenty-eight adult female rats were divided into four study groups. Group 1 received no treatment. The rats in Groups 2, 3, and 4 were intraperitoneally administered CP (2 mg/kg/day) twice per week, for 5 weeks. Those in Group 2 received 0.3 ml saline (0.9% NaCl) intraperitoneally 60 min before each CP treatment, while those in Group 3 received 0.2 ml dimethyl sulfoxide (DMSO) and 0.3 ml saline intraperitoneally 60 min before each CP treatment. The rats in Group 4 were pretreated with an intraperitoneal injection of 15 mg/kg/day ebselen 60 min before each CP treatment. Ovarian tissue malondialdehyde (MDA), total nitric oxide (NOx), glutathione (GSH), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and catalase levels, as well as histopathological damage scores (HDSs) and serum antimullerian hormone (AMH) levels, were assessed. Cu/Zn-SOD and GSH levels were significantly higher, and MDA and NOx levels significantly lower, in Group 4 than in Groups 2 and 3. Pretreatment with ebselen significantly improved serum AMH levels, relative to Groups 2 and 3. Additionally, HDS values were significantly lower in Group 4 than in Groups 2 and 3. Our results from using an experimental rat model of CP chemotherapy suggest that ebselen use may ameliorate ovarian damage by preventing oxidative injury.

Copper/Zinc-Superoxide Dismutase Is Required for Oxytetracycline Resistance of Saccharomyces cerevisiae

PubMed Central

Avery, Simon V.; Malkapuram, Srividya; Mateus, Carolina; Babb, Kimberly S.

2000-01-01

Saccharomyces cerevisiae, along with other eukaryotes, is resistant to tetracyclines. We found that deletion of SOD1 (encoding Cu/Zn superoxide dismutase) rendered S. cerevisiae hypersensitive to oxytetracycline (OTC): a sod1Δ mutant exhibited a >95% reduction in colony-forming ability at an OTC concentration of 20 μg ml−1, whereas concentrations of up to 1,000 μg ml−1 had no effect on the growth of the wild type. OTC resistance was restored in the sod1Δ mutant by complementation with wild-type SOD1. The effect of OTC appeared to be cytotoxic and was not evident in a ctt1Δ (cytosolic catalase) mutant or in the presence of tetracycline. SOD1 transcription was not induced by OTC, suggesting that constitutive SOD1 expression is sufficient for wild-type OTC resistance. OTC uptake levels in wild-type and sod1Δ strains were similar. However, lipid peroxidation and protein oxidation were both enhanced during exposure of the sod1Δ mutant, but not the wild type, to OTC. We propose that Sod1p protects S. cerevisiae against a mode of OTC action that is dependent on oxidative damage. PMID:10613865

Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1.

PubMed

Ghadge, Ghanashyam D; Pavlovic, John D; Koduvayur, Sujatha P; Kay, Brian K; Roos, Raymond P

2013-08-01

Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as 'intrabodies' within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity. Copyright © 2013 Elsevier Inc. All rights reserved.

Phytotoxicity of carbon nanotubes in soybean as determined by interactions with micronutrients

NASA Astrophysics Data System (ADS)

Zaytseva, Olga; Wang, Zhengrui; Neumann, Günter

2017-02-01

Carbon nanomaterials released into the environment exert extremely variable effects on living organisms. In this study, we used soybean ( Glycine max) to investigate early responses to seed exposure to multi-walled carbon nanotubes (MWCNTs, outer diameter 20-70 nm, inner diameter 5-10 nm, length of >2 μm). Soybean seeds were imbibed with deionised water (control) or MWCNT suspension (1000 mg L-1) and were analysed for MWCNT contamination using light microscopy. The seedlings vitality status was evaluated by staining with triphenyltetrazolium chloride and measurement of oxidative stress indicators in the root tissue. Micronutrient (Zn, Mn, Cu) availability in different seedling organs was assessed and the effects of antioxidants, and micronutrient supplementation was investigated. Oxidative stress induction by MWCNTs was detectable in radicle tips, coincided with MWCNTs accumulation and was reverted by external application of proline as antioxidant and micronutrients (Zn, Cu, Mn) as cofactors for various enzymes involved in oxidative stress defence. Accordingly, SOD activity increased after Zn supplementation. During germination, the MWCNT treatments reduced Zn translocation from the cotyledons to the seedling and MWCNTs exhibited adsorption potential for Zn and Cu, which may be involved in internal micronutrients immobilisation. This study demonstrates for the first time that MWCNT phytotoxicity is linked with oxidative stress-related disturbances of micronutrient homeostasis.

Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

PubMed

Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

2009-08-01

The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

Effects of a flavonoid extract from Cynomorium songaricum on the swimming endurance of rats.

PubMed

Yu, Fa-Rong; Liu, Ying; Cui, Yong-Zhi; Chan, Er-Qing; Xie, Ming-Ren; McGuire, Peter P; Yu, Fa-Hong

2010-01-01

The present study investigated the effects of a flavonoid extract from Cynomorium songaricum on the swimming endurance of rats by measuring changes of free radical scavenging enzymes, such as CuZn-SOD (copper, zinc-superoxide dismutase) and GSH-px (glutathione peroxidase), and body weights. Significant and dose-dependent antioxidant and anti-fatigue effects of flavonoids (rutin, catechin and isoquercitrin) on swimming rats were observed during 10 days of swimming exercise. After treatment with the flavonoid extract at doses of 0.5, 1.0, and 2.0 g/kg body weight, the CuZn-SOD and GSH-px activities in swimming rats were increased by 1.4%, 3.3%, 4.1% and 112.2%, 208.7%, 261.7%, respectively, while the levels of MDA (malondialdehyde) were decreased by 64.7%, 79.4%, and 86.4% respectively. Furthermore, the average body weight and the total swimming time were increased by 3.1%, 8.8%, 10.6%, and 7.7%, 34.5%, 61.5%, respectively. Our experimental results suggest that flavonoid supplementation could not only reduce free radical formation and scavenge free radicals, but also enhance endurance exercise performance by reducing muscle fatigue.

Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo.

PubMed

Wang, Jun-ming; Sheng, Yu-chen; Ji, Li-li; Wang, Zheng-tao

2014-06-01

The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity.

Differences in seminal plasma and spermatozoa antioxidative systems and seminal plasma lipid and protein levels among boar breeds and hybrid genetic traits.

PubMed

Žura Žaja, Ivona; Samardžija, Marko; Vince, Silvijo; Vilić, Marinko; Majić-Balić, Ivanka; Đuričić, Dražen; Milinković-Tur, Suzana

2016-07-01

The objectives of this study were to determine the influence of breed and hybrid genetic traits of boars on lipid and protein concentrations and antioxidative system variables in seminal plasma (SP) and spermatozoa and their correlations with semen quality variables. Semen samples from 27 boars: Swedish Landraces (SL), German Landraces (GL), Large Whites (LW), Pietrains (P) and Pig Improvement Company hybrids (PIC-hybrid), aged from 1.5 to 3 years old, were collected. SP was spectrophotometrically analyzed to determine total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG), total protein (TP), albumin, and zinc concentrations. The antioxidative system in SP and spermatozoa was established spectrophotometrically by determining total antioxidative status (TAS), total superoxide dismutase (TSOD) and glutathione peroxidase (GSH-Px) parameters, as well as copper-zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activity in spermatozoa. The hybrid boars had higher (P<0.05) SP concentrations of: TC, LDL-C and TAG than P and GL; HDL-C than P, GL and SL; and TP than P and LW. PIC-hybrid had lower values (P<0.05) in spermatozoa of: TAS and CuZnSOD than SL; TSOD and GSH-Px than SL and P; and MnSOD than SL and LW. Differences in SP and spermatozoa antioxidative system variables and the significant differences in SP protein and lipid variables exist among boars of different breeds and hybrid. Novel data and observed differences in semen variables among boar breeds and hybrids and their correlations with semen quality parameters in this study could contribute to better assessment of boar semen quality. Copyright © 2016 Elsevier B.V. All rights reserved.

Protein oxidative damage and heme oxygenase in sunlight-exposed human skin: roles of MAPK responses to oxidative stress.

PubMed

Akasaka, Emiko; Takekoshi, Susumu; Horikoshi, Yosuke; Toriumi, Kentarou; Ikoma, Norihiro; Mabuchi, Tomotaka; Tamiya, Shiho; Matsuyama, Takashi; Ozawa, Akira

2010-12-20

Oxidative stress derived from ultraviolet (UV) light in sunlight induces different hazardous effects in the skin, including sunburn, photo-aging and DNA mutagenesis. In this study, the protein-bound lipid peroxidation products 4-hydroxy-2-nonenal (HNE) and the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8OHdG) were investigated in chronically sun-exposed and sun-protected human skins using immunohistochemistry. The levels of antioxidative enzymes, such as heme oxygenase 1 and 2, Cu/Zn-SOD, Mn-SOD and catalase, were also examined. Oxidative stress is also implicated in the activation of signal transduction pathways, such as mitogen-activated protein kinase (MAPK). Therefore, the expression and distribution of phosphorylated p38 MAPK, phosphorylated Jun N-terminal kinase (JNK) and phosphorylated extracellular signal-regulated kinase (ERK) were observed. Skin specimens were obtained from the surgical margins. Chronically sunlight-exposed skin samples were taken from the ante-auricular (n = 10) and sunlight-protected skin samples were taken from the post-auricular (n = 10). HNE was increased in the chronically sunlight-exposed skin but not in the sunlight-protected skin. The expression of heme oxygenase-2 was markedly increased in the sunlight-exposed skin compared with the sun-protected skin. In contrast, the intensity of immunostaining of Cu/Zn-SOD, Mn-SOD and catalase was not different between the two areas. Phosphorylated p38 MAPK and phosphorylated JNK accumulated in the ante-auricular dermis and epidermis, respectively. These data show that particular anti-oxidative enzymes function as protective factors in chronically sunlight-exposed human skin. Taken together, our results suggest (1) antioxidative effects of heme oxygenase-2 in chronically sunlight-exposed human skin, and that (2) activation of p38 MAPK may be responsible for oxidative stress.

Effect of fraxetin on antioxidant defense and stress proteins in human neuroblastoma cell model of rotenone neurotoxicity. Comparative study with myricetin and N-acetylcysteine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molina-Jimenez, Maria Francisca; Sanchez-Reus, Maria Isabel; Cascales, Maria

2005-12-15

Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. Recently, it has been shown that fraxetin (coumarin) and myricetin (flavonoid) have significant neuroprotective effects against apoptosis induced by rotenone, increase the total glutathione levels in vitro, and inhibit lipid peroxidation. Thus, these considerations prompted us to investigate the way in which fraxetin and myricetin affect the endogenous antioxidant defense system, such as Mn and CuZn superoxide dismutase (MnSOD, CuZnSOD), catalase, glutathione reductase (GR), and glutathione peroxidase (GPx) on rotenone neurotoxicity in neuroblastoma cells. N-acetylcysteine (NAC), a potent antioxidant, was employed as a comparative agent. Also,more » the expression and protein levels of HSP70 by Northern and Western blot analysis were assayed in SH-SY5Y cells. After incubation for 16 h, rotenone significantly increased the expression and activity of MnSOD, GPx, and catalase. When cells were preincubated with fraxetin, there was a decrease in the protein levels and activity of both MnSOD and catalase, in comparison with the rotenone treatment. The myricetin effect was less pronounced. Activity and expression of GPx were increased by rotenone and pre-treatment with fraxetin did not modify significantly these levels. The significant enhancement in HSP70 expression at mRNA and protein levels induced by fraxetin was observed by pre-treatment of cells 0.5 h before rotenone insult. These data suggest that major features of rotenone-induced neurotoxicity are partially mediated by free radical formation and oxidative stress, and that fraxetin partially protects against rotenone toxicity affecting the main protection system of the cells against oxidative injury.« less

Cu,Zn-superoxide dismutase is lower and copper chaperone CCS is higher in erythrocytes of copper-deficient rats and mice.

PubMed

West, Elizabeth C; Prohaska, Joseph R

2004-09-01

Discovery of a sensitive blood biochemical marker of copper status would be valuable for assessing marginal copper intakes. Rodent models were used to investigate whether erythrocyte concentrations of copper,zinc-superoxide dismutase (SOD), and the copper metallochaperone for SOD (CCS) were sensitive to dietary copper changes. Several models of copper deficiency were studied in postweanling male Holtzman rats, male Swiss Webster mice offspring, and both rat and mouse dams. Treatment resulted in variable but significantly altered copper status as evaluated by the presence of anemia, and lower liver copper and higher liver iron concentrations in copper-deficient compared with copper-adequate animals. Associated with this copper deficiency were consistent reductions in immunoreactive SOD and robust enhancements in CCS. In most cases, the ratio of CCS:SOD was several-fold higher in red blood cell extracts from copper-deficient compared with copper-adequate rodents. Determination of red cell CCS:SOD may be useful for assessing copper status of humans.

Rosmarinic acid and antioxidant enzyme activities in Lavandula vera MM cell suspension culture: a comparative study.

PubMed

Georgiev, Milen; Abrashev, Radoslav; Krumova, Ekaterina; Demirevska, Klimentina; Ilieva, Mladenka; Angelova, Maria

2009-11-01

The growth and intracellular protein content of lavender (Lavandula vera MM) cell suspension culture was followed along with some antioxidant defense system members-non-enzymatic (rosmarinic acid) and enzymatic [superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6)]. It was found that the media content and the cultivation mode strongly influenced the production of plant defense compounds as well as the ratio between non-enzymatic and enzymatic ones. The bioreactor culture contains about two times more rosmarinic acid, superoxide dismutase, and catalase compared to the shake-flask cultivation. These findings are discussed with respect to the relative stress levels and plant antioxidant orchestra system. It was concluded that investigated defense system components (enzymatic and non-enzymatic) were closely associated in a complex balance. The three isoenzyme forms of SOD (Cu/ZnSOD, FeSOD, and MnSOD) in the cells of Lavandula vera were revealed by polyacrylamide gel electrophoresis analysis, and the FeSOD isoform exhibited highest activity.

Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.

PubMed

Hirata, H; Ladenheim, B; Carlson, E; Epstein, C; Cadet, J L

1996-04-01

Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve release of DA in presynaptic DA terminals, which is associated with increased formation of oxygen-based free radicals. We have recently shown that METH-induced striatal DA depletion is attenuated in transgenic (Tg) mice that express the human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically address the issue of loss of DA terminals. In the present study, we have used receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH caused decreases in striatal DA uptake sites in a dose-dependent fashion. The loss of DA terminals was more prominent in the lateral region than in the medial subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice showing the greatest protection. Female mice were somewhat more resistant than male mice against these deleterious effects of METH. These results provide further evidence for a role of superoxide radicals in the long-term effects of METH. They also suggest the notion of a gender-specific handling of oxidative stress.

Cerebellar Expression of Copper Chaperone for Superoxide, Cytosolic Cu/Zn-Superoxide Dismutase, 4-Hydroxy-2-Nonenal, Acrolein and Heat Shock Protein 32 in Patients with Menkes Kinky Hair Disease: Immunohistochemical Study

PubMed Central

Yokoyama, Atsushi; Ohno, Kousaku; Hirano, Asao; Shintaku, Masayuki; Kato, Masako; Hayashi, Kazuhiko; Kato, Shinsuke

2014-01-01

Background To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Methods Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Zn-superoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein 32 (hsp 32). Results The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. Conclusion In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism. PMID:25067875

Cerebellar expression of copper chaperone for superoxide, cytosolic cu/zn-superoxide dismutase, 4-hydroxy-2-nonenal, acrolein and heat shock protein 32 in patients with menkes kinky hair disease: immunohistochemical study.

PubMed

Yokoyama, Atsushi; Ohno, Kousaku; Hirano, Asao; Shintaku, Masayuki; Kato, Masako; Hayashi, Kazuhiko; Kato, Shinsuke

2014-03-01

To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Zn-superoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein 32 (hsp 32). The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism.

Altered serum copper homeostasis suggests higher oxidative stress and lower antioxidant capability in patients with chronic hepatitis B.

PubMed

Huang, Yansong; Zhang, Yuan; Lin, Zhexuan; Han, Ming; Cheng, Hongqiu

2018-06-01

Copper homeostasis can be altered by inflammation. This study aimed to investigate the alteration of serum copper homeostasis and to explore its clinical significance in patients with chronic hepatitis B (CHB).Thirty-two patients with CHB and 10 aged- and sex-matched healthy controls were recruited. Analyses included serum levels of total copper (TCu), copper ions (Cu), small molecule copper (SMC), ceruloplasmin (CP), Cu/Zn superoxide dismutase 1 (SOD1), urinary copper, and the activities of serum CP and SOD1.The serum TCu and urinary copper levels in patients with CHB were significantly higher than the controls (P = .04 and .003), while the serum Cu was lower than the controls (P = .0002). CP and SOD1 activities in the serum were significantly lower in patients with CHB compared to controls (P = .005) despite higher serum concentrations. In addition, serum alanine aminotransferase inversely correlated with serum CP activity (P = .0318, r = -0.4065).Serum copper homeostasis was altered in this cohort of patients with CHB. The results suggest increased oxidative stress and impaired antioxidant capability in patients with CHB, in addition to necroinflammation. These results may provide novel insights into the diagnosis and treatment of patients with CHB.

Import, maturation, and function of SOD1 and its copper chaperone CCS in the mitochondrial intermembrane space.

PubMed

Kawamata, Hibiki; Manfredi, Giovanni

2010-11-01

Cu, Zn, superoxide dismutase (SOD1) is a ubiquitous enzyme localized in multiple cellular compartments, including mitochondria, where it concentrates in the intermembrane space (IMS). Similar to other small IMS proteins, the import and retention of SOD1 in the IMS is linked to its folding and maturation, involving the formation of critical intra- and intermolecular disulfide bonds. Therefore, the cysteine residues of SOD1 play a fundamental role in its IMS localization. IMS import of SOD1 involves its copper chaperone, CCS, whose mitochondrial distribution is regulated by the Mia40/Erv1 disulfide relay system in a redox-dependent manner: CCS promotes SOD1 maturation and retention in the IMS. The function of SOD1 in the IMS is still unknown, but it is plausible that it serves to remove superoxide released from the mitochondrial respiratory chain. Mutations in SOD1 cause familial amyotrophic lateral sclerosis (ALS), whose pathologic features include mitochondrial bioenergetic dysfunction. Mutant SOD1 localization in the IMS is not dictated by oxygen concentration and the Mia40/Erv1 system, but is primarily dependent on aberrant protein folding and aggregation. Mutant SOD1 localization and aggregation in the IMS might cause the mitochondrial abnormalities observed in familial ALS and could play a significant role in disease pathogenesis.

Thermal fluctuations of immature SOD1 lead to separate folding and misfolding pathways

PubMed Central

Sekhar, Ashok; Rumfeldt, Jessica AO; Broom, Helen R; Doyle, Colleen M; Bouvignies, Guillaume; Meiering, Elizabeth M; Kay, Lewis E

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving cytotoxic conformations of Cu, Zn superoxide dismutase (SOD1). A major challenge in understanding ALS disease pathology has been the identification and atomic-level characterization of these conformers. Here, we use a combination of NMR methods to detect four distinct sparsely populated and transiently formed thermally accessible conformers in equilibrium with the native state of immature SOD1 (apoSOD12SH). Structural models of two of these establish that they possess features present in the mature dimeric protein. In contrast, the other two are non-native oligomers in which the native dimer interface and the electrostatic loop mediate the formation of aberrant intermolecular interactions. Our results show that apoSOD12SH has a rugged free energy landscape that codes for distinct kinetic pathways leading to either maturation or non-native association and provide a starting point for a detailed atomic-level understanding of the mechanisms of SOD1 oligomerization. DOI: http://dx.doi.org/10.7554/eLife.07296.001 PMID:26099300

Effects of Oridonin on growth performance and oxidative stress in broilers challenged with lipopolysaccharide.

PubMed

Zheng, X C; Wu, Q J; Song, Z H; Zhang, H; Zhang, J F; Zhang, L L; Zhang, T Y; Wang, C; Wang, T

2016-10-01

This study was conducted to investigate the effects of oridonin (ORI) on growth performance and antioxidant capacity in broiler chickens that were repeatedly challenged with lipopolysaccharide (LPS). A total of 384 one-day-old male Arbor Acre broiler chickens were randomly assigned to 8 treatments with 6 replicate cages per treatment and 8 birds per replicate. There were 4 dietary treatments: the control group (birds fed the basal diet), the ORI 50 group, the ORI 80 group, and the ORI 100 group (the basal diet supplemented with 50, 80, and 100 mg/kg oridonin, respectively). Broilers were intraperitoneally injected with either 250 μg/kg BW LPS or an equivalent amount of sterile saline at 16, 18, and 20 d of age. LPS decreased the average daily weight gain (ADG), the average daily feed intake (ADFI), and the feed conversion ratio (FCR) of broiler chickens (P < 0.05); oridonin supplementation had no effects on performance whether before or after LPS injection (P > 0.05). LPS stimulation increased the relative weight of the spleen and bursa (P < 0.05); oridonin inclusion markedly attenuated the increased spleen index (P < 0.05). Additionally, the LPS-induced increases in the concentrations of malondialdehyde (MDA) and decreases in activities of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) and catalase (CAT) were dramatically attenuated by oridonin in both the serum and liver (P < 0.05). Furthermore, LPS down-regulated the mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), copper and zinc superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx1), and CAT in the liver (P < 0.05), However, oridonin inclusion increased the liver mRNA expression levels of Nrf2, Cu/Zn-SOD, Mn-SOD, CAT, and GPx1 (P < 0.05). It was concluded that the dietary oridonin supplementation at an optimum dose of 100 mg/kg improves the antioxidant capacity in broilers, as evidenced by the decrease in MDA and the increase in total SOD activities and mRNA expression levels of the liver antioxidant genes, although the effects on growth performance was negligible. © Crown copyright 2016.

Phytotoxic effects of Cu, Cd and Zn on the seagrass Thalassia hemprichii and metal accumulation in plants growing in Xincun Bay, Hainan, China.

PubMed

Zheng, Jin; Gu, Xiao-Qian; Zhang, Tai-Jie; Liu, Hui-Hui; Ou, Qiao-Jing; Peng, Chang-Lian

2018-03-19

Seagrasses play an important role in coastal marine ecosystems, but they have been increasingly threatened by human activities. In recent years, seagrass communities have rapidly degenerated in the coastal marine ecosystems of China. To identify the reasons for the decline in seagrasses, the phytotoxic effects of trace metals (Cu, Cd and Zn) on the seagrass Thalassia hemprichii were investigated, and the environmental contents of the metals were analyzed where the seagrass grows. The results showed that leaf necrosis in T. hemprichii exposed to 0.01-0.1 mg L -1 of Cu 2+ for 5 days was more serious than that in plants exposed to the same concentrations of Cd 2+ and Zn 2+ . The chlorophyll content in T. hemprichii declined in a concentration-dependent manner after 5 days of exposure to Cu 2+ , Cd 2+ and Zn 2+ . The evident reduction in ΔF/F m ' in T. hemprichii leaves was observed at day 1 of exposure to 0.01-1.0 mg L -1 of Cu 2+ and at day 3 of exposure to 0.1-1.0 mg L -1 of Cd 2+ . The antioxidant enzyme activities (SOD, POD and CAT) in T. hemprichii leaves exposed to the three metal ions also showed significant changes. In seawater from Xincun Bay (Hainan, China), where T. hemprichii grows, Cu had reached a concentration (i.e., 0.01 mg L -1 ) that could significantly reduce chlorophyll content and ΔF/F m ' in T. hemprichii leaves. Our results indicate that Cu influences the deterioration of seagrasses in Xincun Bay.

Acylation of Superoxide Dismutase 1 (SOD1) at K122 Governs SOD1-Mediated Inhibition of Mitochondrial Respiration

PubMed Central

Banks, Courtney J.; Rodriguez, Nathan W.; Gashler, Kyle R.; Pandya, Rushika R.; Mortenson, Jeffrey B.; Whited, Matthew D.; Soderblom, Erik J.; Thompson, J. Will; Moseley, M. Arthur; Reddi, Amit R.; Tessem, Jeffery S.; Torres, Matthew P.; Bikman, Benjamin T.

2017-01-01

ABSTRACT In this study, we employed proteomics to identify mechanisms of posttranslational regulation on cell survival signaling proteins. We focused on Cu-Zn superoxide dismutase (SOD1), which protects cells from oxidative stress. We found that acylation of K122 on SOD1, while not impacting SOD1 catalytic activity, suppressed the ability of SOD1 to inhibit mitochondrial metabolism at respiratory complex I. We found that deacylase depletion increased K122 acylation on SOD1, which blocked the suppression of respiration in a K122-dependent manner. In addition, we found that acyl-mimicking mutations at K122 decreased SOD1 accumulation in mitochondria, initially hinting that SOD1 may inhibit respiration directly within the intermembrane space (IMS). However, surprisingly, we found that forcing the K122 acyl mutants into the mitochondria with an IMS-targeting tag did not recover their ability to suppress respiration. Moreover, we found that suppressing or boosting respiration levels toggled SOD1 in or out of the mitochondria, respectively. These findings place SOD1-mediated inhibition of respiration upstream of its mitochondrial localization. Lastly, deletion-rescue experiments show that a respiration-defective mutant of SOD1 is also impaired in its ability to rescue cells from toxicity caused by SOD1 deletion. Together, these data suggest a previously unknown interplay between SOD1 acylation, metabolic regulation, and SOD1-mediated cell survival. PMID:28739857

CCS and SOD1 mRNA are reduced after copper supplementation in peripheral mononuclear cells of individuals with high serum ceruloplasmin concentration.

PubMed

Suazo, Miriam; Olivares, Felipe; Mendez, Marco A; Pulgar, Rodrigo; Prohaska, Joseph R; Arredondo, Miguel; Pizarro, Fernando; Olivares, Manuel; Araya, Magdalena; González, Mauricio

2008-04-01

The limits of copper homeostatic regulation in humans are not known, making it difficult to define the milder effects of early copper excess. Furthermore, a robust assay to facilitate the detection of early stages of copper excess is needed. To address these issues, we assessed changes in relative mRNA abundance of methallothionein 2A (MT2A), prion (PrP), amyloid precursor-like protein 2 (APLP2), Cu/Zn superoxide dismutase (SOD1) and its copper chaperone (CCS) in peripheral mononuclear cells (PMNCs) from healthy adults representing the 5% highest and lowest extremes in the distribution curve of serum ceruloplasmin (Cp) concentrations of 800 individuals. The intracellular Cu content was also determined. PMNCs were isolated from individuals before and after exposure to a single daily dose of 10 mg Cu (as CuSO(4)) for 2 months. Results showed that although there were fluctuations in serum Cp values of the samples assessed before copper exposure, no significant differences were observed in cell copper content or in the relative abundance of MT2A, PrP and APLP2 transcripts in PMNCs. Also, these values were not modified after copper supplementation. However, CCS and SOD1 mRNA levels were reduced in PMNCs after copper supplementation in the individuals with the high Cp values, suggesting that they should be further explored as biomarkers of moderate copper overload in humans.

S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects.

PubMed

Antinone, Sarah E; Ghadge, Ghanashyam D; Ostrow, Lyle W; Roos, Raymond P; Green, William N

2017-01-25

Previously, we found that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyotrophic lateral sclerosis (ALS) mouse models, and that S-acylation increased for ALS-causing SOD1 mutants relative to wild type. Here, we use the acyl resin-assisted capture (acyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from ALS and non-ALS subjects. Acyl-RAC further revealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal cords, and in vitro in HEK293 cells. SOD1 and CCS formed a highly stable heterodimer in human spinal cord homogenates that was resistant to dissociation by boiling, denaturants, or reducing agents and was not observed in vitro unless both SOD1 and CCS were overexpressed. Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation. The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, and lowest for SOD1 monomers. Given that S-acylation facilitates anchoring of soluble proteins to cell membranes, our findings suggest that S-acylation and membrane localization may play an important role in CCS-mediated SOD1 maturation. Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturation intermediate in human spinal cord.

S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects

PubMed Central

Antinone, Sarah E.; Ghadge, Ghanashyam D.; Ostrow, Lyle W.; Roos, Raymond P.; Green, William N.

2017-01-01

Previously, we found that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyotrophic lateral sclerosis (ALS) mouse models, and that S-acylation increased for ALS-causing SOD1 mutants relative to wild type. Here, we use the acyl resin-assisted capture (acyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from ALS and non-ALS subjects. Acyl-RAC further revealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal cords, and in vitro in HEK293 cells. SOD1 and CCS formed a highly stable heterodimer in human spinal cord homogenates that was resistant to dissociation by boiling, denaturants, or reducing agents and was not observed in vitro unless both SOD1 and CCS were overexpressed. Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation. The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, and lowest for SOD1 monomers. Given that S-acylation facilitates anchoring of soluble proteins to cell membranes, our findings suggest that S-acylation and membrane localization may play an important role in CCS-mediated SOD1 maturation. Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturation intermediate in human spinal cord. PMID:28120938

Identifying Haemophilus haemolyticus and Haemophilus influenzae by SYBR Green real-time PCR.

PubMed

Latham, Roger; Zhang, Bowen; Tristram, Stephen

2015-05-01

SYBR Green real time PCR assays for protein D (hpd), fuculose kinase (fucK) and [Cu, Zn]-superoxide dismutase (sodC) were designed for use in an algorithm for the identification of Haemophilus influenzae and H. haemolyticus. When tested on 127 H. influenzae and 60 H. haemolyticus all isolates were identified correctly. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Identification Of Protein Vaccine Candidates Using Comprehensive Proteomic Analysis Strategies

DTIC Science & Technology

2007-12-01

urease (URE) gene codes for a urea amidohydrolase protein that catalyzes urea hydrolysis. The protein was first isolated from C. immitis and...the Cu, Zn, Superoxide Dismutase (SOD), the Spherule Outer Wall glycoprotein (SOWgp), the T-Cell Reactive Protein (TCRP), and Urease (URE). It is...et al. 1997. Isolation and characterization of the urease gene (URE) from the pathogenic fungus Coccidioides immitis. Gene 198: 387-391. 54. Li, K

Large SOD1 aggregates, unlike trimeric SOD1, do not impact cell viability in a model of amyotrophic lateral sclerosis.

PubMed

Zhu, Cheng; Beck, Matthew V; Griffith, Jack D; Deshmukh, Mohanish; Dokholyan, Nikolay V

2018-05-01

Aberrant accumulation of misfolded Cu, Zn superoxide dismutase (SOD1) is a hallmark of SOD1-associated amyotrophic lateral sclerosis (ALS), an invariably fatal neurodegenerative disease. While recent discovery of nonnative trimeric SOD1-associated neurotoxicity has suggested a potential pathway for motor neuron impairment, it is yet unknown whether large, insoluble aggregates are cytotoxic. Here we designed SOD1 mutations that specifically stabilize either the fibrillar form or the trimeric state of SOD1. The designed mutants display elevated populations of fibrils or trimers correspondingly, as demonstrated by gel filtration chromatography and electron microscopy. The trimer-stabilizing mutant, G147P, promoted cell death, even more potently in comparison with the aggressive ALS-associated mutants A4V and G93A. In contrast, the fibril-stabilizing mutants, N53I and D101I, positively impacted the survival of motor neuron-like cells. Hence, we conclude the SOD1 oligomer and not the mature form of aggregated fibril is critical for the neurotoxic effects in the model of ALS. The formation of large aggregates is in competition with trimer formation, suggesting that aggregation may be a protective mechanism against formation of toxic oligomeric intermediates.

Protective effect of [6]-gingerol on the ethanol-induced teratogenesis of cultured mouse embryos.

PubMed

Yon, Jung-Min; Baek, In-Jeoung; Lee, Se-Ra; Kim, Mi-Ra; Hong, Jin Tae; Yong, Hwanyul; Lee, Beom Jun; Yun, Young Won; Nam, Sang-Yoon

2012-01-01

Excessive ethanol consumption during pregnancy causes fetal alcohol syndrome. We investigated the effect of [6]-gingerol on ethanol-induced embryotoxicity using a whole embryo culture system. The morphological changes of embryos and the gene expression patterns of the antioxidant enzymes cytosolic glutathione peroxidase (cGPx), cytoplasmic Cu/Zn superoxide dismutase (SOD1), and Mn-SOD (SOD2), and SOD activity were examined in the cultured mouse embryos exposed to ethanol (5 μL/3 mL) and/or [6]-gingerol (1×10(-8) or 1×10(-7) μg/mL) for 2 days. In ethanol-exposed embryos, the standard morphological score of embryos was significantly decreased compared with those of the control (vehicle) group. However, cotreatment of embryos with [6]-gingerol and ethanol significantly improved all of the developmental parameters except crownrump length and head length, compared with those of the ethanol alone group. The mRNA expression levels of cGPx and SOD2, not SOD1, were decreased consistently, SOD activity were significantly decreased compared with the control group. However, the decreases in mRNA levels of antioxidant enzymes and SOD activity were significantly restored to the control levels by [6]-gingerol supplement. These results indicate that [6]-gingerol has a protective effect against ethanol-induced teratogenicity during mouse embryogenesis.

Use of Cu/Zn-superoxide dismutase tool for biomonitoring marine environment pollution in the Persian Gulf and the Gulf of Oman.

PubMed

Zeinali, Farrokhzad; Homaei, Ahmad; Kamrani, Ehsan; Patel, Seema

2018-04-30

Superoxide dismutase (SOD) is the pivotal antioxidant enzyme that defends organisms against the oxidative stresses of superoxide radicals. In this experimental study, purification of SOD from the leaves of Avicennia marina (grey mangrove or white mangrove) from the family Acanthaceae, located in Sirik mangrove forest on the shore of the Gulf of Oman was performed, for the intended characterization of SOD. The Sirik AmSOD (A. marina SOD) expressed optimum activity in the pH range of 6-9 with the maximum activity at pH 8. The optimal temperature for Sirik AmSOD activity was 70°C. Comparison of the pH and temperature optima in two regions (the Persian Gulf and the Gulf of Oman) showed significant differences with P<0.05. The SOD from the Persian Gulf was more resistant against the environmental stressors, because of the biochemical adaption to this environment, which is harsher. The evidence from these results suggests that AmSOD has different characteristics in each place, and mangroves undergo different adaptations and require different protections. The results of the enzymatic research can be useful for ecological management of organisms. Copyright © 2018 Elsevier Inc. All rights reserved.

Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo *

PubMed Central

Wang, Jun-ming; Sheng, Yu-chen; Ji, Li-li; Wang, Zheng-tao

2014-01-01

The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity. PMID:24903991

Determining the Effect of Catechins on SOD1 Conformation and Aggregation by Ion Mobility Mass Spectrometry Combined with Optical Spectroscopy

NASA Astrophysics Data System (ADS)

Zhao, Bing; Zhuang, Xiaoyu; Pi, Zifeng; Liu, Shu; Liu, Zhiqiang; Song, Fengrui

2018-02-01

The aggregation of Cu,Zn-superoxide dismutase (SOD1) plays an important role in the etiology of amyotrophic lateral sclerosis (ALS). For the disruption of ALS progression, discovering new drugs or compounds that can prevent SOD1 aggregation is important. In this study, ESI-MS was used to investigate the interaction of catechins and SOD1. The noncovalent complex of catechins that interact with SOD1 was found and retained in the gas phase under native ESI-MS condition. The conformation changes of SOD1 after binding with catechins were also explored via traveling wave ion mobility (IM) spectrometry. Epigallocatechin gallate (EGCG) can stabilize SOD1 conformation against unfolding in three catechins. To further evaluate the efficacy of EGCG, we monitored the fluorescence changes of dimer E2,E2,-SOD1(apo-SOD1, E:empty) with and without ligands under denaturation conditions, and found that EGCG can inhibit apo-SOD1 aggregation. In addition, the circular dichroism spectra of the samples showed that EGCG can decrease the β-sheet content of SOD1, which can produce aggregates. These results indicated that orthogonal separation dimension in the gas-phase IM coupled with ESI-MS (ESI-IM-MS) can potentially provide insight into the interaction between SOD1 and small molecules. The advantage is that it dramatically decreases the analysis time. Meantime, optical spectroscopy techniques can be used to confirm ESI-IM-MS results. [Figure not available: see fulltext.

Ceruloplasmin copper induces oxidant damage by a redox process utilizing cell-derived superoxide as reductant

NASA Technical Reports Server (NTRS)

Mukhopadhyay, C. K.; Fox, P. L.

1998-01-01

Oxidative damage by transition metals bound to proteins may be an important pathogenic mechanism. Ceruloplasmin (Cp) is a Cu-containing plasma protein thought to be involved in oxidative modification of lipoproteins. We have previously shown that Cp increased cell-mediated low-density lipoprotein (LDL) oxidation by a process requiring cell-derived superoxide, but the underlying chemical mechanism(s) is (are) unknown. We now show that superoxide reduction of Cp Cu is a critical reaction in cellular LDL oxidation. By bathocuproine disulfonate (BCS) binding and by superoxide utilization, we showed that exogenous superoxide reduces a single Cp Cu atom, the same Cu required for LDL oxidation. The Cu atom remained bound to Cp during the redox cycle. Three avenues of evidence showed that vascular cells reduce Cp Cu by a superoxide-dependent process. The 2-fold higher rate of Cp Cu reduction by smooth muscle cells (SMC) compared to endothelial cells (EC) was consistent with their relative rates of superoxide release. Furthermore, Cp Cu reduction by cells was blocked by Cu,Zn superoxide dismutase (SOD1). Finally, the level of superoxide produced by EC and SMC was sufficient to cause the amount of Cu reduction observed. An important role of Cp Cu reduction in LDL oxidation was suggested by results showing that SOD1 inhibited Cp Cu reduction and LDL oxidation by SMC with equal potency, while tumor necrosis factor-alpha stimulated both processes. In summary, these results show that superoxide is a critical cellular reductant of divalent transition metals involved in oxidation, and that protein-bound Cu is a substrate for this reaction. The role of these mechanisms in oxidative processes in vivo has yet to be defined.

TFE-induced local unfolding and fibrillation of SOD1: bridging the experiment and simulation studies.

PubMed

Kumar, Vijay; Prakash, Amresh; Pandey, Preeti; Lynn, Andrew M; Hassan, Md Imtaiyaz

2018-05-18

Misfolding and aggregation of Cu, Zn Superoxide dismutase (SOD1) is involved in the neurodegenerative disease, amyotrophic lateral sclerosis. Many studies have shown that metal-depleted, monomeric form of SOD1 displays substantial local unfolding dynamics and is the precursor for aggregation. Here, we have studied the structure and dynamics of different apo monomeric SOD1 variants associated with unfolding and aggregation in aqueous trifluoroethanol (TFE) through experiments and simulation. TFE induces partially unfolded β-sheet-rich extended conformations in these SOD1 variants, which subsequently develops aggregates with fibril-like characteristics. Fibrillation was achieved more easily in disulfide-reduced monomeric SOD1 when compared with wild-type and mutant monomeric SOD1. At higher concentrations of TFE, a native-like structure with the increase in α-helical content was observed. The molecular dynamics simulation results illustrate distinct structural dynamics for different regions of SOD1 variants and show uniform local unfolding of β-strands. The strands protected by the zinc-binding and electrostatic loops were found to unfold first in 20% (v/v) TFE, leading to a partial unfolding of β-strands 4, 5, and 6 which are prone to aggregation. Our results thus shed light on the role of local unfolding and conformational dynamics in SOD1 misfolding and aggregation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Biological effects of CCS in the absence of SOD1 enzyme activation: implications for disease in a mouse model for ALS.

PubMed

Proescher, Jody B; Son, Marjatta; Elliott, Jeffrey L; Culotta, Valeria C

2008-06-15

The CCS copper chaperone is critical for maturation of Cu, Zn-superoxide dismutase (SOD1) through insertion of the copper co-factor and oxidization of an intra-subunit disulfide. The disulfide helps stabilize the SOD1 polypeptide, which can be particularly important in cases of amyotrophic lateral sclerosis (ALS) linked to misfolding of mutant SOD1. Surprisingly, however, over-expressed CCS was recently shown to greatly accelerate disease in a G93A SOD1 mouse model for ALS. Herein we show that disease in these G93A/CCS mice correlates with incomplete oxidation of the SOD1 disulfide. In the brain and spinal cord, CCS over-expression failed to enhance oxidation of the G93A SOD1 disulfide and if anything, effected some accumulation of disulfide-reduced SOD1. This effect was mirrored in culture with a C244,246S mutant of CCS that has the capacity to interact with SOD1 but can neither insert copper nor oxidize the disulfide. In spite of disulfide effects, there was no evidence for increased SOD1 aggregation. If anything, CCS over-expression prevented SOD1 misfolding in culture as monitored by detergent insolubility. This protection against SOD1 misfolding does not require SOD1 enzyme activation as the same effect was obtained with the C244,246S allele of CCS. In the G93A SOD1 mouse, CCS over-expression was likewise associated with a lack of obvious SOD1 misfolding marked by detergent insolubility. CCS over-expression accelerates SOD1-linked disease without the hallmarks of misfolding and aggregation seen in other mutant SOD1 models. These studies are the first to indicate biological effects of CCS in the absence of SOD1 enzymatic activation.

Insights into the role of the unusual disulfide bond in copper-zinc superoxide dismutase.

PubMed

Sea, Kevin; Sohn, Se Hui; Durazo, Armando; Sheng, Yuewei; Shaw, Bryan F; Cao, Xiaohang; Taylor, Alexander B; Whitson, Lisa J; Holloway, Stephen P; Hart, P John; Cabelli, Diane E; Gralla, Edith Butler; Valentine, Joan Selverstone

2015-01-23

The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. We determined x-ray crystal structures of metal-bound and metal-deficient hC57S SOD1. C57S hSOD1 isolated from yeast contained four zinc ions per protein dimer and was structurally very similar to wild type. The addition of copper to this four-zinc protein gave properly reconstituted 2Cu,2Zn C57S hSOD, and its spectroscopic properties indicated that the coordination geometry of the copper was remarkably similar to that of holo wild type hSOD1. In contrast, the addition of copper and zinc ions to apo C57S human SOD1 failed to give proper reconstitution. Using pulse radiolysis, we determined SOD activities of yeast and human SOD1s lacking disulfide bonds and found that they were enzymatically active at ∼10% of the wild type rate. These results are contrary to earlier reports that the intrasubunit disulfide bonds in SOD1 are essential for SOD activity. Kinetic studies revealed further that the yeast mutant SOD1 had less ionic attraction for superoxide, possibly explaining the lower rates. Saccharomyces cerevisiae cells lacking the sod1 gene do not grow aerobically in the absence of lysine, but expression of C57S SOD1 increased growth to 30-50% of the growth of cells expressing wild type SOD1, supporting that C57S SOD1 retained a significant amount of activity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Insights into the Role of the Unusual Disulfide Bond in Copper-Zinc Superoxide Dismutase*

PubMed Central

Sea, Kevin; Sohn, Se Hui; Durazo, Armando; Sheng, Yuewei; Shaw, Bryan F.; Cao, Xiaohang; Taylor, Alexander B.; Whitson, Lisa J.; Holloway, Stephen P.; Hart, P. John; Cabelli, Diane E.; Gralla, Edith Butler; Valentine, Joan Selverstone

2015-01-01

The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. We determined x-ray crystal structures of metal-bound and metal-deficient hC57S SOD1. C57S hSOD1 isolated from yeast contained four zinc ions per protein dimer and was structurally very similar to wild type. The addition of copper to this four-zinc protein gave properly reconstituted 2Cu,2Zn C57S hSOD, and its spectroscopic properties indicated that the coordination geometry of the copper was remarkably similar to that of holo wild type hSOD1. In contrast, the addition of copper and zinc ions to apo C57S human SOD1 failed to give proper reconstitution. Using pulse radiolysis, we determined SOD activities of yeast and human SOD1s lacking disulfide bonds and found that they were enzymatically active at ∼10% of the wild type rate. These results are contrary to earlier reports that the intrasubunit disulfide bonds in SOD1 are essential for SOD activity. Kinetic studies revealed further that the yeast mutant SOD1 had less ionic attraction for superoxide, possibly explaining the lower rates. Saccharomyces cerevisiae cells lacking the sod1 gene do not grow aerobically in the absence of lysine, but expression of C57S SOD1 increased growth to 30–50% of the growth of cells expressing wild type SOD1, supporting that C57S SOD1 retained a significant amount of activity. PMID:25433341

Copper transport and trafficking at the host-bacterial pathogen interface.

PubMed

Fu, Yue; Chang, Feng-Ming James; Giedroc, David P

2014-12-16

CONSPECTUS: The human innate immune system has evolved the means to reduce the bioavailability of first-row late d-block transition metal ions to invading microbial pathogens in a process termed "nutritional immunity". Transition metals from Mn(II) to Zn(II) function as metalloenzyme cofactors in all living cells, and the successful pathogen is capable of mounting an adaptive response to mitigate the effects of host control of transition metal bioavailability. Emerging evidence suggests that Mn, Fe, and Zn are withheld from the pathogen in classically defined nutritional immunity, while Cu is used to kill invading microorganisms. This Account summarizes new molecular-level insights into copper trafficking across cell membranes from studies of a number of important bacterial pathogens and model organisms, including Escherichia coli, Salmonella species, Mycobacterium tuberculosis, and Streptococcus pneumoniae, to illustrate general principles of cellular copper resistance. Recent highlights of copper chemistry at the host-microbial pathogen interface include the first high resolution structures and functional characterization of a Cu(I)-effluxing P1B-ATPase, a new class of bacterial copper chaperone, a fungal Cu-only superoxide dismutase SOD5, and the discovery of a small molecule Cu-bound SOD mimetic. Successful harnessing by the pathogen of host-derived bactericidal Cu to reduce the bacterial load of reactive oxygen species (ROS) is an emerging theme; in addition, recent studies continue to emphasize the importance of short lifetime protein-protein interactions that orchestrate the channeling of Cu(I) from donor to target without dissociation into bulk solution; this, in turn, mitigates the off-pathway effects of Cu(I) toxicity in both the periplasm in Gram negative organisms and in the bacterial cytoplasm. It is unclear as yet, outside of the photosynthetic bacteria, whether Cu(I) is trafficked to other cellular destinations, for example, to cuproenzymes or other intracellular storage sites, or the general degree to which copper chaperones vs copper efflux transporters are essential for bacterial pathogenesis in the vertebrate host. Future studies will be directed toward the identification and structural characterization of other cellular targets of Cu(I) trafficking and resistance, the physical and mechanistic characterization of Cu(I)-transfer intermediates, and elucidation of the mutual dependence of Cu(I) trafficking and cellular redox status on thiol chemistry in the cytoplasm. Crippling bacterial control of Cu(I) sensing, trafficking, and efflux may represent a viable strategy for the development of new antibiotics.

Nitric oxide is a mediator of methamphetamine (METH)-induced neurotoxicity. In vitro evidence from primary cultures of mesencephalic cells.

PubMed

Sheng, P; Cerruti, C; Ali, S; Cadet, J L

1996-10-31

METH is a monoaminergic toxic that destroys dopamine terminals in vivo. Oxidative mechanisms associated with DA metabolism are thought to play an important role in its toxic effects. These ideas were supported by the demonstration that CuZn-superoxide dismutase (CuZnSOD) transgenic mice were protected against the toxic effects of the drug. In the present study, we sought to determine if nitric oxide (NO) production was also involved in METH-induced neurotoxicity using primary cultures obtained from fetal rat mesencephalon. METH caused dose- and time-dependent cell death in vitro. Blockade of nitric oxide (NO) formation with several nitric oxide (NO) synthase blockers attenuated METH-mediated toxicity. Moreover, inhibition of ADP-ribosylation with nicotinamide and benzamide also provided protection against the toxicity of the drug. These results, together with our previous results in transgenic mice, support a role for free radicals in METH-induced toxic effects.

Species-specific activation of Cu/Zn SOD by its CCS copper chaperone in the pathogenic yeast Candida albicans.

PubMed

Gleason, Julie E; Li, Cissy X; Odeh, Hana M; Culotta, Valeria C

2014-06-01

Candida albicans is a pathogenic yeast of important public health relevance. Virulence of C. albicans requires a copper and zinc containing superoxide dismutase (SOD1), but the biology of C. albicans SOD1 is poorly understood. To this end, C. albicans SOD1 activation was examined in baker's yeast (Saccharomyces cerevisiae), a eukaryotic expression system that has proven fruitful for the study of SOD1 enzymes from invertebrates, plants, and mammals. In spite of the 80% similarity between S. cerevisiae and C. albicans SOD1 molecules, C. albicans SOD1 is not active in S. cerevisiae. The SOD1 appears incapable of productive interactions with the copper chaperone for SOD1 (CCS1) of S. cerevisiae. C. albicans SOD1 contains a proline at position 144 predicted to dictate dependence on CCS1. By mutation of this proline, C. albicans SOD1 gained activity in S. cerevisiae, and this activity was independent of CCS1. We identified a putative CCS1 gene in C. albicans and created heterozygous and homozygous gene deletions at this locus. Loss of CCS1 resulted in loss of SOD1 activity, consistent with its role as a copper chaperone. C. albicans CCS1 also restored activity to C. albicans SOD1 expressed in S. cerevisiae. C. albicans CCS1 is well adapted for activating its partner SOD1 from C. albicans, but not SOD1 from S. cerevisiae. In spite of the high degree of homology between the SOD1 and CCS1 molecules in these two fungal species, there exists a species-specific barrier in CCS-SOD interactions which may reflect the vastly different lifestyles of the pathogenic versus the noninfectious yeast.

The effect of amyotrophic lateral sclerosis-linked exogenous SOD1-G93A on electrophysiological properties and intracellular calcium in cultured rat astrocytes.

PubMed

Milošević, Milena; Bataveljić, Danijela; Nikolić, Ljiljana; Bijelić, Dunja; Andjus, Pavle

2016-01-01

Over 150 mutations in the SOD1 gene that encodes Cu/Zn superoxide dismutase (SOD1) cause 20-25% of familial ALS, albeit without a known gain-of-function mechanism. ALS is also non-cell-autonomous, the interactions between motor neurons and their glial neighbours being implicated in disease progression. The aim here was to investigate the biophysical effects of the exogenous human mutant SOD1-G93A on rat astrocytes in culture. Primary cortical astrocyte cultures were treated with recombinant human apo- mSOD1-G93A vs. wild-type control (wtSOD1) and recorded by patch-clamp and calcium imaging. Results showed that exogenous mSOD1 as well as wtSOD1 induced a decrease of membrane resistance, the effect being persistent (up to 13 min) only for the mutant form. Similarly, whole-cell inward currents in astrocytes were augmented by both wt and mSOD1, but the effect was twice larger and only progressed continuously for the latter. Both forms of SOD1 also induced a rise in intracellular Ca(2+) activity, the effect being dependent on external Ca(2+) and again only persisted with mSOD1, becoming significantly different from wtSOD1 only at longer times (14 min). In conclusion, this study points to membrane permeability and Ca(2+) signalling as processes affected by SOD1-G93A that presents the humoral factor triggering the role of astrocytes in ALS pathophysiology.

Cross-Reactivity of Schistosoma mansoni Cytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

PubMed Central

Carvalho-Queiroz, Claudia; Cook, Rosemary; Wang, Ching C.; Correa-Oliveira, Rodrigo; Bailey, Nicola A.; Egilmez, Nejat K.; Mathiowitz, Edith; LoVerde, Philip T.

2004-01-01

Schistosoma mansoni, an intravascular parasite, has evolved a number of immune evasion mechanisms to establish itself in the host, such as antioxidant enzymes. Our laboratory has demonstrated that the highest levels of certain antioxidant enzymes are found in adult worms, which are the least susceptible to immune killing. Vaccination of mice with naked DNA constructs containing the gene encoding Cu/Zn cytosolic superoxide dismutase (SmCT-SOD) showed significant levels of protection compared to a control group, and our data demonstrate that the adult worms are a target of the immune response that confers resistance in SmCT-SOD DNA-vaccinated mice. Because SmCT-SOD shows significant identity with the human homologue, we evaluated the reactivity of anti-SmCT-SOD antibodies derived from SmCT-SOD-immunized mice and rabbits and from S. mansoni-infected individuals to human superoxide dismutase (hSOD) and SmCT-SOD parasite-specific peptides to assess the potential for autoimmune responses from immunization with the recombinant molecule. In addition, we evaluated the ability of various SmCT-SOD adjuvant-delivered immunizations to induce cross-reactive antibodies. Both mouse and rabbit antibodies generated against SmCT-SOD recognized the denatured form of hSOD. The same antibodies did not recognize nondenatured hSOD. Sera from infected individuals with different clinical forms of schistosomiasis recognized SmCT-SOD but not hSOD. Antibodies from mice immunized with different SmCT-SOD-containing formulations of both DNA and protein were able to recognize SmCT-SOD-derived peptides but not soluble hSOD. All together, these findings serve as a basis for developing a subunit vaccine against schistosomiasis. PMID:15102772

Effects of dietary selenium, vitamin E, and their combination on growth, serum metabolites, and antioxidant defense system in skeletal muscle of broilers under heat stress.

PubMed

Ghazi Harsini, Shahab; Habibiyan, Mahmood; Moeini, Mohammad Mehdi; Abdolmohammadi, Ali Reza

2012-09-01

This experiment was conducted to evaluate the effects of dietary vitamin E, selenium (Se), and a combination of the two, on the performance, serum metabolites and oxidative stability of skeletal muscle of broilers during heat stress. The broilers raised in either a thermoneutral (23.9°C constant) or heat stress (23.9°C to 37°C cycling) environment were assigned to 6 dietary treatments (0, 0.5, or 1 mg/kg Se; 125 and 250 mg/kg vitamin E; or 0.5 mg/kg Se plus 125 mg/kg vitamin E) from 1 to 49 days of age. At the end of the experiment, blood samples were collected from chicks, the chicks sacrificed, and pectoralis superficialis muscle was used for measurement of malondialdehyde (MDA) concentration and enzyme activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). The heat-stressed chicks consumed less feed, gained less weight, and had higher feed conversion ratio when compared to thermoneutral chicks (P<0.05). Serum concentrations of iron (Fe) and zinc (Zn) were decreased by heat stress (P<0.05), whereas the serum concentrations of copper (Cu), glucose, and uric acid were significantly increased under heat stress (P<0.05). The chicks that received supplemental of vitamin E exhibited significantly higher serum concentrations of Zn (P<0.05) and significantly lower concentrations of Cu, glucose, and uric acid (P<0.05) when exposed to heat stress. Dietary Se also caused a significant decrease in serum glucose, uric acid, and Cu concentrations of heat-stressed broilers (P<0.05), but had no significant effect on Zn concentration (P>0.05). The GPx activity remained relatively constant (P>0.05), though SOD activity and MDA levels in skeletal muscle were enhanced on exposure to heat stress (P<0.05). The heat-stressed chicks that received the combined supplementary level of vitamin E and Se had the lowest concentration of MDA and the highest activity of SOD in the skeletal muscle (P<0.05). Dietary Se also caused a significant increase in enzyme activity of GPx in the skeletal muscle (P<0.05). These results indicate that the derangement of blood parameters and oxidative stability in broilers under heat stress are improved by supplemental vitamin E and Se.

Effect of Cu(II) coordination compounds on the activity of antioxidant enzymes catalase and superoxide dismutase in patients with colorectal cancer.

PubMed

Kubiak, Katarzyna; Malinowska, Katarzyna; Langer, Ewa; Dziki, Łukasz; Dziki, Adam; Majsterek, Ireneusz

2011-03-01

Colorectal cancer (CRC) is a serious medical and economical problem of our times. It is the most common gastrointestinal cancer in the world. In Poland, the treatment and detection of CRC are poorly developed and the pathogenesis is still unclear. One hypothesis suggests a role of reactive oxygen species (ROS) in the pathogenesis of CRC. Experimental studies in recent years confirm the participation of ROS in the initiation and promotion of CRC. The aim of the study was to examine the effect of the following coordination compounds coordination compounds: dinitrate (V) tetra(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dinitrate (V) di(1,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(1,3,4,5-tetramethyl-N1-pyrazole-κN2) copper(II) on the activity of antioxidant enzymes superoxide dismutase (SOD, ZnCu-SOD) and catalase (CAT) in a group of patients with colorectal cancer (CRC) and in the control group consisting of patients with minor gastrointestinal complaints. The study was conducted in 20 patients diagnosed with colorectal cancer at the age of 66.5±10.2 years (10 men and 10 women) versus the control group of 20 people (10 men and 10 women) aged 57.89±17.10 years without cancer lesions in the biological material - hemolysate prepared in a proportion of 1ml of water per 1 ml of blood. CAT activity was measured by the Beers method (1952), while SOD activity was measured by the Misra and Fridovich method (1972). We found that patients with CRC showed a statistically significant decrease of SOD and CAT activity (CAT - 12,75±1.97 U/g Hb, SOD - 1111.52±155.52 U/g Hb) in comparison with the control group (CAT - 19.65±2,17 U/g Hb, SOD - 2046.26±507.22 U/g Hb). Simultaneously, we observed that the investigated coordination compounds of Cu(II) significantly increased the antioxidant activity of CAT and SOD in patients with CRC (mean: CAT 25.23±4.86 U/g Hb, SOD - 3075.96±940.20 U/g Hb). Patients with colorectal cancer are characterized by reduced activity of antioxidant enzymes catalase and superoxide dismutase which suggests impaired antioxidant barrier. Therefore, coordination compounds of Cu (II), which enhance the activity of CAT and SOD, may prove useful in the prevention and treatment of colorectal cancer.

TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma.

PubMed

Nadeem, Ahmed; Siddiqui, Nahid; Al-Harbi, Naif O; Al-Harbi, Mohammed M; Ahmad, Sheikh F

2016-04-01

Toll-like receptors (TLRs) through innate immune system recognize pathogen associated molecular patterns and play an important role in host defense against bacteria, fungi and viruses. TLR-7 is responsible for sensing single stranded nucleic acids of viruses but its activation has been shown to be protective in mouse models of asthma. The NADPH oxidase (NOX) enzymes family mainly produces reactive oxygen species (ROS) in the lung and is involved in regulation of airway inflammation in response to TLRs activation. However, NOX-4 mediated signaling in response to TLR-7 activation in a mouse model of allergic asthma has not been explored previously. Therefore, this study investigated the role TLR-7 activation and downstream oxidant-antioxidant signaling in a murine model of asthma. Mice were sensitized with ovalbumin (OVA) intraperitoneally and treated with TLR-7 agonist, resiquimod (RSQ) intranasally before each OVA challenge from days 14 to 16. Mice were then assessed for airway reactivity, inflammation, and NOX-4 and nuclear factor E2-related factor 2 (Nrf2) related signaling [inducible nitric oxide synthase (iNOS), nitrotyrosine, lipid peroxides and copper/zinc superoxide dismutase (Cu/Zn SOD)]. Treatment with RSQ reduced allergen induced airway reactivity and inflammation. This was paralleled by a decrease in ROS which was due to induction of Nrf2 and Cu/Zn SOD in RSQ treated group. Inhibition of MyD88 reversed RSQ-mediated protective effects on airway reactivity/inflammation due to reduction in Nrf2 signaling. SOD inhibition produced effects similar to MyD88 inhibition. The current study suggests that TLR-7 agonist is beneficial and may be developed into a therapeutic option in allergic asthma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced Detection of Sub-Retinal Pigment Epithelial Cell Layer Deposits in Human and Murine Tissue: Imaging Zinc as a Biomarker for Age-Related Macular Degeneration (An American Ophthalmological Society Thesis).

PubMed

van Kuijk, Frederik J G M; McPherson, Scott W; Roehrich, Heidi

2017-08-01

Understanding the apparent paradoxical role of zinc in the pathogenesis and prevention of age-related macular degeneration (AMD) has been limited by the lack of animal models for its detection in sub-retinal epithelial deposits (drusen), a definitive early hallmark of AMD. In-vitro studies using Zinpyr-1 showed drusen contained high levels of zinc, but the probe was not suitable for in-vivo studies. This study compares Zinpyr-1 to ZPP1, a new fluorescein-based probe for zinc, to assess the potential of ZPP1 for in-vivo detection of zinc in drusen. Flat mounts of human sub-RPE tissue using the probes were analyzed by fluorescence and confocal microscopy. Flat mounts of sub-RPE tissue from mice deficient in superoxide dismutase isoform-1 (CuZn-SOD-KO) or isoform-2 (Mn-SOD-RPE-KO) were analyzed with sub-RPE deposits confirmed by histology. Drusen are detected in greater numbers and intensity with ZPP1 compared to Zinpyr-1. Using ZPP1, drusen was detected in a sample from a 46-year old human donor without ocular history, suggesting that ZPP1 might be sensitive enough to detect drusen at an early stage. With CuZn-SOD KO mice, ZPP1 detected sub-RPE deposits at 10 months of age, whereas Zinpyr-1 required 14 months. Detection of sub-RPE deposits by ZPP1 was greatly enhanced compared to Zinpyr-1. This enhanced sensitivity will allow for more insightful analysis of zinc in AMD using human specimens and mouse models. This could result in the development of a sensitive in-vivo probe to enhance research on the role zinc in drusen formation and the early clinical diagnosis of AMD.

Low pH-Induced Changes of Antioxidant Enzyme and ATPase Activities in the Roots of Rice (Oryza sativa L.) Seedlings

PubMed Central

Zhang, Yi-Kai; Zhu, De-Feng; Zhang, Yu-Ping; Chen, Hui-Zhe; Xiang, Jing; Lin, Xian-Qing

2015-01-01

Soil acidification is the main problem in the current rice production. Here, the effects of low pH on the root growth, reactive oxygen species metabolism, plasma membrane functions, and the transcript levels of the related genes were investigated in rice seedlings (Oryza sativa L.) in a hydroponic system at pH 3.5, 4.5, and 5.5. There were two hybrid rice cultivars in this trial, including Yongyou 12 (YY12, a japonica hybrid) and Zhongzheyou 1 (ZZY1, an indica hybrid). Higher H+ activity markedly decreased root length, the proportion of fine roots, and dry matter production, but induced a significant accumulation of hydrogen peroxide (H2O2), and led to serious lipid peroxidation in the roots of the two varieties. The transcript levels of copper/zinc superoxide dismutase 1 (Cu/Zn SOD1), copper/zinc superoxide dismutase 2 (Cu/Zn SOD2), catalase A (CATA) and catalase B (CATB) genes in YY12 and ZZY1 roots were significantly down-regulated after low pH exposure for two weeks. Meanwhile, a significant decrease was observed in the expression of the P-type Ca2+-ATPases in roots at pH 3.5. The activities of antioxidant enzymes (SOD, CAT) and plasma membrane (PM) Ca2+-ATPase in the two varieties were dramatically inhibited by strong rhizosphere acidification. However, the expression levels of ascorbate peroxidase 1 (APX1) and PM H+-ATPase isoform 7 were up-regulated under H+ stress compared with the control. Significantly higher activities of APX and PM H+-ATPase could contribute to the adaptation of rice roots to low pH. PMID:25719552

Identification of a misfolded region in superoxide dismutase 1 that is exposed in amyotrophic lateral sclerosis.

PubMed

Rotunno, Melissa S; Auclair, Jared R; Maniatis, Stephanie; Shaffer, Scott A; Agar, Jeffrey; Bosco, Daryl A

2014-10-10

Mutations and aberrant post-translational modifications within Cu,Zn-superoxide dismutase (SOD1) cause this otherwise protective enzyme to misfold, leading to amyotrophic lateral sclerosis (ALS). The C4F6 antibody selectively binds misfolded SOD1 in spinal cord tissues from postmortem human ALS cases, as well as from an ALS-SOD1 mouse model, suggesting that the C4F6 epitope reports on a pathogenic conformation that is common to misfolded SOD1 variants. To date, the residues and structural elements that comprise this epitope have not been elucidated. Using a chemical cross-linking and mass spectrometry approach, we identified the C4F6 epitope within several ALS-linked SOD1 variants, as well as an oxidized form of WT SOD1, supporting the notion that a similar misfolded conformation is shared among pathological SOD1 proteins. Exposure of the C4F6 epitope was modulated by the SOD1 electrostatic (loop VII) and zinc binding (loop IV) loops and correlated with SOD1-induced toxicity in a primary microglia activation assay. Site-directed mutagenesis revealed Asp(92) and Asp(96) as key residues within the C4F6 epitope required for the SOD1-C4F6 binding interaction. We propose that stabilizing the functional loops within SOD1 and/or obscuring the C4F6 epitope are viable therapeutic strategies for treating SOD1-mediated ALS. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Palmitoylation of superoxide dismutase 1 (SOD1) is increased for familial amyotrophic lateral sclerosis-linked SOD1 mutants.

PubMed

Antinone, Sarah E; Ghadge, Ghanashyam D; Lam, Tukiet T; Wang, Lijun; Roos, Raymond P; Green, William N

2013-07-26

Mutations in Cu,Zn-superoxide dismutase (mtSOD1) cause familial amyotrophic lateral sclerosis (FALS), a neurodegenerative disease resulting from motor neuron degeneration. Here, we demonstrate that wild type SOD1 (wtSOD1) undergoes palmitoylation, a reversible post-translational modification that can regulate protein structure, function, and localization. SOD1 palmitoylation was confirmed by multiple techniques, including acyl-biotin exchange, click chemistry, cysteine mutagenesis, and mass spectrometry. Mass spectrometry and cysteine mutagenesis demonstrated that cysteine residue 6 was the primary site of palmitoylation. The palmitoylation of FALS-linked mtSOD1s (A4V and G93A) was significantly increased relative to that of wtSOD1 expressed in HEK cells and a motor neuron cell line. The palmitoylation of FALS-linked mtSOD1s (G93A and G85R) was also increased relative to that of wtSOD1 when assayed from transgenic mouse spinal cords. We found that the level of SOD1 palmitoylation correlated with the level of membrane-associated SOD1, suggesting a role for palmitoylation in targeting SOD1 to membranes. We further observed that palmitoylation occurred predominantly on disulfide-reduced as opposed to disulfide-bonded SOD1, suggesting that immature SOD1 is the primarily palmitoylated species. Increases in SOD1 disulfide bonding and maturation with increased copper chaperone for SOD1 expression caused a decrease in wtSOD1 palmitoylation. Copper chaperone for SOD1 overexpression decreased A4V palmitoylation less than wtSOD1 and had little effect on G93A mtSOD1 palmitoylation. These findings suggest that SOD1 palmitoylation occurs prior to disulfide bonding during SOD1 maturation and that palmitoylation is increased when disulfide bonding is delayed or decreased as observed for several mtSOD1s.

Biomarkers of Oxidative Stress and Heavy Metal Levels as Indicators of Environmental Pollution in African Cat Fish (Clarias gariepinus) from Nigeria Ogun River

PubMed Central

Farombi, E. O.; Adelowo, O. A.; Ajimoko, Y. R.

2007-01-01

Levels of Zn, Cu, Cd, As, and Pb in the kidney, Liver, Gills and Heart of African cat fish (Clarias gariepinus) from the Ogun River in Ogun State located close to six major industries in the South Western part of Nigeria, were determined using Bulk Scientific Atomic Absorption Spectrophotometer. Fishes were also collected from Government owned fish farm in Agodi, Ibadan which was considered a reference site. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione (GSH) concentration and malondialdehyde (MDA) formation were also determined. The trend of accumulation of the metals in the organs is as follows: Heart - Zn > Cu > Pb > As > Cd; Gills - Zn > Cu > Pb > Cd > As; Kidney - Zn > Cu > Pb > As > Cd; Liver -Zn > Cu > Pb > As > Cd. The order of concentration of the metals in the organs is as follows: Arsenite - Kidney > Liver > Gills > Heart; Zinc - Gills > Liver > Kidney > Heart; Lead- Liver > Kidney > Gills > Heart; Copper- Kidney > Liver > Gills > Heart; Cadmium > Liver > Gills > Kidney > Heart. The levels of heavy metals ranged between 0.25–8.96 ppm in the heart, 0.69– 19.05 ppm in the kidneys, 2.10–19.75 ppm in the liver and 1.95–20.35 ppm in the gills. SOD activity increased by 61% in the liver, 50% in the kidney and in the heart by 28 % while a significant decrease (44%) was observed in the gill of Clarias gariepinus from Ogun river compared to that Agodi fish farm (P<0.001). On the contrary there was 46%, 41%, 50% and 19% decrease in CAT activity in the liver, kidney, gills and heart respectively. The levels of GST activities in the liver, kidney and heart of Clarias gariepinus from Ogun river increased by 62%, 72% and 37% respectively (P<0.001) whereas there was a significant decrease (41%) in the gills (P<0.05) compared to that from the Agodi fish farm. GSH concentration increased by 81%, 83% and 53% in the liver, kidney and heart respectively but decreased by 44% in the gills. MDA levels of Clarias gariepinus were significantly (P<0.001) elevated in the liver, kidney, gills and heart by 177%, 102%, 168% and 71% respectively compared to that from Agodi fish farm. Overall, the results demonstrate that alteration in the antioxidant enzymes, glutathione system and induction of lipid peroxidation reflects the presence of heavy metals which may cause oxidative stress in the Clarias gariepinus from Ogun River. The study therefore provides a rational use of biomarkers of oxidative stress in biomonitoring of aquatic pollution. PMID:17617680

Evidence for the Cost of Reproduction in Humans: High Lifetime Reproductive Effort Is Associated with Greater Oxidative Stress in Post-Menopausal Women

PubMed Central

Sancilio, Amelia; Galbarczyk, Andrzej; Klimek, Magdalena

2016-01-01

Life history theory predicts trade-offs between reproductive effort and maternal survivorship in energy-restricted environments. However, empirical evidence for the positive association between maternal mortality and reproductive effort from energetically challenged human populations are mixed and physiological mechanisms that may underlie this association are poorly understood. We hypothesized that increases in aerobic metabolism during repeated periods of pregnancy and lactation result in increased oxidative stress that may contribute to somatic deterioration, vulnerability to illness, and accelerated aging. We therefore predicted that lifetime gravidity and parity would be related to levels of biomarkers of oxidative stress, as well as antioxidative defence enzymes in post-menopausal women. Our hypothesis was supported by positive linear associations between levels of 8-OHdG, a biomarker of DNA oxidative damage (β = 0.21, p<0.05), levels of antioxidative defence enzyme Cu-Zn SOD (β = 0.25, p<0.05), and number of lifetime pregnancies. Furthermore, independent of age and health status, post-menopausal women with higher gravidity and parity (> = 4 pregnancies per lifetime) had 20% higher levels of 8-OHdG and 60% higher levels of Cu-Zn SOD compared to women with lower gravidity and parity (<4 pregnancies per lifetime). Our results present the first evidence for oxidative stress as a possible cost of reproductive effort in humans. PMID:26761206

Evidence for the Cost of Reproduction in Humans: High Lifetime Reproductive Effort Is Associated with Greater Oxidative Stress in Post-Menopausal Women.

PubMed

Ziomkiewicz, Anna; Sancilio, Amelia; Galbarczyk, Andrzej; Klimek, Magdalena; Jasienska, Grazyna; Bribiescas, Richard G

2016-01-01

Life history theory predicts trade-offs between reproductive effort and maternal survivorship in energy-restricted environments. However, empirical evidence for the positive association between maternal mortality and reproductive effort from energetically challenged human populations are mixed and physiological mechanisms that may underlie this association are poorly understood. We hypothesized that increases in aerobic metabolism during repeated periods of pregnancy and lactation result in increased oxidative stress that may contribute to somatic deterioration, vulnerability to illness, and accelerated aging. We therefore predicted that lifetime gravidity and parity would be related to levels of biomarkers of oxidative stress, as well as antioxidative defence enzymes in post-menopausal women. Our hypothesis was supported by positive linear associations between levels of 8-OHdG, a biomarker of DNA oxidative damage (β = 0.21, p<0.05), levels of antioxidative defence enzyme Cu-Zn SOD (β = 0.25, p<0.05), and number of lifetime pregnancies. Furthermore, independent of age and health status, post-menopausal women with higher gravidity and parity (> = 4 pregnancies per lifetime) had 20% higher levels of 8-OHdG and 60% higher levels of Cu-Zn SOD compared to women with lower gravidity and parity (<4 pregnancies per lifetime). Our results present the first evidence for oxidative stress as a possible cost of reproductive effort in humans.

Dietary nitrate protects submandibular gland from hyposalivation in ovariectomized rats via suppressing cell apoptosis.

PubMed

Xu, Yipu; Pang, Baoxing; Hu, Liang; Feng, Xiaoyu; Hu, Lei; Wang, Jingsong; Zhang, Chunmei; Wang, Songlin

2018-02-26

Xerostomia, a major oral symptom of menopause, is a subjective feeling of dry mouth associated with oral pain and difficulties in deglutition and speech, which significantly reduces patient's quality of life. Dietary nitrate, which can be converted to nitric oxide, has multiple physiological functions in the body, including antioxidant activity and vasodilatation; however, its protective effect against xerostomia remains poorly understood. The present study aimed to evaluate the effects of dietary nitrate on estrogen deficiency-induced xerostomia. We established an ovariectomized (OVX) rat model, which included five groups: sham-operated, OVX, OVX + 0.4 mM nitrate, OVX + 2 mM nitrate, and OVX + 4 mM nitrate (n = 6). After ovariectomy, animals in the nitrate treatment groups received appropriate amounts of sodium nitrate dissolved in distilled water for 3 months. The results showed that nitrate treatment reduced body weight and water intake, and increased serum nitrate and nitrite levels. Furthermore, nitrate uptake increased saliva secretion as evidenced by saliva flow rates and aquaporin 5 expression, and alleviated histological lesions as evidenced by reduction of the fibrotic area and cell atrophy in the salivary glands. Although protective effects of nitrate against estrogen deficiency-induced xerostomia were observed at all doses, treatment with 2 mM nitrate was more effective than that with 0.4 mM and 4 mM nitrate. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 expression analyses showed that nitrate also protected cells from apoptosis, possibly through upregulation of Cu-Zn superoxide dismutase (Cu-Zn SOD) known to inhibit oxidative stress-related apoptosis. Our findings indicate that nitrate could improve functional activity of the salivary glands in OVX rats by suppressing apoptosis and upregulating Cu-Zn SOD expression, suggesting that dietary nitrate may potentially prevent hyposalivation in menopausal women. Copyright © 2018. Published by Elsevier Inc.

Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

PubMed

Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana

2014-08-01

Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups resulted in liver injury. These data suggest that clozapine appears to have a higher potential to induce liver toxicity than fluoxetine. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of zinc and influence of Acremonium lolii on growth parameters, chlorophyll a fluorescence and antioxidant enzyme activities of ryegrass (Lolium perenne L. cv Apollo).

PubMed

Bonnet, M; Camares, O; Veisseire, P

2000-05-01

The effects of zinc on growth, mineral content, chlorophyll a fluorescence, and detoxifying enzyme activity (ascorbate peroxidase (APX), EC 1.11.1.11; superoxide dismutase (SOD), EC 1.15.1.1) of ryegrass infected or not by Acremonium lolii, and treated with nutrient solution containing 0-50 mM ZnSO(4) were studied. The introduction of zinc induces stress with a decrease in growth at 1, 5 and 10 mM ZnSO(4) and a cessation of growth at 50 mM ZnSO(4), in ryegrass plants infected by A. lolii or not. This decrease in growth may be due to an accumulation of zinc in leaves. Nevertheless, symbiotic plants showed higher values in tiller number, an advantage conferred by the fungus. After 24 d of Zn exposure, leaf fresh weights and leaf water content were lower in plants growing with Zn in the culture medium and no advantage was conferred by the fungus to its host. An increase in Zn supply resulted in a decrease of the Ca, K, Mg, and Cu content of the leaves, a reduction in the quantum yield of electron flow throughout photosystem II (DeltaF/F(1)(m))and a lowering of the efficiency of photosynthetic energy conversion (F(v)/F(m)), compared to control plants. To counter this zinc stress, detoxifying enzymes APX and SOD increased (100%) when Zn reached the value of 50 mM in the nutrient solution. At 10 mM ZnSO(4), the presence of the fungus in the plant led to an increase in the threshold toxicity of plants to zinc by a diminution of APX activity.

A correlation of reactive oxygen species accumulation by depletion of superoxide dismutases with age-dependent impairment in the nervous system and muscles of Drosophila adults.

PubMed

Oka, Saori; Hirai, Jun; Yasukawa, Takashi; Nakahara, Yasuyuki; Inoue, Yoshihiro H

2015-08-01

The theory that accumulation of reactive oxygen species (ROS) in internal organs is a major promoter of aging has been considered negatively. However, it is still controversial whether overexpression of superoxide dismutases (SODs), which remove ROS, extends the lifespan in Drosophila adults. We examined whether ROS accumulation by depletion of Cu/Zn-SOD (SOD1) or Mn-SOD (SOD2) influenced age-related impairment of the nervous system and muscles in Drosophila. We confirmed the efficient depletion of Sod1 and Sod2 through RNAi and ROS accumulation by monitoring of ROS-inducible gene expression. Both RNAi flies displayed accelerated impairment of locomotor activity with age and shortened lifespan. Similarly, adults with nervous system-specific depletion of Sod1 or Sod2 also showed reduced lifespan. We then found an accelerated loss of dopaminergic neurons in the flies with suppressed SOD expression. A half-dose reduction of three pro-apoptotic genes resulted in a significant suppression of the neuronal loss, suggesting that apoptosis was involved in the neuronal loss caused by SOD silencing. In addition, depletion of Sod1 or Sod2 in musculature is also associated with enhancement of age-related locomotion impairment. In indirect flight muscles from SOD-depleted adults, abnormal protein aggregates containing poly-ubiquitin accumulated at an early adult stage and continued to increase as the flies aged. Most of these protein aggregates were observed between myofibril layers. Moreover, immuno-electron microscopy indicated that the aggregates were predominantly localized in damaged mitochondria. These findings suggest that muscular and neuronal ROS accumulation may have a significant effect on age-dependent impairment of the Drosophila adults.

MnSOD expression inhibited by electromagnetic pulse radiation in the rat testis.

PubMed

Zeng, LiHua; Ji, XiTuan; Zhang, YanJun; Miao, Xia; Zou, ChangXu; Lang, HaiYang; Zhang, Jie; Li, YuRong; Wang, XiaoWu; Qi, HongXing; Ren, DongQin; Guo, GuoZhen

2011-12-01

Male Sprague Dawley rats were exposed to EMP irradiation of 100 kV/m peak-to-peak e-field intensity and different numbers of pulses. Rat sperm samples were prepared for analysis of sperm qualities; Testes were assessed by transmission electron microscopy and serum hormone concentrations were examined by radioimmunoassay; Enzymatic activities of Total-superoxide dismutase(T-SOD) and manganese-superoxide dismutase (MnSOD), the mRNA levels of MnSOD and cuprozinc-superoxide dismutase (CuZnSOD), and the density of malondialdehyde (MDA) were also determined. EMP irradiation did not affect spermatozoon morphology, micronucleus formation rate, sperm number or viability, but the acrosin reaction rate decreased at 24 h and 48 h and recovered by 72 h after irradiation as compared to the controls. The ultrastructure of rat testis displayed more serious damage at 24 h than at other time points (6 h, 12 h, 48 h). Serum levels of luteotrophic hormone (LH) and testosterone (T) were elevated in irradiated rats as compared to controls. After irradiation, enzymatic activities of T-SOD and MnSOD were reduced by 24 h, consistent with the changes observed in MnSOD mRNA expression; MDA content increased at 6 h in turn. These studies have quantified the morphological damage and dysfunction in the rat reproductive system induced by EMP. The mechanism of EMP induced damage may be associated with the inhibition of MnSOD expression.

Protective effect of Mn(III)-desferrioxamine B upon oxidative stress caused by ozone and acid rain in the Brazilian soybean cultivar Glycine max "Sambaiba".

PubMed

Esposito, Jéssica Bordotti Nobre; Esposito, Breno Pannia; Azevedo, Ricardo Antunes; Cruz, Luciano Soares; da Silva, Luzimar Campos; de Souza, Silvia Ribeiro

2015-04-01

This study aimed to investigate the effects of the Mn complex (Mn(III)-desferrioxamine B (MnDFB)) on oxidative stress in the Brazilian soybean cultivar Glycine max "Sambaiba" following exposure to ozone and acid rain. We determined the suitable dose of MnDFB to apply to G. max seedlings using a dose-response curve. The highest superoxide dismutase (SOD) activity and Mn content in leaves were found upon the application of 8 μM MnDFB. Thus, G. max seedlings pretreated with 8 μM MnDFB were individually exposed to ozone and acid rain simulated. Pretreatment with MnDFB reduced lipid peroxidation upon ozone exposure and increased SOD activity in leaves; it did not alter the metal content in any part of the plant. Conversely, following acid rain exposure, neither the metal content in leaves nor SOD enzyme activity were directly affected by MnDFB, unlike pH. Our findings demonstrated that exogenous MnDFB application before ozone exposure may modulate the MnSOD, Cu/ZnSOD, and FeSOD activities to combat the ROS excess in the cell. Here, we demonstrated that the applied dose of MnDFB enhances antioxidative defenses in soybean following exposure to acid rain and especially to ozone.

Cellular Redox Systems Impact the Aggregation of Cu,Zn Superoxide Dismutase Linked to Familial Amyotrophic Lateral Sclerosis.

PubMed

Álvarez-Zaldiernas, Cristina; Lu, Jun; Zheng, Yujuan; Yang, Hongqian; Blasi, Juan; Solsona, Carles; Holmgren, Arne

2016-08-12

Protein misfolding is implicated in neurodegenerative diseases such as ALS, where mutations of superoxide dismutase 1 (SOD1) account for about 20% of the inherited mutations. Human SOD1 (hSOD1) contains four cysteines, including Cys(57) and Cys(146), which have been linked to protein stability and folding via forming a disulfide bond, and Cys(6) and Cys(111) as free thiols. But the roles of the cellular oxidation-reduction (redox) environment in SOD1 folding and aggregation are not well understood. Here we explore the effects of cellular redox systems on the aggregation of hSOD1 proteins. We found that the known hSOD1 mutations G93A and A4V increased the capability of the thioredoxin and glutaredoxin systems to reduce hSOD1 compared with wild-type hSOD1. Treatment with inhibitors of these redox systems resulted in an increase of hSOD1 aggregates in the cytoplasm of cells transfected with mutants but not in cells transfected with wild-type hSOD1 or those containing a secondary C111G mutation. This aggregation may be coupled to changes in the redox state of the G93A and A4V mutants upon mild oxidative stress. These results strongly suggest that the thioredoxin and glutaredoxin systems are the key regulators for hSOD1 aggregation and may play critical roles in the pathogenesis of ALS. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

[Oxidative Stress Level of Vanadium-exposed Workers].

PubMed

Wei, Teng-da; Li, Shun-pin; Liu, Yun-xing; Tan, Chun-ping; Li, Juan; Zhang, Zu-hui; Lan, Ya-jia; Zhang, Qin

2015-11-01

To determine the oxidative stress level in peripheral blood of vanadium-exposed workers, as an indication of population health effect of vanadium on human neurobehavioral system. 86 vanadium-exposed workers and 65 non-exposed workers were recruited by cluster sampling. A questionnaire was administered to collect demographic and occupational exposure information. Serum activity of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS) and malonaldehyde (MDA) contents were detected by kit assay. The differences in oxidative stress level between vanadium-exposed and non-exposed workers were compared. Vanadium-exposed workers had higher levels of MDA contents than the controls. The total superoxide dismutase(T-SOD) activity in vanadium-exposed workers was significantly lower than that in the controls, which was associated with lowered levels of manganese superoxide dismutase (Mn-SOD) activity. No changes in serum levels of cupro-zinc superoxide dismutase (CuZn-SOD) was found in vanadium-exposed workers. No difference in iNOS activity was found between vanadium-exposed workers and controls. Vanadium exposure increases free radical production in serum and reduces antioxidant capacity. But the relationship between vanadium exposure and iNOS damage remains uncertain.

1,25-Dihydroxyvitamin D3 and its analogues increase catalase at the mRNA, protein and activity level in a canine transitional carcinoma cell line.

PubMed

Middleton, R P; Nelson, R; Li, Q; Blanton, A; Labuda, J A; Vitt, J; Inpanbutr, N

2015-12-01

Antioxidant enzymes, such as catalase, superoxide dismutases (SOD), MnSOD and Cu/ZnSOD, protect cells by scavenging reactive oxygen species (ROS). Numerous studies have reported the anti-cancer effects of 1,25-dihydroxyvitamin D3 (calcitriol) and its related analogues, seocalcitol and analogue V. In this study, canine bladder transitional cell carcinoma (cbTCC) cells were used to determine effects of calcitriol and its related analogues on antioxidant enzyme gene expression, protein expression and activity. Catalase mRNA was increased in response to calcitriol (10(-7) M), and seocalcitol (10(-7) and 10(-9) M). MnSOD mRNA was decreased in response to calcitriol at 10(-7) M. Catalase was significantly increased in response to calcitriol (10(-7) and 10(-9) M), and seocalcitol (10(-9) M). Catalase enzymatic activity increased in response to calcitriol, seocalcitol and analogue V (10(-9) M). In addition, global gene expression analysis identified the involvement of mitogen-activated protein kinase (MAPK) signalling in cbTCC's response to calcitriol and seocalcitol treatment.

HoxB2 binds mutant SOD1 and is altered in transgenic model of ALS.

PubMed

Zhai, Jinbin; Lin, Hong; Canete-Soler, Rafaela; Schlaepfer, William W

2005-09-15

Mutations in Cu/Zn superoxide dismutase (SOD1) cause approximately 20% of familial amyotrophic lateral sclerosis by a toxic gain of function; however, the precise mechanisms remain unclear. Here, we report the identification of HoxB2, a homeodomain-containing transcription factor, as a G93A mutant SOD1 interactive protein in a yeast two-hybrid screen. We show that HoxB2 co-precipitates and co-localizes with mutant SOD1 in neuronal cell lines, as well as in brain and spinal cord of G93A mutant SOD1 transgenic mice. Mutagenesis further shows that this interaction is mediated by the central homeodomain of HoxB2. In motor neuron-like NSC-34 cells, overexpression of HoxB2 or its homeodomain decreases the insolubility of mutant SOD1 and inhibits G93A or G86R mutant SOD1-induced neuronal cell death. In human and mouse tissues, we show that expression of HoxB2 persists in adult spinal cord and is primarily localized in nuclei of motor neurons. In G93A transgenic mice, HoxB2 co-localizes with mutant SOD1 and is redistributed to perikarya and proximal neurites of motor neurons. In addition, there is progressive accumulation of HoxB2 and mutant SOD1 as punctate inclusions in the neuropil surrounding motor neurons. Taken together, our findings demonstrate that interaction of HoxB2 with mutant SOD1 occurs in motor neurons of G93A mutant SOD1 transgenic mice and suggest that this interaction may modulate the neurotoxicity of mutant SOD1.

Molecular characterization of a cDNA encoding copper/zinc superoxide dismutase from cultured cells of Manihot esculenta.

PubMed

Shin, Seung-Yong; Lee, Haeng-Soon; Kwon, Suk-Yoon; Kwon, Soon-Tae; Kwak, Sang-Soo

2005-01-01

Superoxide dismutase (SOD) cDNA, mSOD2, encoding cytosolic copper/zinc SOD (CuZnSOD) cDNA was isolated from suspension-cultured cells of cassava (Manihot esculenta Crantz) by cDNA library screening, and its expression was investigated in relation to environmental stress. mSOD2 is 774 bp in length with an open reading frame (ORF) of 152 amino acids, corresponding to a protein of predicted molecular mass 15 kDa and a pI of 5.22. One copy of the mSOD2 gene was found to be present in the cassava genome by Southern analysis using an mSOD2 cDNA-specific probe. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed diverse expression patterns for the mSOD2 gene in various tissues of intact cassava plants, at various stages of the growth in suspension cultures, and in the leaf tissues exposed to different stresses. The mSOD2 gene was highly expressed in suspension-cultured cells and in the stems of intact plants. However, it was expressed at low levels in leaves and roots. During suspension cell growth, the mSOD2 transcript progressively increased during culture. Moreover, the mSOD2 gene in excised cassava leaves responded to various stresses in different ways. In particular, it was highly induced in leaf tissue by several abiotic stresses, including high temperature (37 degrees C), chilling (4 degrees C), methyl viologen (MV) exposure, and wounding treatment. These results indicate that the mSOD2 gene is involved in the antioxidative process triggered by oxidative stress induced by environmental change.

ALS mutant SOD1 interacts with G3BP1 and affects stress granule dynamics.

PubMed

Gal, Jozsef; Kuang, Lisha; Barnett, Kelly R; Zhu, Brian Z; Shissler, Susannah C; Korotkov, Konstantin V; Hayward, Lawrence J; Kasarskis, Edward J; Zhu, Haining

2016-10-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Mutations in Cu/Zn superoxide dismutase (SOD1) are responsible for approximately 20 % of the familial ALS cases. ALS-causing SOD1 mutants display a gain-of-toxicity phenotype, but the nature of this toxicity is still not fully understood. The Ras GTPase-activating protein-binding protein G3BP1 plays a critical role in stress granule dynamics. Alterations in the dynamics of stress granules have been reported in several other forms of ALS unrelated to SOD1. To our surprise, the mutant G93A SOD1 transgenic mice exhibited pathological cytoplasmic inclusions that co-localized with G3BP1-positive granules in spinal cord motor neurons. The co-localization was also observed in fibroblast cells derived from familial ALS patient carrying SOD1 mutation L144F. Mutant SOD1, unlike wild-type SOD1, interacted with G3BP1 in an RNA-independent manner. Moreover, the interaction is specific for G3BP1 since mutant SOD1 showed little interaction with four other RNA-binding proteins implicated in ALS. The RNA-binding RRM domain of G3BP1 and two particular phenylalanine residues (F380 and F382) are critical for this interaction. Mutant SOD1 delayed the formation of G3BP1- and TIA1-positive stress granules in response to hyperosmolar shock and arsenite treatment in N2A cells. In summary, the aberrant mutant SOD1-G3BP1 interaction affects stress granule dynamics, suggesting a potential link between pathogenic SOD1 mutations and RNA metabolism alterations in ALS.

Implications of fALS Mutations on Sod1 Function and Oligomerization in Cell Models.

PubMed

Brasil, Aline A; Magalhães, Rayne S S; De Carvalho, Mariana D C; Paiva, Isabel; Gerhardt, Ellen; Pereira, Marcos D; Outeiro, Tiago F; Eleutherio, Elis C A

2018-06-01

Among the familial forms of amyotrophic lateral sclerosis (fALS), 20% are associated with the Cu,Zn-superoxide dismutase (Sod1). fALS is characterized by the accumulation of aggregated proteins and the increase in oxidative stress markers. Here, we used the non-invasive bimolecular fluorescence complementation (BiFC) assay in human H4 cells to investigate the kinetics of aggregation and subcellular localization of Sod1 mutants. We also studied the effect of the different Sod1 mutants to respond against oxidative stress by following the levels of reactive oxygen species (ROS) after treatment with hydrogen peroxide. Our results showed that only 30% of cells transfected with A4VSod1 showed no inclusions while for the other Sod1 mutants tested (L38V, G93A and G93C), this percentage was at least 70%. In addition, we found that 10% of cells transfected with A4VSod1 displayed more than five inclusions per cell and that A4V and G93A Sod1 formed inclusions more rapidly than L38V and G93C Sod1. Expression of WTSod1 significantly decreased the intracellular oxidation levels in comparison with expression of fALS Sod1 mutants, suggesting the mutations induce a functional impairment. All fALS mutations impaired nuclear localization of Sod1, which is important for maintaining genomic stability. Consistently, expression of WTSod1, but not of fALS Sod1 mutants, reduced DNA damage, as measured by the comet assay. Altogether, our study sheds light into the effects of fALS Sod1 mutations on inclusion formation, dynamics, and localization as well as on antioxidant response, opening novel avenues for investigating the role of fALS Sod1 mutations in pathogenesis.

Cloning and characterization of iron-superoxide dismutase in Antarctic yeast strain Rhodotorula mucilaginosa AN5.

PubMed

Kan, Guangfeng; Wen, Hua; Wang, Xiaofei; Zhou, Ting; Shi, Cuijuan

2017-08-01

A novel superoxide dismutase gene from Antarctic yeast Rhodotorula mucilaginosa AN5 was cloned, sequenced, and then expressed in Escherichia coli. The R. mucilaginosa AN5 SOD (RmFeSOD) gene was 639 bp open reading frame in length, which encoded a protein of 212 amino acids with a deduced molecular mass of 23.5 kDa and a pI of 7.89. RmFeSOD was identified as iron SOD type with a natural status of homodimer. The recombinant RmFeSOD showed good pH stability in the pH 1.0-9.0 after 1 h incubation. Meanwhile, it was found to behave relatively high thermostability, and maintained more than 80% activity at 50 °C for 1 h. By addition of 1 mM metal ions, the enzyme activity increased by Zn 2+ , Cu 2+ , Mn 2+ , and Fe 3+ , and inhibited only by Mg 2+ . RmFeSOD showed relatively low tolerance to some compounds, such as PMSF, SDS, Tween-80, Triton X-100, DMSO, β-ME, and urea. However, DTT showed no inhibition to enzyme activity. Using copper stress experiment, the RmFeSOD recombinant E. coli exhibited better growth than non-recombinant bacteria, which revealed that RmFeSOD might play an important role in the adaptability of heavy metals. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Agar, Jeffrey N; Taylor, David M; Minotti, Sandra; Durham, Heather D

2004-06-01

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a familial form of amyotrophic lateral sclerosis (fALS). The present study demonstrated impaired proteasomal function in the lumbar spinal cord of transgenic mice expressing human SOD-1 with the ALS-causing mutation G93A (SOD-1(G93A)) compared to non-transgenic littermates (LM) and SOD-1(WT) transgenic mice. Chymotrypsin-like activity was decreased as early as 45 days of age. By 75 days, chymotrypsin-, trypsin-, and caspase-like activities of the proteasome were impaired, at about 50% of control activity in lumbar spinal cord, but unchanged in thoracic spinal cord and liver. Both total and specific activities of the proteasome were reduced to a similar extent, indicating that a change in proteasome function, rather than a decrease in proteasome levels, had occurred. Similar decreases of total and specific activities of the proteasome were observed in NIH 3T3 cell lines expressing fALS mutants SOD-1(G93A) and SOD-1(G41S), but not in SOD-1(WT) controls. Although overall levels of proteasome were maintained in spinal cord of SOD-1(G93A) transgenic mice, the level of 20S proteasome was substantially reduced in lumbar spinal motor neurons relative to the surrounding neuropil. It is concluded that impairment of the proteasome is an early event and contributes to ALS pathogenesis.

High mortality rates occur in copper deficient rats exposed to a normally nonlethal endotoxin treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

DiSilvestro, R.; Joseph, E.; Yang, F.L.

Endotoxin hepatotoxicity is proposed to occur by processes which could be retarded by 3 copper enzymes: ceruloplasmin, Cu-Zn superoxide dismutase (SOD), and extracellular (EC) SOD. Weanling rats fed low copper for 40 days showed low activity levels of these enzymes, and a very high mortality rate 20 h after endotoxin injection. No rats fed adequate copper died from this treatment. In addition, serum transaminase activities, indicators of liver damage, were elevated by 3 h to a greater extent in the deficient rats than in the adequates. The high susceptibility to endotoxemia in the deficient rats was not associated with lowmore » hepatic glutathione, high liver malondialedhyde, nor restricted metallothionein induction 3 h after endotoxin injection. Endotoxin reduced serum EC SOD activities in adequate and deficient rats, but final values were lower in the latter. Studies on roles of specific copper enzymes in resistance to endotoxemia are currently underway.« less

Characterization of antioxidant enzymes and peroxisomes of olive (Olea europaea L.) fruits.

PubMed

Lopez-Huertas, Eduardo; del Río, Luis A

2014-10-15

The presence of peroxisomes in olive (Olea europaea L.) fruits and different antioxidant enzymes occurring in this plant tissue is reported for the first time. Ultrastructural analysis showed that olive cells were characterized by the presence of large vacuoles and lipid drops. Plastids, mitochondria and peroxisomes were placed near the cell wall, showing some type of association with it. Olive fruit peroxisomes were purified by sucrose density-gradient centrifugation, and catalase, glutathione reductase and ascorbate peroxidase were found in peroxisomes. In olive fruit tissue the presence of a battery of antioxidant enzymes was demonstrated, including catalase, four superoxide dismutase isozymes (mainly an Fe-SOD plus 2 Cu,Zn-SOD and a Mn-SOD), all the enzymes of the ascorbate-glutathione cycle, reduced and oxidized glutathione, ascorbate, and four NADPH-recycling dehydrogenases. The knowledge of the full composition of antioxidants (enzymatic and non-enzymatic) in olive fruits is crucial to be able to understand the processes regulating the antioxidant composition of olive oil. Copyright © 2014 Elsevier GmbH. All rights reserved.

Effect of dietary manganese on antioxidant status and expression levels of heat-shock proteins and factors in tissues of laying broiler breeders under normal and high environmental temperatures.

PubMed

Zhu, Yong-Wen; Lu, Lin; Li, Wen-Xiang; Zhang, Li-Yang; Ji, Cheng; Lin, Xi; Liu, Hsiao-Ching; Odle, Jack; Luo, Xu-Gang

2015-12-28

To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (sem 1)°C and high, 32 (sem 1)°C)×3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase of malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.

INCREASED RENAL OXIDATIVE STRESS IN SALT-SENSITIVE HUMAN GRK4γ486V TRANSGENIC MICE

PubMed Central

Diao, Zhenyu; Asico, Laureano D.; Villar, Van Anthony M.; Zheng, Xiaoxu; Cuevas, Santiago; Armando, Ines; Jose, Pedro A.; Wang, Xiaoyan

2017-01-01

We tested the hypothesis that salt-sensitive hypertension is caused by renal oxidative stress by measuring the blood pressure and reactive oxygen species-related proteins in the kidneys of human G protein-coupled receptor kinase 4γ (hGRK4γ) 486V transgenic mice and non-transgenic (Non-T) littermates on normal and high salt diets. High salt diet increased the blood pressure, associated with impaired sodium excretion, in hGRK4γ486V mice. Renal expressions of NOX isoforms were similar in both strains on normal salt diet but NOX2 was decreased by high salt diet to a greater extent in Non-T than hGRK4γ486V mice. Renal HO-2, but not HO-1, protein was greater in hGRK4γ486V than Non-T mice on normal salt diet and normalized by high salt diet. On normal salt diet, renal CuZnSOD and ECSOD proteins were similar but renal MnSOD was lower in hGRK4γ486V than Non-T mice and remained low on high salt diet. High salt diet decreased renal CuZnSOD in hGRK4γ486V but not Non-T mice and decreased renal ECSOD to a greater extent in hGRK4γ486V than Non-T mice. Renal SOD activity, superoxide production, and NOS3 protein were similar in two strains on normal salt diet. However, high salt diet decreased SOD activity and NOS3 protein and increased superoxide production in hGRK4γ486V mice but not in Non-T mice. High salt diet also increased urinary 8-isoprostane and 8-hydroxydeoxyguanosine to a greater extent in hGRK4γ486V than Non-T mice. hGRK4γwild-type mice were normotensive and hGRK4γ142V mice were hypertensive but both were salt-resistant and in normal redox balance. Chronic tempol treatment partially prevented the salt-sensitivity of hGRK4γ486V mice. Thus, hGRK4γ486V causes salt-sensitive hypertension due, in part, to defective renal antioxidant mechanisms. PMID:28189851

Transcription regulation of gene expression in rat brown adipose tissue in response to unloading or 2G loading during growing period

NASA Astrophysics Data System (ADS)

Watanabe, S.; Hitomi, Y.; Kawano, F.; Ohira, Y.; Kizaki, T.; Nakano, N.; Sakurai, T.; Izawa, T.; Suzuki, K.; Sudoh, M.; Roy, R. R.; Ohno, H.

2007-05-01

The effects were investigated of long-term unloading and macrogravity on the expression of 15 genes at the mRNA levels in brown adipose tissue (BAT) from rat pups, particularly focusing on uncoupling protein (UCP) family, nitric oxide synthase (NOS) isoenzymes, and antioxidant enzymes. The animals in the unloaded group (a simulation model of spaceflight) were hindlimb-unloaded by tail suspension between postnatal day 4 and month 3, followed by 2-mo ambulation recovery. Moreover, centrifugation at 2G (an imitation of the hypergravity effects) was performed during the same period as the unloading, also followed by 2-mo ambulation recovery (adaptation to 1G from 2G). Compared with the age-matched control group, significantly lower expression levels of mRNA for UCP2, iNOS, and Cu,Zn-superoxide dismutase (Cu, Zn-SOD) in BAT were observed immediately after unloading, but not immediately after exposure to 2G. During 2-mo ambulation recovery from both extreme conditions, the expression of mRNA for Mn-SOD was enhanced, suggesting an increase in oxidative stress. These findings suggest that both micro- and macrogravity may have some influence upon the function of BAT, and that changes in the BAT function may be involved in the mechanisms subserving adaptation to such extreme conditions by what humans have to be faced with during the spaceflight and return to 1G.

Antioxidant Expression Response to Free Radicals in Active Men and Women Fallowing to a Session Incremental Exercise; Numerical Relationship Between Antioxidants and Free Radicals.

PubMed

Baghaiee, Behrouz; Aliparasti, Mohammad Reza; Almasi, Shohreh; Siahkuhian, Marefat; Baradaran, Behzad

2016-06-01

Energy production is a necessary process to continue physical activities, and exercise is associated with more oxygen consumption and increase of oxidative stress. what seems important is the numerical relationship between antioxidant and free radicals. Although the activity of some enzymes increases with physical activities, but it is possible that gene expression of this enzyme is not changed during exercise. The aim of the present study is to investigate the antioxidant enzymes gene expression and changes in malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in men and women affected by a session of incremental exercise and to carefully and numerically assess the relationship between MDA changes and gene expression and activity of antioxidant enzymes. 12 active men and 12 active women (21 - 24 years old) participated voluntarily in this study. Peripheral blood samples were taken from the subjects in three phases, before and after graduated exercise test (GXT) and 3 hours later (recovery). The gene expression of manganese superoxide dismutase (MnSOD) enzyme increased significantly in women in the recovery phase (P < 0.05). Catalase gene expression significantly increased in men in both phases (immediately & recovery) (P < 0.05). But the changes in active women were only significant immediately after the exercise. TAC levels increased significantly in men in the recovery phase and in active women immediately after the exercise (P < 0.05). MDA activity also increased significantly in men in both phases (P < 0.05). However, in women the increase was significant only in the recovery phase (P < 0.05). There was a reverse relationship between changes in MnSOD and copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) levels and MDA in men (P < 0.05). In active women there was also a significant relationship between changes in MDA and gene expression of Cu/ZnSOD and TAC (P < 0.05). The increase in free radicals during incremental exercises challenges gene expression and activity of antioxidant enzymes. However, despite the negative effects of free radicals, in women, activity and gene expression of antioxidant enzymes respond appropriately to free radicals.

Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wei, E-mail: weiwang2@illinois.edu; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbasava2@illinois.edu

2012-01-15

Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 31–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100 μg/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1 mM).more » During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1 mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10 μg/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5 mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. -- Highlights: ► DEHP inhibits growth and increases reactive oxygen species in ovarian antral follicles in vitro. ► NAC rescues the effects of DEHP on the growth and reactive oxygen species levels in follicles. ► DEHP decreases the expression and activity of Cu/Zn superoxide dismutase, which can be rescued by NAC, in antral follicles.« less

CTT1 overexpression increases life span of calorie-restricted Saccharomyces cerevisiae deficient in Sod1.

PubMed

Rona, Germana; Herdeiro, Ricardo; Mathias, Cristiane Juliano; Torres, Fernando Araripe; Pereira, Marcos Dias; Eleutherio, Elis

2015-06-01

Studies using different organisms revealed that reducing calorie intake, without malnutrition, known as calorie restriction (CR), increases life span, but its mechanism is still unkown. Using the yeast Saccharomyces cerevisiae as eukaryotic model, we observed that Cu, Zn-superoxide dismutase (Sod1p) is required to increase longevity, as well as to confer protection against lipid and protein oxidation under CR. Old cells of sod1 strain also presented a premature induction of apoptosis. However, when CTT1 (which codes for cytosolic catalase) was overexpressed, sod1 and WT strains showed similar survival rates. Furthermore, CTT1 overexpression decreased lipid peroxidation and delayed the induction of apoptotic process. Superoxide is rapidly converted to hydrogen peroxide by superoxide dismutase, but it also undergoes spontaneous dismutation albeit at a slower rate. However, the quantity of peroxide produced from superoxide in this way is two-fold higher. Peroxide degradation, catalyzed by catalase, is of vital importance, because in the presence of a reducer transition metal peroxide is reduced to the highly reactive hydroxyl radical, which reacts indiscriminately with most cellular constituents. These findings might explain why overexpression of catalase was able to overcome the deficiency of Sod1p, increasing life span in response to CR.

The molecular mechanism of the termination of insect diapause, part 1: A timer protein, TIME-EA4, in the diapause eggs of the silkworm Bombyx mori is a metallo-glycoprotein.

PubMed

Isobe, Minoru; Kai, Hidenori; Kurahashi, Takuya; Suwan, Sathorn; Pitchayawasin-Thapphasaraphong, Suthasinee; Franz, Thomas; Tani, Naoki; Higashi, Kenichiro; Nishida, Hideo

2006-10-01

TIME-EA4 is an ATPase that measures time intervals, functioning as a diapause duration clock in diapause eggs of the silkworm, Bombyx mori. Characterization of the primary and higher structures of the TIME-EA4 would be desirable to clarify the mechanism by which the protein measures the time intervals. In our current studies, the whole sequence of TIME-EA4 has been established as that of a metallo-glycoprotein by combinational means involving peptide sequence analysis, nano-HPLC-ESI-Q-TOF-MS and MS/MS, and cDNA dictation. The amino acid sequence of TIME-EA4 showed 46-55 % homology with the reported proteins of the Cu,Zn-SOD (superoxide dismutase) family; in particular, the SOD active site (core domain) includes metal-binding amino acid ligands and a disulfide bond, and these structures are completely identical in Bombyx SOD, bovine SOD, and TIME-EA4 proteins. We found, however, that TIME-EA4 contains one more copper ion than other SODs, as was proven under neutral nondenaturing conditions. ESI mass spectrometry revealed that the timer function was not in the SOD core domain. In addition, TIME-EA4 has an attached sugar chain, which is indispensable to its functioning as a timer protein.

RNA interference-mediated silencing of mutant superoxide dismutase rescues cyclosporin A-induced death in cultured neuroblastoma cells

PubMed Central

Maxwell, Michele M.; Pasinelli, Piera; Kazantsev, Aleksey G.; Brown, Robert H.

2004-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder resulting from selective death of motor neurons in the brain and spinal cord. In ≈25% of familial ALS cases, the disease is caused by dominantly acting point mutations in the gene encoding cytosolic Cu,Zn superoxide dismutase (SOD1). In cell culture and in rodent models of ALS, mutant SOD1 proteins exhibit dose-dependent toxicity; thus, agents that reduce mutant protein expression would be powerful therapeutic tools. A wealth of recent evidence has demonstrated that the mechanism of RNA-mediated interference (RNAi) can be exploited to achieve potent and specific gene silencing in vitro and in vivo. We have evaluated the utility of RNAi for selective silencing of mutant SOD1 expression in cultured cells and have identified small interfering RNAs capable of specifically inhibiting expression of ALS-linked mutant, but not wild-type, SOD1. We have investigated the functional effects of RNAi-mediated silencing of mutant SOD1 in cultured murine neuroblastoma cells. In this model, stable expression of mutant, but not wild-type, human SOD1 sensitizes cells to cytotoxic stimuli. We find that silencing of mutant SOD1 protects these cells against cyclosporin A-induced cell death. These results demonstrate a positive physiological effect caused by RNAi-mediated silencing of a dominant disease allele. The present study further supports the therapeutic potential of RNAi-based methods for the treatment of inherited human diseases, including ALS. PMID:14981234

Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium.

PubMed

Rush, James W E; Turk, James R; Laughlin, M Harold

2003-04-01

Vascular oxidative stress contributes to endothelial dysfunction. Aerobic exercise training improves vascular function. The purpose of this study was to test the hypothesis that exercise training would improve the balance of antioxidant to prooxidant enzymes and reduce markers of oxidative stress in aortic endothelial cells (AEC). Female Yucatan miniature pigs either remained sedentary (SED) or were exercise trained (EX) for 16-19 wk. EX pigs had increased AEC SOD-1 protein levels and Cu/Zn SOD activity of the whole aorta compared with SED pigs. Protein levels of other antioxidant enzymes (SOD-2, catalase) were not affected by exercise training. Protein levels of p67(phox), a subunit of the prooxidant enzyme NAD(P)H oxidase, were reduced in EX vs. SED AEC. These EX adaptations were associated with lower AEC malondialdehyde levels and decreased phosphorylation of ERK-1/2. Endothelial nitric oxide synthase protein, protein nitrotyrosine content, and heme oxygenase-1 protein were not different in EX vs. SED pigs. We conclude that chronic aerobic exercise training influenced both antioxidant and prooxidant enzymes and decreased indexes of oxidative stress in AEC. These adaptations may contribute to improved endothelial function with exercise training.

Imidazole-containing phthalazine derivatives inhibit Fe-SOD performance in Leishmania species and are active in vitro against visceral and mucosal leishmaniasis.

PubMed

Sánchez-Moreno, M; Gómez-Contreras, F; Navarro, P; Marín, C; Ramírez-Macías, I; Rosales, M J; Campayo, L; Cano, C; Sanz, A M; Yunta, M J R

2015-07-01

The in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1-4 was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, and their cytotoxicity on J774·2 macrophage cells was also measured. All compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the three Leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their bisalkylamino substituted counterparts 1 and 3. Both infection rate measures and ultrastructural alterations studies confirmed that 2 and 4 were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with 2 and 4 were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds 2 and 4 were potent inhibitors of iron superoxide dismutase enzyme (Fe-SOD) in the three species considered, whereas their impact on human CuZn-SOD was low. Molecular modelling suggests that 2 and 4 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the antioxidant features of the enzyme.

Trace elements profile is associated with insulin resistance syndrome and oxidative damage in thyroid disorders: Manganese and selenium interest in Algerian participants with dysthyroidism.

PubMed

Maouche, Naima; Meskine, Djamila; Alamir, Barkahoum; Koceir, Elhadj-Ahmed

2015-10-01

The relationship between dysthyroidism and antioxidant trace elements (ATE) status is very subtle during oxidative stress (OS). This relationship is mediated by thyroid hormone (TH) disorder, insulin resistance syndrome (IRS) and inflammation. The aim of this study was to investigate ATE such as selenium (Se), manganese (Mn), zinc (Zn) and copper (Cu) status on thyroid dysfunction, and their interaction with antioxidant enzyme activities, mainly, superoxide dismutase (SOD) and glutathione peroxidase (GPx), TH profile (TSH, T(3), T(4)) and IRS clusters. The study was undertaken on 220 Algerian adults (30-50 years), including 157 women and 63 men who were divided to 4 groups: subclinical hypothyroidism (n = 50), overt hypothyroidism (n = 60), Graves's disease hyperthyroidism (n = 60) and euthyroid controls (n = 50). The IRS was confirmed according to NCEP (National Cholesterol Education Program). Insulin resistance was evaluated by HOMA-IR model. Trace elements were determined by the Flame Atomic Absorption Spectrometry (Flame-AAS) technique. The antioxidant enzymes activity and metabolic parameters were determined by biochemical methods. The TH profile and anti-Thyroperoxidase Antibodies (anti-TPO-Ab) were evaluated by radioimmunoassay. Results showed that the plasma manganese levels were significantly increased in all dysthyroidism groups (p ≤ 0.01). However, the plasma copper and zinc concentrations were maintained normal or not very disturbed vs control group. In contrast, the plasma selenium levels were highly decreased (p ≤ 0.001) and positively correlated with depletion of glutathione peroxidase activity; and associated both with anti-TPO-Ab overexpression and fulminant HS-CRP levels. This study confirms the oxidative stress-inflammation relationship in the dysthyroidism. The thyroid follicles antioxidant protection appears preserved in the cytosol (Cu/Zn-SOD), while it is altered in the mitochondria (Mn-SOD), which gives this cell organelle, a status of real target therapy in thyroid dysfunction. The publisher would like to apologise for any inconvenience caused. [corrected].

Enhanced Detection of Sub-Retinal Pigment Epithelial Cell Layer Deposits in Human and Murine Tissue: Imaging Zinc as a Biomarker for Age-Related Macular Degeneration (An American Ophthalmological Society Thesis)

PubMed Central

van Kuijk, Frederik J.G.M.; McPherson, Scott W.; Roehrich, Heidi

2017-01-01

Purpose Understanding the apparent paradoxical role of zinc in the pathogenesis and prevention of age-related macular degeneration (AMD) has been limited by the lack of animal models for its detection in sub-retinal epithelial deposits (drusen), a definitive early hallmark of AMD. In-vitro studies using Zinpyr-1 showed drusen contained high levels of zinc, but the probe was not suitable for in-vivo studies. This study compares Zinpyr-1 to ZPP1, a new fluorescein-based probe for zinc, to assess the potential of ZPP1 for in-vivo detection of zinc in drusen. Methods Flat mounts of human sub-RPE tissue using the probes were analyzed by fluorescence and confocal microscopy. Flat mounts of sub-RPE tissue from mice deficient in superoxide dismutase isoform-1 (CuZn-SOD-KO) or isoform-2 (Mn-SOD-RPE-KO) were analyzed with sub-RPE deposits confirmed by histology. Results Drusen are detected in greater numbers and intensity with ZPP1 compared to Zinpyr-1. Using ZPP1, drusen was detected in a sample from a 46-year old human donor without ocular history, suggesting that ZPP1 might be sensitive enough to detect drusen at an early stage. With CuZn-SOD KO mice, ZPP1 detected sub-RPE deposits at 10 months of age, whereas Zinpyr-1 required 14 months. Conclusion Detection of sub-RPE deposits by ZPP1 was greatly enhanced compared to Zinpyr-1. This enhanced sensitivity will allow for more insightful analysis of zinc in AMD using human specimens and mouse models. This could result in the development of a sensitive in-vivo probe to enhance research on the role zinc in drusen formation and the early clinical diagnosis of AMD. PMID:29021717

Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes.

PubMed

Penkowa, M; Giralt, M; Thomsen, P S; Carrasco, J; Hidalgo, J

2001-04-01

The role of zinc- and copper-deficient diets on the inflammatory response to traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc deficiency decreased food intake and body weight gain, and the latter effect was higher than that observed in pair-fed rats. In noninjured brains, zinc deficiency only affected significantly lectin (increasing) and glial fibrillary acidic protein (GFAP) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (decreasing) immunoreactivities (irs). In injured brains, a profound gliosis was observed in the area surrounding the lesion, along with severe damage to neurons as indicated by neuron specific enolase (NSE) ir, and the number of cells undergoing apoptosis (measured by TUNEL) was dramatically increased. Zinc deficiency significantly altered brain response to TBI, potentiating the microgliosis and reducing the astrogliosis, while increasing the number of apoptotic cells. Metallothioneins (MTs) are important zinc- and copper-binding proteins in the CNS, which could influence significantly the brain response to TBI because of their putative roles in metal homeostasis and antioxidant defenses. MT-I+II expression was dramatically increased by TBI, and this response was significantly blunted by zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc deficiency. TBI strongly increased oxidative stress levels, as demonstrated by malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor kappaB (NF-kappaB) levels irs, all of which were potentiated by zinc deficiency. Further analysis revealed unbalanced expression of prooxidant and antioxidant proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS) and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All these effects were attributable to zinc deficiency, since pair-fed rats did not differ from normally fed rats. In general, copper deficiency caused a similar pattern of responses, albeit more moderate. Results obtained in mice with a null mutation for the MT-I+II isoforms strongly suggest that most of the effects observed in the rat brain after zinc and copper deficiencies are attributable to the concomitant changes in the MT expression.

Comparative expression analysis of immune-related factors in the sea cucumber Apostichopus japonicus.

PubMed

Jiang, Jingwei; Zhou, Zunchun; Dong, Ying; Zhao, Zelong; Sun, Hongjuan; Wang, Bai; Jiang, Bei; Chen, Zhong; Gao, Shan

2018-01-01

In order to preliminarily explore the joint involvement of different immune-related factors during the same immune process in Apostichopus japonicus, the transcriptional expression of Cu/Zn superoxide dismutase (Cu/Zn-SOD), catalase (CAT), c-type lysozyme (c-LYZ), i-type lysozyme (i-LYZ), cathepsin D, melanotransferrin (MTF), Toll, c-type lectin (c-LCT) and complement 3 (C3) during the development from fertilized eggs to juveniles and after challenging the juveniles with Vibrio splendidus, Pseudoalteromonas nigrifaciens, Shewanella baltica and Bacillus cereus, respectively, was measured using the method of quantitative real-time PCR (qRT-PCR), and then the correlations among different immune-related factors were analyzed. The results showed that the selected immune-related factors were expressed at all of the determined developmental stages and significantly up-regulated at doliolaria stage, suggesting the selected factors are indispensable immune components and the immune system might be broadly activated at doliolaria stage in A. japonicus. After challenged with four pathogenic bacteria, Cu/Zn-SOD, CAT, i-LYZ, cathepsin D, MTF, Toll, C3 were all significantly down-regulated at 4 h, indicating that some components of A. japonicus immune system might be inhibited at the beginning of pathogenic bacteria invasion. The immune-responsive analysis also showed that the significant regulation in Toll after challenged with four tested bacteria, that in MTF after challenged with S. baltica and that in C3 after challenged with P. nigrifaciens were all minus, suggesting Toll, MTF and C3 are probably the primary targets of pathogenic bacteria attack. Furthermore, the correlation analysis indicated that, all of the selected immune-related factors except cathepsin D might be in the same immune regulatory network during A. japonicus development, while all of the selected immune-related factors except c-LYZ might be in the same responsive regulatory network after challenged with four pathogenic bacteria. Altogether, A. japonicus immune system exhibited high complexity in regulation during organism development and after bacterial challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Copper/zinc superoxide dismutase insufficiency impairs progesterone secretion and fertility in female mice.

PubMed

Noda, Yoshihiro; Ota, Kuniaki; Shirasawa, Takuji; Shimizu, Takahiko

2012-01-01

Copper/zinc superoxide dismutase (CuZn-SOD, SOD1) is one of the major antioxidant enzymes, and is localized in the cytoplasm to scavenge superoxide. To investigate the physiological role of SOD1 in the ovaries, we analyzed the fertility of Sod1-deficient female mice. To evaluate their hormonal metabolism, we measured pituitary and ovarian hormone levels in the plasma of the mutant mice. Plasma follicle-stimulating hormone, luteinizing hormone, and estradiol were not altered in the mutant compared to the wild-type females, while the plasma progesterone level was significantly reduced in the mutant females. Furthermore, the mutant mice showed decreased progesterone secretion under the condition of superovulation. In a histochemical analysis, we observed a remarkable reduction in the corpus luteum area in the mutant ovaries without atrophic changes. The mutant mice also displayed enhanced superoxide generation in the region surrounding the corpora lutea, which was associated with increased apoptotic cells and suppressed vasculature. These results suggested that SOD1 deficiency dysregulated luteal formation because of increased superoxide generation in the ovary. In vitro fertilization experiments showed no abnormal fertilization of Sod1-deficient oocytes. In addition, when Sod1-deficient embryos were transferred into the oviducts of wild-type females, mutant embryos developed at a normal rate, indicating that SOD1 deficiency in embryos did not cause miscarriage in the uterus of wild-type females. These results indicated that increased intracellular ROS impaired luteal formation and progesterone production in the mutant females, thus suggesting that SOD1 plays a crucial role in both the luteal function and the maintenance of fertility in female mice.

Mitochondrial dynamics and bioenergetic dysfunction is associated with synaptic alterations in mutant SOD1 motor neurons

PubMed Central

Magrané, Jordi; Sahawneh, Mary Anne; Przedborski, Serge; Estévez, Álvaro G.; Manfredi, Giovanni

2012-01-01

Mutations in Cu,Zn superoxide dismutase (SOD1) cause familial amyotrophic lateral sclerosis (FALS), a rapidly fatal motor neuron disease. Mutant SOD1 has pleiotropic toxic effects on motor neurons, among which mitochondrial dysfunction has been proposed as one of the contributing factors in motor neuron demise. Mitochondria are highly dynamic in neurons; they are constantly reshaped by fusion and move along neurites to localize at sites of high-energy utilization, such as synapses. The finding of abnormal mitochondria accumulation in neuromuscular junctions, where the SOD1-FALS degenerative process is though to initiate, suggests that impaired mitochondrial dynamics in motor neurons may be involved in pathogenesis. We addressed this hypothesis by live imaging microscopy of photo-switchable fluorescent mitoDendra in transgenic rat motor neurons expressing mutant or wild type human SOD1. We demonstrate that mutant SOD1 motor neurons have impaired mitochondrial fusion in axons and cell bodies. Mitochondria also display selective impairment of retrograde axonal transport, with reduced frequency and velocity of movements. Fusion and transport defects are associated with smaller mitochondrial size, decreased mitochondrial density, and defective mitochondrial membrane potential. Furthermore, mislocalization of mitochondria at synapses among motor neurons, in vitro, correlates with abnormal synaptic number, structure, and function. Dynamics abnormalities are specific to mutant SOD1 motor neuron mitochondria, since they are absent in wild type SOD1 motor neurons, they do not involve other organelles, and they are not found in cortical neurons. Taken together, these results suggest that impaired mitochondrial dynamics may contribute to the selective degeneration of motor neurons in SOD1-FALS. PMID:22219285

Palladium and Platinum Nanoparticles Attenuate Aging-Like Skin Atrophy via Antioxidant Activity in Mice

PubMed Central

Shibuya, Shuichi; Ozawa, Yusuke; Watanabe, Kenji; Izuo, Naotaka; Toda, Toshihiko; Yokote, Koutaro; Shimizu, Takahiko

2014-01-01

Cu-Zn superoxide dismutase (Sod1) loss causes a redox imbalance as it leads to excess superoxide generation, which results in the appearance of various aging-related phenotypes, including skin atrophy. Noble metal nanoparticles, such as palladium (Pd) and platinum (Pt) nanoparticles, are considered to function as antioxidants due to their strong catalytic activity. In Japan, a mixture of Pd and Pt nanoparticles called PAPLAL has been used to treat chronic diseases over the past 60 years. In the present study, we investigated the protective effects of PAPLAL against aging-related skin pathologies in mice. Transdermal PAPLAL treatment reversed skin thinning associated with increased lipid peroxidation in Sod1 −/− mice. Furthermore, PAPLAL normalized the gene expression levels of Col1a1, Mmp2, Has2, Tnf-α, Il-6, and p53 in the skin of the Sod1 −/− mice. Pt nanoparticles exhibited marked SOD and catalase activity, while Pd nanoparticles only displayed weak SOD and catalase activity in vitro. Although the SOD and catalase activity of the Pt nanoparticles significantly declined after they had been oxidized in air, a mixture of Pd and Pt nanoparticles continued to exhibit SOD and catalase activity after oxidation. Importantly, a mixture of Pd and Pt nanoparticles with a molar ratio of 3 or 4 to 1 continued to exhibit SOD and catalase activity after oxidation, indicating that Pd nanoparticles prevent the oxidative deterioration of Pt nanoparticles. These findings indicate that PAPLAL stably suppresses intrinsic superoxide generation both in vivo and in vitro via SOD and catalase activity. PAPLAL is a potentially powerful tool for the treatment of aging-related skin diseases caused by oxidative damage. PMID:25333617

Palladium and platinum nanoparticles attenuate aging-like skin atrophy via antioxidant activity in mice.

PubMed

Shibuya, Shuichi; Ozawa, Yusuke; Watanabe, Kenji; Izuo, Naotaka; Toda, Toshihiko; Yokote, Koutaro; Shimizu, Takahiko

2014-01-01

Cu-Zn superoxide dismutase (Sod1) loss causes a redox imbalance as it leads to excess superoxide generation, which results in the appearance of various aging-related phenotypes, including skin atrophy. Noble metal nanoparticles, such as palladium (Pd) and platinum (Pt) nanoparticles, are considered to function as antioxidants due to their strong catalytic activity. In Japan, a mixture of Pd and Pt nanoparticles called PAPLAL has been used to treat chronic diseases over the past 60 years. In the present study, we investigated the protective effects of PAPLAL against aging-related skin pathologies in mice. Transdermal PAPLAL treatment reversed skin thinning associated with increased lipid peroxidation in Sod1-/- mice. Furthermore, PAPLAL normalized the gene expression levels of Col1a1, Mmp2, Has2, Tnf-α, Il-6, and p53 in the skin of the Sod1-/- mice. Pt nanoparticles exhibited marked SOD and catalase activity, while Pd nanoparticles only displayed weak SOD and catalase activity in vitro. Although the SOD and catalase activity of the Pt nanoparticles significantly declined after they had been oxidized in air, a mixture of Pd and Pt nanoparticles continued to exhibit SOD and catalase activity after oxidation. Importantly, a mixture of Pd and Pt nanoparticles with a molar ratio of 3 or 4 to 1 continued to exhibit SOD and catalase activity after oxidation, indicating that Pd nanoparticles prevent the oxidative deterioration of Pt nanoparticles. These findings indicate that PAPLAL stably suppresses intrinsic superoxide generation both in vivo and in vitro via SOD and catalase activity. PAPLAL is a potentially powerful tool for the treatment of aging-related skin diseases caused by oxidative damage.

Bee venom effects on ubiquitin proteasome system in hSOD1(G85R)-expressing NSC34 motor neuron cells.

PubMed

Kim, Seon Hwy; Jung, So Young; Lee, Kang-Woo; Lee, Sun Hwa; Cai, MuDan; Choi, Sun-Mi; Yang, Eun Jin

2013-07-18

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from a progressive loss of motor neurons. Familial ALS (fALS) is caused by missense mutations in Cu, Zn-superoxide dismutase 1 (SOD1) that frequently result in the accumulation of mutant protein aggregates that are associated with impairments in the ubiquitin-proteasome system (UPS). UPS impairment has been implicated in many neurological disorders. Bee venom (BV) extracted from honey bees has been used as a traditional medicine for treating inflammatory diseases and has been shown to attenuate the neuroinflammatory events that occur in a symptomatic ALS animal model. NSC34 cells were transiently transfected with a WT or G85R hSOD1-GFP construct for 24 hrs and then stimulated with 2.5 μg/ml BV for 24 hrs. To determine whether a SOD1 mutation affects UPS function in NSC34 cells, we examined proteasome activity and performed western blotting and immunofluorescence using specific antibodies, such as anti-misfolded SOD1, anti-ubiquitin, anti-GRP78, anti-LC3, and anti-ISG15 antibodies. We found that GFP-hSOD1G85R overexpression induced SOD1 inclusions and reduced proteasome activity compared with the overexpression of GFP alone in NSC34 motor neuronal cells. In addition, we also observed that BV treatment restored proteasome activity and reduced the accumulation of ubiquitinated and misfolded SOD1 in GFP-hSOD1G85R-overexpressing NSC34 motor neuronal cells. However, BV treatment did not activate the autophagic pathway in these cells. Our findings suggest that BV may rescue the impairment of the UPS in ALS models.

Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain.

PubMed

Shrivastava, Rupal; Raza, Saimah; Yadav, Abhishek; Kushwaha, Pramod; Flora, Swaran J S

2014-07-01

Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.

17β-Estradiol Alters Oxidative Stress Response Protein Expression and Oxidative Damage in the Uterus

PubMed Central

Yuan, Lisi; Dietrich, Alicia K.; Nardulli, Ann M.

2014-01-01

The steroid hormone 17β-estradiol (E2) has profound effects on the uterus. However, with the E2-induced increase in uterine cell proliferation and metabolism comes increased production of reactive oxygen species (ROS). We examined the expression of an interactive network of oxidative stress response proteins including thioredoxin (Trx), Cu/Zn superoxide dismutase (SOD1), apurinic endonuclease (Ape1), and protein disulfide isomerase (PDI). We demonstrated that treatment of ovariectomized C57BL/6J female mice with E2 increased the mRNA and protein levels of Trx, but decreased SOD1 and Ape1 mRNA and protein expression. In contrast, E2 treatment increased PDI protein levels but had no effect on PDI transcript levels.Interestingly, E2 treatment also increased two markers of cellular damage, lipid peroxidation and protein carbonylation. Our studies suggest that the decreased expression of SOD1 and Ape1 caused by E2 treatment may in the long term result in disruption of ROS regulation and play a role in endometrial carcinogenesis. PMID:24103313

Low-frequency magnetic fields do not aggravate disease in mouse models of Alzheimer's disease and amyotrophic lateral sclerosis

PubMed Central

Liebl, Martina P.; Windschmitt, Johannes; Besemer, Anna S.; Schäfer, Anne-Kathrin; Reber, Helmut; Behl, Christian; Clement, Albrecht M.

2015-01-01

Low-frequency magnetic fields (LF-MF) generated by power lines represent a potential environmental health risk and are classified as possibly carcinogenic by the World Health Organization. Epidemiological studies indicate that LF-MF might propagate neurodegenerative diseases like Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS). We conducted a comprehensive analysis to determine whether long-term exposure to LF-MF (50 Hz, 1 mT) interferes with disease development in established mouse models for AD and ALS, namely APP23 mice and mice expressing mutant Cu/Zn-superoxide dismutase (SOD1), respectively. Exposure for 16 months did not aggravate learning deficit of APP23 mice. Likewise, disease onset and survival of SOD1G85R or SOD1G93A mice were not altered upon LF-MF exposure for ten or eight months, respectively. These results and an extended biochemical analysis of protein aggregation, glial activation and levels of toxic protein species suggests that LF-MF do not affect cellular processes involved in the pathogenesis of AD or ALS. PMID:25717019

ALS-linked mutant SOD1 proteins promote Aβ aggregates in ALS through direct interaction with Aβ.

PubMed

Jang, Ja-Young; Cho, Hyungmin; Park, Hye-Yoon; Rhim, Hyangshuk; Kang, Seongman

2017-11-04

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motor neurons. Aggregation of ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) is a hallmark of a subset of familial ALS (fALS). Recently, intracellular amyloid-β (Aβ) is detected in motor neurons of both sporadic and familial ALS. We have previously shown that intracellular Aβ specifically interacts with G93A, an ALS-linked SOD1 mutant. However, little is known about the pathological and biological effect of this interaction in neurons. In this study, we have demonstrated that the Aβ-binding region is exposed on the SOD1 surface through the conformational changes due to misfolding of SOD1. Interestingly, we found that the intracellular aggregation of Aβ is enhanced through the direct interaction of Aβ with the Aβ-binding region exposed to misfolded SOD1. Ultimately, increased Aβ aggregation by this interaction promotes neuronal cell death. Consistent with this result, Aβ aggregates was three-fold higher in the brains of G93A transgenic mice than those of non Tg. Our study provides the first direct evidence that Aβ, an AD-linked factor, is associated to the pathogenesis of ALS and provides molecular clues to understand common aggregation mechanisms in the pathogenesis of neurodegenerative diseases. Furthermore, it will provide new insights into the development of therapeutic approaches for ALS. Copyright © 2017 Elsevier Inc. All rights reserved.

Advanced age-related denervation and fiber-type grouping in skeletal muscle of SOD1 knockout mice.

PubMed

Kostrominova, Tatiana Y

2010-11-30

In this study skeletal muscles from 1.5- and 10-month-old Cu/Zn superoxide dismutase (SOD1) homozygous knockout (JLSod1(-/-)) mice obtained from The Jackson Laboratory (C57Bl6/129SvEv background) were compared with muscles from age- and sex-matched heterozygous (JLSod1(+/-)) littermates. The results of this study were compared with previously published data on two different strains of Sod1(-/-) mice: one from Dr. Epstein's laboratory (ELSod1(-/-); C57Bl6 background) and the other from Cephalon, Inc. (CSod1(-/-); 129/CD-1 background). Grouping of succinate dehydrogenase-positive fibers characterized muscles of Sod1(-/-) mice from all three strains. The 10-month-old Sod1(-/-)C and JL mice displayed pronounced denervation of the gastrocnemius muscle, whereas the ELSod1(-/-) mice displayed a small degree of denervation at this age, but developed accelerated age-related denervation later on. Denervation markers were up-regulated in skeletal muscle of 10-month-old JLSod1(-/-) mice. This study is the first to show that metallothionein mRNA and protein expression was up-regulated in the skeletal muscle of 10-month-old JLSod1(-/-) mice and was mostly localized to the small atrophic muscle fibers. In conclusion, all three strains of Sod1(-/-) mice develop accelerated age-related muscle denervation, but the genetic background has significant influence on the progress of denervation. Copyright © 2010 Elsevier Inc. All rights reserved.

TBBPA induces developmental toxicity, oxidative stress, and apoptosis in embryos and zebrafish larvae (Danio rerio).

PubMed

Wu, Shengmin; Ji, Guixiang; Liu, Jining; Zhang, Shenghu; Gong, Yang; Shi, Lili

2016-10-01

Tetrabromobisphenol A (TBBPA) is currently one of the most frequently used brominated flame retardants and can be considered as a high production volume chemical. In this study, zebrafish embryos and larvae served as a biological model to evaluate TBBPA-induced developmental toxicity, oxidative stress, oxidant-associated gene expression, and cell apoptosis. Abnormalities, including hyperemia and pericardial edema, were induced in zebrafish larvae. The results showed that toxicity endpoints such as hatching rate, survival rate, malformation rate, and growth rate had a significant dose-response relationship with TBBPA. Further studies revealed that TBBPA did not alter the enzyme activities of Copper/Zinc Superoxide dismutase (Cu/Zn-SOD), catalase (CAT), and glutathioneperoxidase (GPx) at 0.10 mg/L, but decreased activities following exposure to 0.40, 0.70, and 1.00 mg/L. Despite the significantly decreased gene expression of Cu/Zn-SOD, CAT, and GPx1a in the 1.00 mg/L treatment group, other treatments (0.10, 0.40, 0.70 mg/L) did not alter gene expression. Moreover, Acridine orange staining results showed that apoptotic cells mainly accumulated in the brain, heart, and tail, indicating possible TBBPA-induced brain, cardiac, and blood circulation system impairment in zebrafish embryos and larvae. Histological analysis also showed evidence of obvious heart impairment in TBBPA-treated groups. This study provides new evidence on the developmental toxicity, oxidative stress, and apoptosis of embryos and zebrafish larvae, which is important for the evaluation of environmental toxicity and chemical risk. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1241-1249, 2016. © 2015 Wiley Periodicals, Inc.

Different effects of blue and red light-emitting diodes on antioxidant responses in the liver and ovary of zebrafish Danio rerio.

PubMed

Yuan, Shuang-Shuang; Xu, Huan-Zhi; Liu, Li-Qin; Zheng, Jia-Lang

2017-04-01

The present study assessed the effects of a white fluorescent bulb (the control) and two different light-emitting diodes (blue LEDs, LDB; red, LDR) on growth, morphology, and oxidative stress in the liver and ovary of zebrafish for 5 weeks. Growth maintained relatively constant under LDB condition, but was reduced under LDR condition. In the liver, hepatosomatic index (HSI) and protein carbonylation (PC) increased under LDR condition, whereas lipid peroxidation (LPO) declined and HSI remained unchanged under LDB condition. The decrease in oxidative damage by LDB could be attributed to the up-regulated levels of mRNA, protein, and activity of Cu/Zn-SOD and CAT. A failure to activate the activity of both enzymes may result in the enhanced PC levels under LDR condition, though both genes were up-regulated at transcriptional and translational levels. In the ovary, although gonadosomatic index sharply increased under LDR condition, LPO and PC dramatically accumulated. The increase in oxidative damage by LDR might result from the down-regulated levels of protein and activity of Cu/Zn-SOD and CAT, though both genes were up-regulated at a transcriptional level. Furthermore, a sharp increase in expression of transcription factor Nrf2 that targets antioxidant genes was observed in the liver but not in the ovary under LDB and LDR conditions. In conclusion, our data demonstrated a positive effect of LDB and negative effect of LDR on fish antioxidant defenses, emphasizing the potentials of LDB as an effective light source in fish farming.

Absence of Nrf2 or Its Selective Overexpression in Neurons and Muscle Does Not Affect Survival in ALS-Linked Mutant hSOD1 Mouse Models

PubMed Central

Vargas, Marcelo R.; Burton, Neal C.; Gan, Li; Johnson, Delinda A.; Schäfer, Matthias; Werner, Sabine; Johnson, Jeffrey A.

2013-01-01

The nuclear factor erythroid 2-related factor 2 (Nrf2) governs the expression of antioxidant and phase II detoxifying enzymes. Nrf2 activation can prevent or reduce cellular damage associated with several types of injury in many different tissues and organs. Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons and subsequent muscular atrophy. We have previously shown that Nrf2 activation in astrocytes delays neurodegeneration in ALS mouse models. To further investigate the role of Nrf2 in ALS we determined the effect of absence of Nrf2 or its restricted overexpression in neurons or type II skeletal muscle fibers on symptoms onset and survival in mutant hSOD1 expressing mice. We did not observe any detrimental effect associated with the lack of Nrf2 in two different mutant hSOD1 animal models of ALS. However, restricted Nrf2 overexpression in neurons or type II skeletal muscle fibers delayed disease onset but failed to extend survival in hSOD1G93A mice. These results highlight the concept that not only the pharmacological target but also the cell type targeted may be relevant when considering a Nrf2-mediated therapeutic approach for ALS. PMID:23418589

Absence of Nrf2 or its selective overexpression in neurons and muscle does not affect survival in ALS-linked mutant hSOD1 mouse models.

PubMed

Vargas, Marcelo R; Burton, Neal C; Kutzke, Jennifer; Gan, Li; Johnson, Delinda A; Schäfer, Matthias; Werner, Sabine; Johnson, Jeffrey A

2013-01-01

The nuclear factor erythroid 2-related factor 2 (Nrf2) governs the expression of antioxidant and phase II detoxifying enzymes. Nrf2 activation can prevent or reduce cellular damage associated with several types of injury in many different tissues and organs. Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons and subsequent muscular atrophy. We have previously shown that Nrf2 activation in astrocytes delays neurodegeneration in ALS mouse models. To further investigate the role of Nrf2 in ALS we determined the effect of absence of Nrf2 or its restricted overexpression in neurons or type II skeletal muscle fibers on symptoms onset and survival in mutant hSOD1 expressing mice. We did not observe any detrimental effect associated with the lack of Nrf2 in two different mutant hSOD1 animal models of ALS. However, restricted Nrf2 overexpression in neurons or type II skeletal muscle fibers delayed disease onset but failed to extend survival in hSOD1(G93A) mice. These results highlight the concept that not only the pharmacological target but also the cell type targeted may be relevant when considering a Nrf2-mediated therapeutic approach for ALS.

Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis.

PubMed

Lamb, David J; Tickner, Michelle L; Hourani, Susanna M O; Ferns, Gordon A A

2005-08-01

The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R(2) = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R(2) = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis.

Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis

PubMed Central

Lamb, David J; Tickner, Michelle L; Hourani, Susanna M O; Ferns, Gordon A A

2005-01-01

The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R2 = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R2 = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis. PMID:16045547

Increasing dissolved-oxygen disrupts iron homeostasis in production cultures of Escherichia coli.

PubMed

Baez, Antonino; Shiloach, Joseph

2017-01-01

The damaging effect of high oxygen concentration on growth of Escherichia coli is well established. Over-oxygenation increases the intracellular concentration of reactive oxygen species (ROS), causing the destruction of the [4Fe-4S] cluster of dehydratases and limiting the biosynthesis of both branched-chain amino acids and nicotinamide adenine dinucleotide. A key enzyme that reduces the damaging effect of superoxide is superoxide dismutase (SOD). Its transcriptional regulation is controlled by global transcription regulators that respond to changes in oxygen and iron concentrations and pH. Production of biological compounds from E. coli is currently achieved using cultures grown to high cell densities which require oxygen-enriched air supply. It is, therefore, important to study the effect of over-oxygenation on E. coli metabolism and the bacterial protecting mechanism. The effect of over-oxygenation on the superoxide dismutase regulation system was evaluated in cultures grown in a bioreactor by increasing the oxygen concentration from 30 to 300 % air saturation. Following the change in the dissolved oxygen (DO), the expression of sodC, the periplasmic CuZn-containing SOD, and sodA, the cytosolic Mn-containing SOD, was higher in all the tested strains, while the expression of the sodB, the cytosolic Fe-containing SOD, was lower. The down-regulation of the sodB was found to be related to the activation of the small RNA RyhB. It was revealed that iron homeostasis, in particular ferric iron, was involved in the RyhB activation and in sodB regulation but not in sodA. Supplementation of amino acids to the culture medium reduced the intracellular ROS accumulation and reduced the activation of both SodA and SodC following the increase in the oxygen concentration. The study provides evidence that at conditions of over-oxygenation, sodA and sodC are strongly regulated by the amount of ROS, in particular superoxide; and sodB is regulated by iron availability through the small RNA RyhB. In addition, information on the impact of NADH, presence of amino acids and type of iron on SOD regulation, and consequently, on the ROS concentration is provided.

Oxidative stress markers in the blood of persons with different stages of obstructive sleep apnea syndrome.

PubMed

Cofta, S; Wysocka, E; Piorunek, T; Rzymkowska, M; Batura-Gabryel, H; Torlinski, L

2008-12-01

The aim of the study was to determine some biochemical factors reflecting oxidant-antioxidant balance in the blood of patients being in different stages of the obstructive sleep apnea syndrome (OSAS). The patients, suspected of OSAS, were submitted to biochemical and somnographic examinations. APolyMesam device was used to establish the severity of apnea episodes. The control group was composed of subjects without OSAS. The following parameters were determined: concentration of plasma total antioxidant status, TAS; activity of erythrocyte Cu, Zn-superoxide dysmutase, SOD; plasma lipid peroxidation products, TBARS. The OSAS patients had lower levels of SOD and TAS, and increased level of TBARS. We conclude that oxidative stress markers increase in the blood of OSAS patients to a variable degree, depending on the severity of the syndrome and, therefore, may be suitable for a clinical follow-up of such patients.

Decreased stability and increased formation of soluble aggregates by immature superoxide dismutase do not account for disease severity in ALS

PubMed Central

Vassall, Kenrick A.; Stubbs, Helen R.; Primmer, Heather A.; Tong, Ming Sze; Sullivan, Sarah M.; Sobering, Ryan; Srinivasan, Saipraveen; Briere, Lee-Ann K.; Dunn, Stanley D.; Colón, Wilfredo; Meiering, Elizabeth M.

2011-01-01

Protein aggregation is a hallmark of many diseases, including amyotrophic lateral sclerosis (ALS), where aggregation of Cu/Zn superoxide dismutase (SOD1) is implicated in causing neurodegeneration. Recent studies have suggested that destabilization and aggregation of the most immature form of SOD1, the disulfide-reduced, unmetallated (apo) protein is particularly important in causing ALS. We report herein in depth analyses of the effects of chemically and structurally diverse ALS-associated mutations on the stability and aggregation of reduced apo SOD1. In contrast with previous studies, we find that various reduced apo SOD1 mutants undergo highly reversible thermal denaturation with little aggregation, enabling quantitative thermodynamic stability analyses. In the absence of ALS-associated mutations, reduced apo SOD1 is marginally stable but predominantly folded. Mutations generally result in slight decreases to substantial increases in the fraction of unfolded protein. Calorimetry, ultracentrifugation, and light scattering show that all mutations enhance aggregation propensity, with the effects varying widely, from subtle increases in most cases, to pronounced formation of 40–100 nm soluble aggregates by A4V, a mutation that is associated with particularly short disease duration. Interestingly, although there is a correlation between observed aggregation and stability, there is minimal to no correlation between observed aggregation, predicted aggregation propensity, and disease characteristics. These findings suggest that reduced apo SOD1 does not play a dominant role in modulating disease. Rather, additional and/or multiple forms of SOD1 and additional biophysical and biological factors are needed to account for the toxicity of mutant SOD1 in ALS. PMID:21257910

Modulation of innate immunity and gene expressions in white shrimp Litopenaeus vannamei following long-term starvation and re-feeding

PubMed Central

Lin, Yong-Chin; Chen, Jiann-Chu; C. Man, Siti Nursafura; W. Morni, Wan Zabidii; N.A. Suhaili, Awangku Shahrir; Cheng, Sha-Yen; Hsu, Chih-Hung

2012-01-01

The survival rate, weight loss, immune parameters, resistance against Vibrio alginolyticus and white-spot syndrome virus (WSSV), and expressions of lipopolysaccharide- and ß-glucan-binding protein (LGBP), peroxinectin (PX), prophenoloxidase-activating enzyme (ppA), prophenoloxidase (proPO) I, proPO II, α2-macroglobulin (α2-M), integrin ß, heat shock protein 70 (HSP70), cytosolic manganese superoxide dismutase (cytMnSOD), mitochondrial manganese superoxide dismutase (mtMnSOD), and extracellular copper and zinc superoxide dismutase (ecCuZnSOD) were examined in the white shrimp Litopenaeus vannamei (8.18 ± 0.86 g body weight) which had been denied food (starved) for up to 14–28 days. Among shrimp which had been starved for 7, 14, 21, and 28 days, 100%, 90%, 71%, and 59% survived, and they lost 3.2%, 7.3%, 9.2%, and 10.4% of their body weight, respectively. Hyaline cells (HCs), granular cells (GCs, including semi-granular cells), the total haemocyte count (THC), phenoloxidase (PO) activity, respiratory bursts (RBs), and SOD activity significantly decreased in shrimp which had been starved for 1, 1, 1, 5, 14, and 3 days, respectively. The expression of integrin ß significantly decreased after 0.5–5 days of starvation, whereas the expressions of LGBP, PX, proPO I, proPO II, ppA, and α2-M increased after 0.5–1 days. Transcripts of all genes except ecCuZnSOD decreased to the lowest level after 5 days, and tended to background values after 7 and 14 days. Cumulative mortality rates of 7-day-starved shrimp challenged with V. alginolyticus and WSSV were significantly higher than those of challenged control-shrimp for 1–7 and 1–4 days, respectively. In another experiment, immune parameters of shrimp which had been starved for 7 and 14 days and then received normal feeding (at 5% of their body weight daily) were examined after 3, 6, and 12 h, and 1, 3, and 5 days. All immune parameters of 7-day-starved shrimp were able to return to their baseline values after 5 days of re-feeding except for GCs, whereas all parameters of 14-day-starved shrimp failed to return to the baseline values even with 5 days of re-feeding. It was concluded that shrimp starved for 14 days exhibited three stages of modulation of gene expression, together with reductions in immune parameters, and decreased resistance against pathogens. PMID:24371579

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

PubMed Central

Doñate, F; Juarez, J C; Burnett, M E; Manuia, M M; Guan, X; Shaw, D E; Smith, E L P; Timucin, C; Braunstein, M J; Batuman, O A; Mazar, A P

2008-01-01

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development. PMID:18253124

Superoxide and Peroxynitrite in Atherosclerosis

NASA Astrophysics Data System (ADS)

White, C. Roger; Brock, Tommy A.; Chang, Ling-Yi; Crapo, James; Briscoe, Page; Ku, David; Bradley, William A.; Gianturco, Sandra H.; Gore, Jeri; Freeman, Bruce A.; Tarpey, Margaret M.

1994-02-01

The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (^.NO) with superoxide (O^-_2), yielding the oxidant peroxynitrite (ONOO^-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of ^.NO reaction with O^-_2. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of β very low density lipoprotein with ONOO^- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O^-_2 with ^.NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting ^.NO stimulation of vascular smooth muscle guanylate cyclase activity.

Usefulness of oxidative stress biomarkers evaluated in the snout scraping, serum and Peripheral Blood Cells of Crocodylus moreletii from Southeast Campeche for assessment of the toxic impact of PAHs, metals and total phenols.

PubMed

Dzul-Caamal, Ricardo; Hernández-López, Abigail; Gonzalez-Jáuregui, Mauricio; Padilla, Sergio E; Girón-Pérez, Manuel Ivan; Vega-López, Armando

2016-10-01

In this study, we assessed the effects of inorganic and organic pollutants [As, Cu, Fe, Mn, Pb, Zn, PAHs (11 compounds) and total phenols] from a panel of biomarkers [O2, H2O2, thiobarbituric acid reactive substances (TBARS), carbonyl proteins (RCO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total cytochrome P450 activities] evaluated in the Snout Scraping (SS), Serum (S) and Peripheral Blood Cells (PBC) of the Morelet's crocodile (Crocodylus moreletii) inhabiting the reference locality (Lake Mocu) and polluted locality (Champoton River) using Principal Component Analysis (PCA). In male crocodiles from the reference site, only H2O2 in PBC was related to levels of fluoranthene on the Keel of Caudal Scales (KCS), but, in females, no association was detected. In contrast, a sex-linked response was detected in specimens from the polluted locality. Levels of benzo[a]pyrene, benzo[a]anthracene, chrysene, pyrene, phenanthrene, acenaphthene, Zn, Cu, and Pb in KCS of the female crocodil were related to the oxidative stress biomarkers on PBC, incluing the total CYP450 activity and levels of O2, H2O2 in serum. However, in male crocodiles, the oxidative stress in SS and in the serum (TBARS, RCO, CAT, GPx), and SOD in PBC was related to As, Pb, Cu, Fe, and benzo[a]pyrene water concentrations and to the burdens of As, Fe, Mn, indeno[1,2,3cd]pyrene in KCS. These results confirm the usefulness of minimal or non-invasive methods of evaluating the oxidative stress response for the environmental monitoring program on the wild Morelet's crocodile that is subject to special protection in Mexican guidelines. Copyright © 2016 Elsevier Inc. All rights reserved.

Ecosystems supporting clusters of sporadic TSEs demonstrate excesses of the radical-generating divalent cation manganese and deficiencies of antioxidant co factors Cu, Se, Fe, Zn. Does a foreign cation substitution at prion protein's Cu domain initiate TSE?

PubMed

Purdey, M

2000-02-01

Analyses of food chains supporting isolated clusters of sporadic TSEs (CWD in N Colorado, scrapie in Iceland, CJD in Slovakia) demonstrate a consistent 2 1/2+ fold greater concentration of the pro-oxidant divalent cation, manganese (Mn), in relation to normal levels recorded in adjoining TSE-free localities. Deficiencies of the antioxidant co factors Cu/Se/Zn/Fe and Mg, P and Na were also consistently recorded in TSE foodchains. Similarities between the clinical/pathological profile of TSEs and Mn delayed psycho-neurotoxicity in miners are cited, and a novel theory generated which suggests that sporadic TSE results from early life dependence of TSE susceptible genotypes on ecosystems characterised by this specific pattern of mineral imbalance. Low Cu/Fe induces an excessive absorption of Mn in ruminants and an increased oxidation of Mn2+ into its pro oxidant species, Mn3+, which accumulates in mitochondria of CNS astrocytes in Mn SOD deficient genotypes. Deficiencies of scavenger co factors Cu/Zn/Se/Fe in the CNS permits Mn3+ initiated chain reactions of auto-oxidant mediated neuronal degeneration to proliferate, which, in turn, up-regulates the expression of the Cu-metalloprotein, prion protein (PrP). Once the rate of PrP turnover and its demand for Cu exceeds the already depleted supply of Cu within the CNS, PrP can no longer bind sufficient Cu to maintain its conformation. Mn3+ substitutes at the vacated Cu domain on PrP, thus priming up a latent capacity for lethal auto-oxidative activity to be carried along with PrP like a 'trojan horse'; where Mn 3+ serves as the integral 'infectious' transmissible component of the misfolded PrP-cation complex. The Mn overactivation of concanavalin A binding to glycoprotein and Mn-initiated autoxidation results in a diverse pathological profile involving receptor capping, aggregation/modification of CNS membrane/cytoskeletal proteins. TSE ensues. The BSE/nv CJD strain entails a 'synthetic' induction of the same CNS mineral disturbance, where 'in utero' exposure to Cu-chelating insecticides/Mn supplements accelerates the onset of a more virulent 'strain' of adolescent TSE. Copyright 2000 Harcourt Publishers Ltd.

Interaction between dimer interface residues of native and mutated SOD1 protein: a theoretical study.

PubMed

Keerthana, S P; Kolandaivel, P

2015-04-01

Cu-Zn superoxide dismutase 1 (SOD1) is a highly conserved bimetallic protein enzyme, used for the scavenging the superoxide radicals (O2 (-)) produced due to aerobic metabolism in the mitochondrial respiratory chain. Over 100 mutations have been identified and found to be in the homodimeric structure of SOD1. The enzyme has to be maintained in its dimeric state for the structural stability and enzymatic activity. From our investigation, we found that the mutations apart from the dimer interface residues are found to affect the dimer stability of protein and hence enhancing the aggregation and misfolding tendency of mutated protein. The homodimeric state of SOD1 is found to be held together by the non-covalent interactions. The molecular dynamics simulation has been used to study the hydrogen bond interactions between the dimer interface residues of the monomers in native and mutated forms of SOD1 in apo- and holo-states. The results obtained by this analysis reveal the fact that the loss of hydrogen bond interactions between the monomers of the dimer is responsible for the reduced stability of the apo- and holo-mutant forms of SOD1. The conformers with dimer interface residues in native and mutated protein obtained by the molecular dynamics simulation is subjected to quantum mechanical study using M052X/6-31G(d) level of theory. The charge transfer between N-H···O interactions in the dimer interface residues were studied. The weak interaction between the monomers of the dimer accounts for the reduced dimerization and enhanced deformation energy in the mutated SOD1 protein.

Protective effects of melatonin against 12C6+ beam irradiation-induced oxidative stress and DNA injury in the mouse brain

NASA Astrophysics Data System (ADS)

Wu, Z. H.; Zhang, H.; Wang, X. Y.; Yang, R.; Liu, B.; Liu, Y.; Zhao, W. P.; Feng, H. Y.; Xue, L. G.; Hao, J. F.; Niu, B. T.; Wang, Z. H.

2012-01-01

The purpose of this experiment was to estimate the protective effects of melatonin against radiation-induced brain damages in mice induced by heavy ion beams. Kun-Ming mice were randomly divided into five groups: normal control group, irradiation control group, and three different doses of melatonin (5, 10, and 20 mg/kg, i.p.) treated groups. Apart from the normal control group, the other four groups were exposed to whole-body 4.0 Gy carbon ion beam irradiation (approximately 0.5 Gy/min) after i.p. administration of normal saline or melatonin 1 h before irradiation. The oxidative redox status of brain tissue was assessed by measurement of malondiadehyde (MDA) levels, total superoxide dismutase (T-SOD), cytosolic superoxide dismutase (Cu/ZnSOD, SOD1) and mitochondrial superoxide dismutase (MnSOD, SOD2) activities at 8 h after irradiation. DNA damages were determined using the Comet assay and apoptosis and cell cycle distribution were detected by flow cytometric analyses. A dramatic dose-dependent decrease in MDA levels, tail moment, rates of tailing cells, and apoptosis, and a dose-dependent increase in T-SOD and SOD2 activities, in brain tissues in the melatonin-treated groups were detected compared with the irradiation only group. Furthermore, flow cytometric analysis demonstrated that the percentage of brain cells in the G0/G1 phase decreased significantly, while those in the S and G2/M stage increased dramatically, with mice pretreated with melatonin compared to the irradiation control group. These data indicate that melatonin has protective effects against irradiation-induced brain injury, and that its underlying protective mechanisms may relate to modulation of oxidative stress induced by heavy ionirradiation.

Marked synergism between mutant SOD1 and glutamate transport inhibition in the induction of motor neuronal degeneration in spinal cord slice cultures.

PubMed

Yin, Hong Z; Weiss, John H

2012-04-11

Loss of astrocytic glutamate transport capacity in ALS spinal cord supports an excitotoxic contribution to motor neuron (MN) damage in the disease, and dominant gain of function mutations in Cu/Zn superoxide dismutase (SOD1) cause certain familial forms of ALS. We have used organotypic slice cultures from wild type and G93A SOD1 mutant rat spinal cords to examine interactions between excitotoxicity and the presence of mutant SOD1 in the induction of MN degeneration. Slice cultures were prepared from 1 week old pups, and after an additional week in vitro, some were exposed to either a low level (30 μM) of the glutamate uptake inhibitor, trans-pyrrolidine-2,4-dicarboxylic acid (PDC) for 3 weeks, or a higher level (50 μM) for 48 h, followed by histochemical labeling to assess MN injury. In wild type animals these exposures caused relatively little MN degeneration. Similarly, little MN degeneration was seen in slices from SOD1 mutant animals that were not exposed to PDC. However, addition of PDC to SOD1 mutant slices resulted in substantial MN injury, which was markedly attenuated by a Ca2+ permeable AMPA-type (Ca-AMPA) glutamate channel blocker, or by a nitric oxide synthase antagonist. These observations illustrate the utility of the organotypic culture model for the investigation of intracellular interactions underlying MN degeneration in ALS, and support the hypothesis that activation of Ca-AMPA channels on MNs provides a metabolic burden that synergizes with deleterious effects of mutant SOD1 in the induction of MN injury. Copyright © 2012 Elsevier B.V. All rights reserved.

First-principles study of defect formation in a photovoltaic semiconductor Cu2ZnGeSe4

NASA Astrophysics Data System (ADS)

Nishihara, Hironori; Maeda, Tsuyoshi; Wada, Takahiro

2018-02-01

The formation energies of neutral Cu, Zn, Ge, and Se vacancies in kesterite-type Cu2ZnGeSe4 were evaluated by first-principles pseudopotential calculations using plane-wave basis functions. The calculations were performed at typical points in Cu-(Zn1/2Ge1/2)-Se and Cu3Se2-ZnSe-GeSe2 pseudoternary phase diagrams for Cu2ZnGeSe4. The results were compared with those for Cu2ZnSnSe4, Cu2ZnGeS4, and Cu2ZnSnS4 calculated using the same version of the CASTEP program code. The results indicate that Cu vacancies are easily formed in Cu2ZnGeSe4 under the Cu-poor condition as in the above compounds and CuInSe2, suggesting that Cu2ZnGeSe4 is also a preferable p-type absorber material for thin-film solar cells. The formation energies of possible antisite defects, such as CuZn and CuGe, and of possible complex defects, such as CuZn+ZnCu, were also calculated and compared within the above materials. The antisite defect of CuZn, which has the smallest formation energy within the possible defects, is concluded to be the most hardly formed in Cu2ZnGeSe4 among the compounds.

Effects of UV-B irradiation on isoforms of antioxidant enzymes and their activities in red alga Grateloupia filicina (Rhodophyta)

NASA Astrophysics Data System (ADS)

Zhao, Jiqiang; Li, Lixia

2014-11-01

Macroalgae in a littoral zone are inevitably exposed to UV-B irradiance. We analyzed the effects of UV-B on isoenzyme patterns and activities of superoxide dismutase (SOD), peroxidase (POX), catalase (CAT), and ascorbate peroxidase (APX) of red algae Grateloupia filicina (Lamour.) C. Agardh. The activities of SOD, CAT, and APX changed in response to UV-B in a time- and dose-dependent manner. POX activity increased significantly under all three UV-B treatments. The enzymatic assay showed three distinct bands of SODI (Mn-SOD), SODII (Fe-SOD), and SODIII (CuZn-SOD) under a low (Luv) and medium (Muv) dose of UV-B irradiation, while SODI and SODIII activities decreased significantly when exposed to a high dose of UV-B irradiation (Huv). The activity of POX isoenzymes increased significantly after exposure to UV-B, which is consistent with the total activity. In addition, a clear decrease in activity of CATIV was detected in response to all the three doses of UV treatments. Some bands of APX isoenzyme were also clearly influenced by UV-B irradiation. Correspondingly, the daily growth rate declined under all the three exposure doses, and was especially significant under Muv and Huv treatments. These data suggest that, although the protection mechanisms of antioxidant defense system are partly inducible by UV-B to prevent the damage, G. filicina has incomplete tolerance to higher UV-B irradiation stress.

Differential effects of eNOS uncoupling on conduit and small arteries in GTP-cyclohydrolase I-deficient hph-1 mice.

PubMed

d'Uscio, Livius V; Smith, Leslie A; Katusic, Zvonimir S

2011-12-01

In the present study, we used the hph-1 mouse, which displays GTP-cyclohydrolase I (GTPCH I) deficiency, to test the hypothesis that loss of tetrahydrobiopterin (BH(4)) in conduit and small arteries activates compensatory mechanisms designed to protect vascular wall from oxidative stress induced by uncoupling of endothelial nitric oxide synthase (eNOS). Both GTPCH I activity and BH(4) levels were reduced in the aortas and small mesenteric arteries of hph-1 mice. However, the BH(4)-to-7,8-dihydrobiopterin ratio was significantly reduced only in hph-1 aortas. Furthermore, superoxide anion and 3-nitrotyrosine production were significantly enhanced in aortas but not in small mesenteric arteries of hph-1 mice. In contrast to the aorta, protein expression of copper- and zinc-containing superoxide dismutase (CuZnSOD) was significantly increased in small mesenteric arteries of hph-1 mice. Protein expression of catalase was increased in both aortas and small mesenteric arteries of hph-1 mice. Further analysis of endothelial nitric oxide synthase (eNOS)/cyclic guanosine monophosphate (cGMP) signaling demonstrated that protein expression of phosphorylated Ser(1177)-eNOS as well as basal cGMP levels and hydrogen peroxide was increased in hph-1 aortas. Increased production of hydrogen peroxide in hph-1 mice aortas appears to be the most likely mechanism responsible for phosphorylation of eNOS and elevation of cGMP. In contrast, upregulation of CuZnSOD and catalase in resistance arteries is sufficient to protect vascular tissue from increased production of reactive oxygen species generated by uncoupling of eNOS. The results of our study suggest that anatomical origin determines the ability of vessel wall to cope with oxidative stress induced by uncoupling of eNOS.

Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease.

PubMed

Davila, Hugo H; Magee, Thomas R; Vernet, Dolores; Rajfer, Jacob; Gonzalez-Cadavid, Nestor F

2004-11-01

The goal of the present study was to investigate the antifibrotic role of inducible nitric oxide synthase (iNOS) in Peyronie's disease (PD) by determining whether a plasmid expressing iNOS (piNOS) injected into a PD-like plaque can induce regression of the plaque. A PD-like plaque was induced with fibrin in the penile tunica albuginea of mice and then injected with a luciferase-expressing plasmid (pLuc), either alone or with piNOS, following luciferase expression in vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in the absence of fibrin. Tissue sections were stained for collagen, transforming growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido-reductase (XOR; oxidative stress) were estimated by Western blot analysis. Luciferase reporter expression was restricted to the penis, peaked at 3 days after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS expression also peaked at 3 days, but expression decreased at the end of treatment, when a considerable reduction of plaque size occurred. Protein nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The piNOS gene transfer regressed the PD plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in PD is defense mechanism by the tissue against fibrosis.

The cost of reproduction in women: Reproductive effort and oxidative stress in premenopausal and postmenopausal American women.

PubMed

Ziomkiewicz, Anna; Frumkin, Amara; Zhang, Yawei; Sancilio, Amelia; Bribiescas, Richard G

2018-01-01

Life history theory predicts a trade-off between female investment in reproduction and somatic maintenance, which can result in accelerated senescence. Oxidative stress has been shown to be a causal physiological mechanism for accelerated aging and a possible contributor to this trade-off. We aimed to test the hypothesis for the existence of significant associations between measures of reproductive effort and the level of oxidative stress biomarkers in premenopausal and postmenopausal American women. Serum samples and questionnaire data were collected from 63 premenopausal and postmenopausal women (mean age 53.4 years), controls in the Connecticut Thyroid Health Study, between May 2010 and December 2013. Samples were analyzed for levels of 8-OHdG and Cu/Zn-SOD using immunoassay method. Levels of oxidative damage (8-OHdG) but not oxidative defense (Cu/Zn-SOD) were negatively associated with parity and number of sons in premenopausal women (r = -0.52 for parity, r = -0.52 for number of sons, P < .01). Together, measures of reproductive effort, women's BMI, age, and menopausal status explained around 15% of variance in level of 8-OHdG. No association between reproductive effort characteristics and oxidative damage was found for postmenopausal women. We found no evidence of a trade-off between somatic maintenance as measured by 8-OHdG and reproductive effort in women from this American population. On the contrary, higher gravidity and parity in premenopausal women was associated with lower damage to cellular DNA caused by oxidative stress. These results highlight the importance of population variation and environmental conditions when testing the occurrence of life-history trade-offs. © 2017 Wiley Periodicals, Inc.

RNAi of selected candidate genes interrupts growth and development of Helicoverpa armigera.

PubMed

Chikate, Yojana R; Dawkar, Vishal V; Barbole, Ranjit S; Tilak, Priyadarshini V; Gupta, Vidya S; Giri, Ashok P

2016-10-01

Helicoverpa armigera is one of the major crop pests and is less amenable to current pest control approaches. RNA interference (RNAi) is emerging as a potent arsenal for the insect pest control over current methods. Here, we examined the effect on growth and development in H. armigera by targeting various enzymes/proteins such as proteases like trypsins (HaTry2, 3, 4 and 6), chymotrypsin (HaChy4) and cysteine protease like cathepsin (HaCATHL); glutathione S-transferases (HaGST1a, 6 and 8); esterases (HaAce4, HaJHE); catalase (HaCAT); super-oxide-dismutase (HaCu/ZnSOD); fatty acid binding protein (HaFabp) and chitin deacetylase (HaCda5b) through dsRNA approach. Significant downregulation of cognate mRNA expression and reduced activity of trypsin and GST-like enzyme were evident upon feeding candidate dsRNAs to the larvae. Among these, the highest mortality was observed in HaAce4 dsRNA fed larvae followed by HaJHE; HaCAT; HaCuZnSOD; HaFabp and HaTry3 whereas remaining ones showed relatively lower mortality. Furthermore, the dsRNA fed larvae showed significant reduction in the larval mass and abnormalities at the different stages of H. armigera development compared to their control diets. For example, malformed larvae, pupae and moth at a dose of 60μg/day were evident in high number of individual insects fed on dsRNA containing diets. Moreover, the growth and development of insects and moths were retarded in dsRNA fed larvae. These findings might provide potential new candidates for designing effective dsRNA as pesticide in crop protection. Copyright © 2016 Elsevier B.V. All rights reserved.

Bacopa monniera ameliorates cognitive impairment and neurodegeneration induced by intracerebroventricular-streptozotocin in rat: behavioral, biochemical, immunohistochemical and histopathological evidences.

PubMed

Khan, M Badruzzaman; Ahmad, Muzamil; Ahmad, Saif; Ishrat, Tauheed; Vaibhav, Kumar; Khuwaja, Gulrana; Islam, Fakhrul

2015-02-01

The standardized extract of Bacopa monniera (BM) is a complex mixture of ingredients with a uniquely wide spectrum of neuropharmacological influences upon the central nervous system including enhanced learning and memory with known antioxidant potential and protection of the brain from oxidative damage. The present study demonstrates the therapeutic efficacy of BM on cognitive impairment and oxidative damage, induced by intracerebroventricular injection of streptozotocin (ICV-STZ) in rat models. Male Wistar rats were pre-treated with BM at a selected dose (30 mg/Kg) given orally for 2 weeks and then were injected bilaterally with ICV-STZ (3 mg/Kg), while sham operated rats were received the same volume of vehicle. Behavioral parameters were subsequently monitored 2 weeks after the surgery using the Morris water maze (MWM) navigation task then were sacrificed for biochemical, immunohistochemical (Cu/Zn-SOD) and histopathological assays. ICV-STZ-infused rats showed significant loss in learning and memory ability, which were significantly improved by BM supplementation. A significant increase in thiobarbituric acid reactive species and a significant decrease in reduced glutathione, antioxidant enzymes in the hippocampus were observed in ICV-STZ rats. Moreover, decrease in Cu/Zn-SOD expression positive cells were observed in the hippocampus of ICV-STZ rats. BM supplementation significantly ameliorated all alterations induced by ICV-STZ in rats. The data suggest that ICV-STZ might cause its neurotoxic effects via the production of free radicals. Our study demonstrates that BM is a powerful antioxidant which prevents cognitive impairment, oxidative damage, and morphological changes in the ICV-STZ-infused rats. Thus, BM may have therapeutic value for the treatment of cognitive impairment.

Effect of graphene oxide on copper stress in Lemna minor L.: evaluating growth, biochemical responses, and nutrient uptake.

PubMed

Hu, Changwei; Liu, Lei; Li, Xiuling; Xu, Yundi; Ge, Zhigang; Zhao, Yongjun

2018-01-05

The wide application and unique properties of graphene oxide (GO) make it to interact with other pollutants and subsequently alter their behavior and toxicity. We evaluated the influences of GO at different concentrations (1 and 5mg/L) on copper (Cu) stress in duckweed (Lemna minor L.) GO below a concentration of 5mg/L showed no adverse effects on L. minor. The addition of Cu above 10μM represented a stress condition, which was evidenced by various parameters such as frond number, percent inhibition of growth rate (I r ), total chlorophyll content, dry weight, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). When L. minor was simultaneously exposed to GO and Cu, especially at a GO concentration of 5mg/L and a Cu level above 10μM, the increase of I r and decrease of chlorophyll content were inhibited, suggesting that the Cu stress was diminished in the presence of GO. The addition of Cu alone, ranging between 5 and 20μM, increased Cu, B, Mn, Fe, Co, and Zn uptake, but decreased P uptake. Our results suggest that GO can lessen Cu stress in L. minor via Cu adsorption, thereby protecting the plants from the damaging effects of high Cu concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

Overexpression of antioxidant enzymes in diaphragm muscle does not alter contraction-induced fatigue or recovery

PubMed Central

McClung, Joseph M.; DeRuisseau, Keith C.; Whidden, Melissa A.; Van Remmen, Holly; Richardson, Arlan; Song, Wook; Vrabas, Ioannis S.; Powers, Scott K.

2010-01-01

Low levels of reactive oxygen species (ROS) production are necessary to optimize muscle force production in unfatigued muscle. In contrast, sustained high levels of ROS production have been linked to impaired muscle force production and contraction-induced skeletal muscle fatigue. Using genetically engineered mice, we tested the hypothesis that the independent transgenic overexpression of catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD; SOD1) or manganese superoxide dismutase (MnSOD; SOD2) antioxidant enzymes would negatively affect force production in unfatigued diaphragm muscle but would delay the development of muscle fatigue and enhance force recovery after fatiguing contractions. Diaphragm muscle from wild-type littermates (WT) and from CAT, SOD1 and SOD2 overexpressing mice were subjected to an in vitro contractile protocol to investigate the force–frequency characteristics, the fatigue properties and the time course of recovery from fatigue. The CAT, SOD1 and SOD2 overexpressors produced less specific force (in N cm−2) at stimulation frequencies of 20–300 Hz and produced lower maximal tetanic force than WT littermates. The relative development of muscle fatigue and recovery from fatigue were not influenced by transgenic overexpression of any antioxidant enzyme. Morphologically, the mean cross-sectional area (in μm2) of diaphragm myofibres expressing myosin heavy chain type IIA was decreased in both CAT and SOD2 transgenic animals, and the percentage of non-contractile tissue increased in diaphragms from all transgenic mice. In conclusion, our results do not support the hypothesis that overexpression of independent antioxidant enzymes protects diaphragm muscle from contraction-induced fatigue or improves recovery from fatigue. Moreover, our data are consistent with the concept that a basal level of ROS is important to optimize muscle force production, since transgenic overexpression of major cellular antioxidants is associated with contractile dysfunction. Finally, the transgenic overexpression of independent endogenous antioxidants alters diaphragm skeletal muscle morphology, and these changes may also contribute to the diminished specific force production observed in these animals. PMID:19783618

The necrotroph Botrytis cinerea induces a non-host type II resistance mechanism in Pinus pinaster suspension-cultured cells.

PubMed

Azevedo, Herlânder; Lino-Neto, Teresa; Tavares, Rui Manuel

2008-03-01

Models of non-host resistance have failed to account for the pathogenicity of necrotrophic agents. During the interaction of Pinus pinaster (maritime pine) with the non-host necrotrophic pathogen Botrytis cinerea, the generation and scavenging of reactive oxygen species (ROS) and the induction of the hypersensitive response (HR) were analyzed. Elicitation of maritime pine suspended cells with B. cinerea spores resulted in the biphasic induction of ROS. The phase I oxidative burst was dependent on calcium influx, while the phase II oxidative burst also depended on NADPH oxidase, protein kinase activity, and de novo transcription and protein synthesis. A decline was observed in catalase (CAT) and superoxide dismutase (SOD) activity, together with the down-regulation of Fe-Sod1, chlCu, Zn-Sod1 and csApx1, suggesting a coordinated response towards a decrease in the ROS-scavenging capacity of maritime pine cells during challenge. Following the second oxidative burst, programmed cell death events characteristic of the HR were observed. The results suggest the ROS-mediated and cell-breach-independent activation of Type II non-host resistance during the P. pinaster-B. cinerea interaction.

TRX is up-regulated by fibroblast growth factor-2 in lung carcinoma.

PubMed

Deng, Zheng-Hao; Cao, Hui-Qiu; Hu, Yong-Bin; Wen, Ji-Fang; Zhou, Jian-Hua

2011-01-01

We have previously shown that exogenous fibroblast growth factor-2 (FGF-2) inhibits apoptosis of the small-cell lung cancer (SCLC) cell line NCI-H446, but the underlying mechanism remains unknown. In this study, the protein profiles of FGF-2-treated and untreated NCI-H446 cells were determined by 2-D gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and bioinformatics. Differential expression analysis of the protein profiles after FGF-2 treatment identified a total of 24 protein spots, of which nine were up-regulated and 15 were down-regulated. Four proteins were identified by MALDI-TOF-MS: thioredoxin (TRX), visfatin, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) and Cu/Zn superoxide dismutase (CuZn-SOD). Western blotting revealed that TRX was up-regulated in NCI-H446 and A549 cells treated with FGF-2. Furthermore, immunohistochemical staining confirmed that both FGF-2 and TRX were overexpressed in lung cancer tissues and could be correlated with both lymph node metastasis and clinical stage. These data indicate that TRX may be involved in the FGF-2 signaling pathway. © 2010 The Authors. APMIS © 2010 APMIS.

Antioxidant effects of a cinnamon extract in people with impaired fasting glucose that are overweight or obese.

PubMed

Roussel, Anne-Marie; Hininger, Isabelle; Benaraba, Rachida; Ziegenfuss, Tim N; Anderson, Richard A

2009-02-01

To determine the effects of a dried aqueous extract of cinnamon on antioxidant status of people with impaired fasting glucose that are overweight or obese. Twenty-two subjects, with impaired fasting blood glucose with BMI ranging from 25 to 45, were enrolled in a double-blind placebo-controlled trial. Subjects were given capsules containing either a placebo or 250 mg of an aqueous extract of cinnamon (Cinnulin PF) two times per day for 12 weeks. Plasma malondialdehyde (MDA) concentrations were assessed using high performance liquid chromatography and plasma antioxidant status was evaluated using ferric reducing antioxidant power (FRAP) assay. Erythrocyte Cu-Zn superoxide (Cu-Zn SOD) activity was measured after hemoglobin precipitation by monitoring the auto-oxidation of pyrogallol and erythrocyte glutathione peroxidase (GPx) activity by established methods. FRAP and plasma thiol (SH) groups increased, while plasma MDA levels decreased in subjects receiving the cinnamon extract. Effects were larger after 12 than 6 weeks. There was also a positive correlation (r = 0.74; p = 0.014) between MDA and plasma glucose. This study supports the hypothesis that the inclusion of water soluble cinnamon compounds in the diet could reduce risk factors associated with diabetes and cardiovascular disease.

Superoxide dismutase 1 mutation in a cellular model of amyotrophic lateral sclerosis shifts energy generation from oxidative phosphorylation to glycolysis.

PubMed

Allen, Scott P; Rajan, Sandeep; Duffy, Lynn; Mortiboys, Heather; Higginbottom, Adrian; Grierson, Andrew J; Shaw, Pamela J

2014-06-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder involving the progressive degeneration of motor neurons in the brain and spinal cord. Mitochondrial dysfunction plays a key role in ALS disease progression and has been observed in several ALS cellular and animal models. Here, we show that fibroblasts isolated from ALS cases with a Cu/Zn superoxide dismutase (SOD1) I113T mutation recapitulate these mitochondrial defects. Using a novel technique, which measures mitochondrial respiration and glycolytic flux simultaneously in living cells, we have shown that SOD1 mutation causes a reduction in mitochondrial respiration and an increase in glycolytic flux. This causes a reduction in adenosine triphosphate produced by oxidative phosphorylation and an increase in adenosine triphosphate produced by glycolysis. Switching the energy source from glucose to galactose caused uncoupling of mitochondria with increased proton leak in SOD1(I113T) fibroblasts. Assessment of the contribution of fatty acid oxidation to total respiration, suggested that fatty acid oxidation is reduced in SOD1 ALS fibroblasts, an effect which can be mimicked by starving the control cells of glucose. These results highlight the importance of understanding the interplay between the major metabolic pathways, which has the potential to lead to strategies to correct the metabolic dysregulation observed in ALS cases. Copyright © 2014 Elsevier Inc. All rights reserved.

Overproduction of superoxide dismutase and catalase confers cassava resistance to Tetranychus cinnabarinus

PubMed Central

Lu, Fuping; Liang, Xiao; Lu, Hui; Li, Qian; Chen, Qing; Zhang, Peng; Li, kaimian; Liu, Guanghua; Yan, Wei; Song, Jiming; Duan, Chunfang; Zhang, Linhui

2017-01-01

To explore the role of protective enzymes in cassava (Manihot esculenta Crantz) resistance to mites, transgenic cassava lines overproducing copper/zinc superoxide dismutase (MeCu/ZnSOD) and catalase (MeCAT1) were used to evaluate and molecularly confirm cassava resistance to Tetranychus cinnabarinus. Laboratory evaluation demonstrated that, compared with the control cultivar TMS60444 (wild type, WT), the survival, reproduction, development and activities of SOD and CAT in T. cinnabarinus feeding on transgenic cassava lines SC2, SC4, and SC11 significantly inhibited. Furthermore, the activities of SOD and CAT in transgenic cassava lines SC2, SC4, and SC11 damaged by T. cinnabarinus significantly increased. These findings were similar to the results in the mite-resistant cassava cultivars. Besides, field evaluation indicated that the transgenic cassava lines SC2, SC4, and SC11 were slightly damaged as the highly mite-resistant control C1115, while the highly mite-susceptible WT was severely damaged by T. cinnabarinus. Laboratory and field evaluation demonstrated that transgenic cassava lines were resistant to T. cinnabarinus, which directly confirmed that the increase in SOD and CAT activities was positively related to cassava resistance to T. cinnabarinus. These results will help in understanding the antioxidant defense responses in the cassava–mite interaction and molecular breeding of mite-resistant cassava for effective pest control. PMID:28054665

Superoxide dismutase activity of Cu-bound prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Lu, Wenchang; Bernholc, Jerry

2009-03-01

Misfolding of the prion protein, PrP, has been linked to a group of neurodegenerative diseases, including the mad cow disease in cattle and the Creutzfeldt-Jakob disease in humans. The normal function of PrP is still unknown, but it was found that the PrP can efficiently bind Cu(II) ions. Early experiments suggested that Cu-PrP complex possesses significant superoxide dismutase (SOD) activity, but later experiments failed to confirm it and at present this issue remains unresolved. Using a recently developed hybrid DFT/DFT method, which combines Kohn-Sham DFT for the solute and its first solvation shells with orbital-free DFT for the remainder of the solvent, we have investigated SOD activity of PrP. The PrP is capable of incorporating Cu(II) ions in several binding modes and our calculations find that each mode has a different SOD activity. The highest activity found is comparable to those of well-known SOD proteins, suggesting that the conflicting experimental results may be due to different bindings of Cu(II) in those experiments.

Structural, chemical and optical evaluation of Cu-doped ZnO nanoparticles synthesized by an aqueous solution method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iribarren, A., E-mail: augusto@imre.oc.uh.cu; Hernández-Rodríguez, E.; Maqueira, L.

Highlights: • Cu-doped ZnO nanoparticles obtained by chemical synthesis. • Substitutional or interstitial Cu into ZnO lead specific structural, chemical, and optical changes. • Incorporation efficiency of Cu atoms in ZnO as a function of the Cu concentration in the precursor dissolution. - Abstract: In this work a study of ZnO and Cu-doped ZnO nanoparticles obtained by chemical synthesis in aqueous media was carried out. Structural analysis gave the dominant presence of wurtzite ZnO phase forming a solid solution Zn{sub 1−x}Cu{sub x}O. For high Cu doping CuO phase is also present. For low Cu concentration the lattice shrinks due tomore » Cu atoms substitute Zn atoms. For high Cu concentration the lattice enlarges due to predominance of interstitial Cu. From elemental analysis we determined and analyzed the incorporation efficiency of Cu atoms in Zn{sub 1−x}Cu{sub x}O as a function of the Cu concentration in the precursor dissolution. Combining structural and chemical results we described the Cu/Zn precursor concentrations r{sub w} in which the solid solution of Cu in ZnO is predominant. In the region located at r{sub w} ≈ 0.2–0.3 it is no longer valid. For Cu/Zn precursor concentration r{sub w} > 0.3 interstitial Cu dominates, and some amount of copper oxide appears. As the Cu concentration increases, the effective size of nanoparticles decreases. Photoluminescence (PL) measurements of the Cu-doped ZnO nanoparticles were carried out and analyzed.« less

A Novel Locus for Familial Amyotrophic Lateral Sclerosis, on Chromosome 18q

PubMed Central

Hand, Collette K.; Khoris, Jawad; Salachas, François; Gros-Louis, François; Lopes, Ana Amélia Simões; Mayeux-Portas, Veronique; Brown, Jr., Robert H.; Meininger, Vincent; Camu, William; Rouleau, Guy A.

2002-01-01

Amyotrophic lateral sclerosis (ALS) is an adult-onset degenerative disorder characterized by the death of motor neurons in the cortex, brain stem, and spinal cord. Despite intensive research the basic pathophysiology of ALS remains unclear. Although most cases are sporadic, ∼10% of ALS cases are familial (FALS). Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause ∼20% of FALS. The gene(s) responsible for the remaining 80% of FALS remain to be found. Using a large European kindred without SOD1 mutation and with classic autosomal dominant adult-onset ALS, we have identified a novel locus by performing a genome scan and linkage analysis. The maximum LOD score is 4.5 at recombination fraction 0.0, for polymorphism D18S39. Haplotype analysis has identified a 7.5-cM, 8-Mb region of chromosome 18q21, flanked by markers D18S846 and D18S1109, as a novel FALS locus. PMID:11706389

Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis.

PubMed

Shimojo, Yosuke; Kosaka, Kunio; Noda, Yoshihiro; Shimizu, Takahiko; Shirasawa, Takuji

2010-03-01

Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease affecting motor neurons. About 2% of patients with the disease are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). The purpose of this study is to assess the effect of rosemary extract and its major constituents, rosmarinic acid (RA) and carnosic acid (CA), in human SOD1 G93A transgenic mice, which are well-established mouse models for ALS. The present study demonstrates that intraperitoneal administration of rosemary extract or RA from the presymptomatic stage significantly delayed motor dysfunction in paw grip endurance tests, attenuated the degeneration of motor neurons, and extended the life span of ALS model mice. In addition, RA administration significantly improved the clinical score and suppressed body weight loss compared with a vehicle-treated group. In conclusion, this study provides the first report that rosemary extract and, especially, RA have preventive effects in the mouse model of ALS.

Copper-zinc electrodeposition in alkaline-sorbitol medium: Electrochemical studies and structural, morphological and chemical composition characterization

NASA Astrophysics Data System (ADS)

de Almeida, M. R. H.; Barbano, E. P.; de Carvalho, M. F.; Tulio, P. C.; Carlos, I. A.

2015-04-01

The galvanostatic technique was used to analyze the electrodeposition of Cu-Zn on to AISI 1010 steel electrode from an alkaline-sorbitol bath with various proportions of the metal ions in the bath: Cu70/Zn30, Cu50/Zn50 and Cu30/Zn70. Coloration of Cu-Zn films were whitish golden, light golden, golden/gray depending on the Cu2+/Zn2+ ratios in the electrodeposition bath, deposition current density (jdep) and charge density (qdep). The highest current efficiency was ∼54.0%, at jdep -1.0 mA cm-2 and qdep 0.40 C cm-2 in the Cu70/Zn30 bath. Energy dispersive spectroscopy indicated that electrodeposits produced from the bath Cu70/Zn30 showed higher Cu content at lower jdep. Also, for same jdep the Cu content increased with qdep. Scanning electron microscopy showed that Cu-Zn electrodeposits of high quality were obtained from the Cu70/Zn30 bath, since the films were fine-grained, except the obtained at jdep -20.0 mA cm-2 and qdep 10.0 C cm-2. Also, these electrodeposits did not present cracks. X-ray analysis of the Cu-Zn electrodeposits obtained at jdep -8.0, -20.0 and -40.0 mA cm-2, in each case, with qdep 2.0 and 10.0 C cm-2, in the Cu70/Zn30 bath, suggested the occurrence of a mixture of the following phases, CuZn, CuZn5 and Cu5Zn8. Galvanostatic electrodeposits of Cu-Zn obtained from sorbitol-alkaline baths exhibited whitish golden color, with good prospects for industrial applications, especially for decorative purposes.

Active sites for CO 2 hydrogenation to methanol on Cu/ZnO catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kattel, Shyam; Ramírez, Pedro J.; Chen, Jingguang G.

The active sites over commercial copper/zinc oxide/aluminum oxide (Cu/ZnO/Al 2O 3) catalysts for carbon dioxide (CO 2) hydrogenation to methanol, the Zn-Cu bimetallic sites or ZnO-Cu interfacial sites, have recently been the subject of intense debate. Here, we report a direct comparison between the activity of ZnCu and ZnO/Cu model catalysts for methanol synthesis. By combining x-ray photoemission spectroscopy, density functional theory, and kinetic Monte Carlo simulations, we can identify and characterize the reactivity of each catalyst. Both experimental and theoretical results agree that ZnCu undergoes surface oxidation under the reaction conditions so that surface Zn transforms into ZnO andmore » allows ZnCu to reach the activity of ZnO/Cu with the same Zn coverage. These results highlight a synergy of Cu and ZnO at the interface that facilitates methanol synthesis via formate intermediates.« less

Active sites for CO 2 hydrogenation to methanol on Cu/ZnO catalysts

DOE PAGES

Kattel, Shyam; Ramírez, Pedro J.; Chen, Jingguang G.; ...

2017-03-23

The active sites over commercial copper/zinc oxide/aluminum oxide (Cu/ZnO/Al 2O 3) catalysts for carbon dioxide (CO 2) hydrogenation to methanol, the Zn-Cu bimetallic sites or ZnO-Cu interfacial sites, have recently been the subject of intense debate. Here, we report a direct comparison between the activity of ZnCu and ZnO/Cu model catalysts for methanol synthesis. By combining x-ray photoemission spectroscopy, density functional theory, and kinetic Monte Carlo simulations, we can identify and characterize the reactivity of each catalyst. Both experimental and theoretical results agree that ZnCu undergoes surface oxidation under the reaction conditions so that surface Zn transforms into ZnO andmore » allows ZnCu to reach the activity of ZnO/Cu with the same Zn coverage. These results highlight a synergy of Cu and ZnO at the interface that facilitates methanol synthesis via formate intermediates.« less

An Optimal Dietary Zinc Level of Brown-Egg Laying Hens Fed a Corn-Soybean Meal Diet.

PubMed

Qin, Shizhen; Lu, Lin; Zhang, Xichun; Liao, Xiudong; Zhang, Liyang; Guo, Yanli; Luo, Xugang

2017-06-01

An experiment was conducted to estimate the optimal dietary zinc (Zn) level of brown-egg laying hens fed a corn-soybean meal diet from 20 to 40 weeks of age. A total of 120 20-week-old Beijing Red commercial laying hens were randomly allotted by bodyweight to one of five treatments with six replicates of four birds each in a completely randomized design, and fed a Zn-unsupplemented corn-soybean meal basal diet containing 27.95 mg Zn/kg by analysis and the basal diets supplemented with 30, 60, 90, or 120 mg Zn/kg as Zn sulfate (reagent grade ZnSO 4 ·7H 2 O) for a duration of 20 weeks. Laying performance, egg quality, tissue Zn concentrations, and activities of serum alkaline phosphatase (AKP), and liver copper-Zn superoxide dismutase (CuZnSOD) were measured. Regression analyses were performed to estimate an optimal dietary Zn level whenever a significant quadratic response (P < 0.05) was observed. Tibia Zn concentration (P = 0.002) and serum AKP activity (P = 0.010) showed significant quadratic responses to dietary supplemental Zn levels. The estimates of dietary Zn requirements for brown-egg laying hens from 20 to 40 weeks of age were 71.95 and 64.63 mg/kg for tibia Zn concentration and serum AKP activity, respectively. The results from this study indicate that the tibia Zn might be a more suitable and reliable parameter for Zn requirement estimation, and the optimal dietary Zn level would be about 72 mg/kg for brown-egg laying hens fed a corn-soybean meal diet from 20 to 40 weeks of age.

Micronutrients and macronutrients and parameters of antioxidative ability in saliva of women: inhabitants of Krakow (Poland) in the course of uncomplicated singleton pregnancy.

PubMed

Kolarzyk, Emilia; Pietrzycka, Agata; Stepniewski, Marek; Łyszczarz, Justyna; Mendyk, Aleksander; Ostachowska-Gasior, Agnieszka

2006-01-01

There were two aims of the present study: (1) to evaluate changes of superoxide dismutase (SOD) activity and total antioxidative status measured as the ferric reducing ability of plasma (FRAP) concentration in saliva of pregnant women during the first, second, and third trimesters of singleton uncomplicated pregnancy and (2) to assess possible relations among SOD, FRAP, and intake of macronutrients and micronutrients in daily nutritional rations (DNRs) during pregnancy. Forty pregnant women aged 27.1+/-5.4 yr (examined group) and 40 healthy women (the control group) were recruited for this study. The relationship between FRAP and SOD in saliva and the intake of macronutrients (proteins, carbohydrates, total fat, saturated fatty acid, monounsaturated fatty acids, polyunsaturated fatty acids), minerals (Na, K, Ca, P, Mg, Fe, Zn, Cu, Mn), and vitamins (A, C, E, B1, B2, B6, PP) in DNR was evaluated by clustering analysis with Ward's grouping method. During pregnancy, FRAP and SOD values were lower than in the controls, but only for FRAP were the differences statistically significant (p < 0.001). For the whole pregnancy period, cluster analysis identified two major clusters for which the differentiating variables were SOD and retinoids intake, but different patterns for each trimester of pregnancy were revealed. The following were concluded: (1) FRAP values were the lowest in the second trimester. It suggests that in this trimester of uncomplicated pregnancy, women might be not fully adapted to increased demands for antioxidative mechanisms. (2) Cluster analysis showed that there were no statistical relationships between the intake of micronutrients and macronutrients in DNRs and the SOD or FRAP level in the saliva of pregnant women.

Inorganic, organic, and encapsulated minerals in vegetable meal based diets for Sparus aurata (Linnaeus, 1758)

PubMed Central

Rimoldi, Simona; Robaina, Lidia E.; Torrecillas, Silvia; Terova, Genciana; Zamorano, María J.; Karalazos, Vasileios; Hamre, Kristin; Izquierdo, Marisol

2017-01-01

Substituting fishmeal (FM) with vegetable meal (VM) can markedly affect the mineral composition of feeds, and may require additional mineral supplementation. Their bioavailability and optimal supplementation levels depend also on the form of delivery of minerals. The aim of the study was to determine the effect of different delivery forms of three major trace elements (Zn, Mn and Se) in a marine teleost. Gilthead sea bream juveniles of 22.5 g were fed a VM-based diet for 12 weeks that was either not supplemented with these minerals or supplemented with inorganic, organic, or encapsulated inorganic forms of minerals in triplicate and compared to a FM-based diet. Our results showed that mineral delivery form significantly affected the biochemical composition and morphology of posterior vertebrae. Supplementation of VM-based diets with inorganic forms of the target minerals significantly promoted growth, increased the vertebral weight and content of ash and Zn, enhanced bone mineralization and affected the vertebral shape. Conversely, encapsulation of inorganic minerals reduced fish growth and vertebral mineral content, whereas supplementation of organic minerals, enhanced bone osteogenesis by upregulating bone morphogenetic protein 2 (bmp2) gene and produced vertebrae with a larger length in relation to height. Furthermore, organic mineral forms of delivery downregulated the expression of oxidative stress related genes, such as Cu/Zn superoxide dismutase (Cu/Zn sod) and glutathione peroxidase 1 (gpx-1), suggesting thus that dietary minerals supplemented in the organic form could be reasonably considered more effective than the inorganic and encapsulated forms of supply. PMID:29093992

Molecular oxidative stress markers in olive ridley turtles (Lepidochelys olivacea) and their relation to metal concentrations in wild populations.

PubMed

Cortés-Gómez, Adriana A; Morcillo, Patricia; Guardiola, Francisco A; Espinosa, Cristobal; Esteban, María A; Cuesta, Alberto; Girondot, Marc; Romero, Diego

2018-02-01

Due to their longevity and extensive migration areas, marine turtles are able to accumulate diverse contaminants over many years and as a consequence they represent an interesting bioindicator species for marine ecosystem pollution. Metals provoke toxicological effects in many aquatic animal species, but marine turtles have been under-investigated in this area. Thus, we have determined the presence of certain inorganic elements (As, Cd, Cu, Ni, Pb, Se and Zn) in olive ridley turtles (Lepidochelys olivacea) and related them to metallothionein (MT), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) transcription and/or enzymatic activities. Gene expression of sod, cat and gr was found to be higher in blood than liver or kidney but most of the significant relationships were found in liver, not only for gene expression but also for enzyme activities. This must be related to the role the liver has as the first filter organ. Several positive relationships of sod, cat and gr gene expression in the different tissues were found in this population, as well as very high Cd concentrations. This could mean that these turtles are adapting to the metals-production of ROS and damage through a high transcription of these antioxidants. Multiple positive relationships with GR seem to be part of its compensatory effect due to the decrease of SOD production against the high and chronic exposure to certain xenobiotics. CAT, on the other hand, seems not to be used much, and glutathione detoxification of H 2 O 2 may be more important in this species. Finally, despite the very high Cd concentrations found in this population, no significant relationship was found in any tissue with metallothionein gene expression. These results, along with very high Cd concentrations and a negative relationship with Cu, lead us to consider some kind of disruption in mt gene expression in these turtles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of dietary zinc oxide nanoparticles on growth performance and antioxidative status in broilers.

PubMed

Zhao, Cui-Yan; Tan, Shu-Xian; Xiao, Xi-Yu; Qiu, Xian-Shuai; Pan, Jia-Qiang; Tang, Zhao-Xin

2014-09-01

Broilers in four groups were fed a basal diet supplemented with 60 mg/kg zinc oxide (60-ZnO; control), or 20, 60, or 100 mg/kg ZnO nanoparticles (20-, 60-, and 100-nano-ZnO, respectively). Compared with the controls, after 14 days, birds in the 20- and 60-nano-ZnO groups had significantly greater weight gains and better feed conversion ratios. However, the body weight of birds in the 100-nano-ZnO group was dramatically reduced after 28 days. Relative to the control group, the total antioxidant capability (T-AOC) in serum and liver tissue was significantly higher in the 20-nano-ZnO group at all time points and also significantly higher in the 60- and 100-nano-ZnO groups in serum on days 28 and 35 and in liver tissues on days 21 and 28. Compared with the controls, the activity of copper-zinc superoxide dismutase (Cu-Zn-SOD) was significantly greater in the 60- and 100-nano-ZnO groups in serum on days 28 and 35 and in liver tissues after 21 days. Catalase activity in serum samples was significantly higher in the 20- and 60-nano-ZnO groups relative to the control and 100-nano-ZnO birds, but catalase activity in liver tissue was not affected by different nano-ZnO levels. Malondialdehyde content in serum and liver tissues was significantly reduced in the 20-, 60-, and 100-nano-ZnO groups compared with that in the control group at all time points except day 42. Taken together, our data indicate that appropriate concentration of dietary ZnO nanoparticles improves growth performance and antioxidative capabilities in broilers, and 20 mg/kg nano-ZnO is the optimal concentration.

DNA strand breaks and TDP-43 mislocation are absent in the murine hSOD1G93A model of amyotrophic lateral sclerosis in vivo and in vitro

PubMed Central

Witte, Otto W.; Grosskreutz, Julian

2017-01-01

Mutations in the human Cu/Zn superoxide dismutase type-1 (hSOD1) gene are common in familial amyotrophic lateral sclerosis (fALS). The pathophysiology has been linked to, e.g., organelle dysfunction, RNA metabolism and oxidative DNA damage conferred by SOD1 malfunction. However, apart from metabolically evoked DNA oxidation, it is unclear whether severe genotoxicity including DNA single-strand breaks (SSBs) and double-strand breaks (DSBs), originates from loss of function of nuclear SOD1 enzyme. Factors that endogenously interfere with DNA integrity and repair complexes in hSOD1-mediated fALS remain similarly unexplored. In this regard, uncontrolled activation of transposable elements (TEs) might contribute to DNA disintegration and neurodegeneration. The aim of this study was to elucidate the role of the fALS-causing hSOD1G93A mutation in the generation of severe DNA damage beyond well-characterized DNA base oxidation. Therefore, DNA damage was assessed in spinal tissue of hSOD1G93A-overexpressing mice and in corresponding motor neuron-enriched cell cultures in vitro. Overexpression of the hSOD1G93A locus did not change the threshold for severe DNA damage per se. We found that levels of SSBs and DSBs were unaltered between hSOD1G93A and control conditions, as demonstrated in post-mitotic motor neurons and in astrocytes susceptible to replication-dependent DNA breakage. Analogously, parameters indicative of DNA damage response processes were not activated in vivo or in vitro. Evidence for a mutation-related elevation in TE activation was not detected, in accordance with the absence of TAR DNA binding protein 43 (TDP-43) proteinopathy in terms of cytoplasmic mislocation or nuclear loss, as nuclear TDP-43 is supposed to silence TEs physiologically. Conclusively, the superoxide dismutase function of SOD1 might not be required to preserve DNA integrity in motor neurons, at least when the function of TDP-43 is unaltered. Our data establish a foundation for further investigations addressing functional TDP-43 interaction with ALS-relevant genetic mutations. PMID:28832631

Soil solution dynamics of Cu and Zn in a Cu- and Zn-polluted soil as influenced by gamma-irradiation and Cu-Zn interaction.

PubMed

Luo, Y M; Yan, W D; Christie, P

2001-01-01

A pot experiment was conducted to study soil solution dynamics of Cu and Zn in a Cu/Zn-polluted soil as influenced by gamma-irradiation and Cu-Zn interaction. A slightly acid sandy loam was amended with Cu and Zn (as nitrates) either singly or in combination (100 mg Cu and 150 mg Zn kg(-1) soil) and was then gamma-irradiated (10 kGy). Unamended and unirradiated controls were included, and spring barley (Hordeum vulgare L. cv. Forrester) was grown for 50 days. Soil solution samples obtained using soil moisture samplers immediately before transplantation and every ten days thereafter were used directly for determination of Cu, Zn, pH and absorbance at 360 nm (A360). Cu and Zn concentrations in the solution of metal-polluted soil changed with time and were affected by gamma-irradiation and metal interaction. gamma-Irradiation raised soil solution Cu substantially but generally decreased soil solution Zn. These trends were consistent with increased dissolved organic matter (A360) and solution pH after gamma-irradiation. Combined addition of Cu and Zn usually gave higher soil solution concentrations of Cu or Zn compared with single addition of Cu or Zn in gamma-irradiated and non-irradiated soils, indicating an interaction between Cu and Zn. Cu would have been organically complexed and consequently maintained a relatively high concentration in the soil solution under higher pH conditions. Zn tends to occur mainly as free ion forms in the soil solution and is therefore sensitive to changes in pH. The extent to which gamma-irradiation and metal interaction affected solubility and bioavailability of Cu and Zn was a function of time during plant growth. Studies on soil solution metal dynamics provide very useful information for understanding metal mobility and bioavailability.

Corrosion and runoff rates of Cu and three Cu-alloys in marine environments with increasing chloride deposition rate.

PubMed

Odnevall Wallinder, Inger; Zhang, Xian; Goidanich, Sara; Le Bozec, Nathalie; Herting, Gunilla; Leygraf, Christofer

2014-02-15

Bare copper sheet and three commercial Cu-based alloys, Cu15Zn, Cu4Sn and Cu5Al5Zn, have been exposed to four test sites in Brest, France, with strongly varying chloride deposition rates. The corrosion rates of all four materials decrease continuously with distance from the coast, i.e. with decreasing chloride load, and in the following order: Cu4Sn>Cu sheet>Cu15Zn>Cu5Al5Zn. The patina on all materials was composed of two main layers, Cu2O as the inner layer and Cu2(OH)3Cl as the outer layer, and with a discontinuous presence of CuCl in between. Additional minor patina constituents are SnO2 (Cu4Sn), Zn5(OH)6(CO3)2 (Cu15Zn and Cu5Al5Zn) and Zn6Al2(OH)16CO3·4H2O/Zn2Al(OH)6Cl·2H2O/Zn5Cl2(OH)8·H2O and Al2O3 (Cu5Al5Zn). The observed Zn- and Zn/Al-containing corrosion products might be important factors for the lower sensitivity of Cu15Zn and Cu5Al5Zn against chloride-induced atmospheric corrosion compared with Cu sheet and Cu4Sn. Decreasing corrosion rates with exposure time were observed for all materials and chloride loads and attributed to an improved adherence with time of the outer patina to the underlying inner oxide. Flaking of the outer patina layer was mainly observed on Cu4Sn and Cu sheet and associated with the gradual transformation of CuCl to Cu2(OH)3Cl of larger volume. After three years only Cu5Al5Zn remains lustrous because of a patina compared with the other materials that appeared brownish-reddish. Significantly lower release rates of metals compared with corresponding corrosion rates were observed for all materials. Very similar release rates of copper from all four materials were observed during the fifth year of marine exposure due to an outer surface patina that with time revealed similar constituents and solubility properties. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Facile synthesis of Cu/tetrapod-like ZnO whisker compounds with enhanced photocatalytic properties

NASA Astrophysics Data System (ADS)

Liu, Hong; Liu, Huarong; Fan, Ximei

2017-09-01

Cu/tetrapod-like ZnO whisker (T-ZnOw) compounds were successfully synthesized using N2H4 \\cdot H2O as a reducing agent by a simple reduction method without any insert gas at room temperature. The crystal phase composition and morphology of the as-prepared samples were investigated by XRD, SEM and FESEM tests. The photocatalytic property of the as-prepared samples was detected by the degradation of methyl orange (MO) aqueous solution under UV irradiation. It can be found that Cu nanoparticles (CuNPs) dispersed on the surface of T-ZnOw increased with the increasing of Cu/Zn molar ratios (Cu/Zn MRs), and an octahedral structure of CuNPs was obtained when the sample was prepared with less than and equal to 7.30% Cu/Zn MR, but tended to a spherical or nanorod structure of CuNPs densely arranged on the surface of T-ZnOw, which is prepared by Cu/Zn MRs up to 22.00%. All the compounds exhibited excellent photocatalytic activity in decomposing of MO than T-ZnOw, the photocatalytic property of the samples increased with the increasing of Cu/Zn MRs up to 7.30%, while it decreases when further increasing the Cu/Zn MRs. The Schottky barrier of the Cu/T-ZnOw compound can effectively capture photoinduced electrons from the interface and enhanced the photocatalytic property of T-ZnOw.

Structure and backbone dynamics of a microcrystalline metalloprotein by solid-state NMR.

PubMed

Knight, Michael J; Pell, Andrew J; Bertini, Ivano; Felli, Isabella C; Gonnelli, Leonardo; Pierattelli, Roberta; Herrmann, Torsten; Emsley, Lyndon; Pintacuda, Guido

2012-07-10

We introduce a new approach to improve structural and dynamical determination of large metalloproteins using solid-state nuclear magnetic resonance (NMR) with (1)H detection under ultrafast magic angle spinning (MAS). The approach is based on the rapid and sensitive acquisition of an extensive set of (15)N and (13)C nuclear relaxation rates. The system on which we demonstrate these methods is the enzyme Cu, Zn superoxide dismutase (SOD), which coordinates a Cu ion available either in Cu(+) (diamagnetic) or Cu(2+) (paramagnetic) form. Paramagnetic relaxation enhancements are obtained from the difference in rates measured in the two forms and are employed as structural constraints for the determination of the protein structure. When added to (1)H-(1)H distance restraints, they are shown to yield a twofold improvement of the precision of the structure. Site-specific order parameters and timescales of motion are obtained by a gaussian axial fluctuation (GAF) analysis of the relaxation rates of the diamagnetic molecule, and interpreted in relation to backbone structure and metal binding. Timescales for motion are found to be in the range of the overall correlation time in solution, where internal motions characterized here would not be observable.

Cryoprotective role of organic Zn and Cu supplementation in goats (Capra hircus) diet.

PubMed

Arangasamy, Arunachalam; Krishnaiah, Mayasula Venkata; Manohar, Narasimhaiah; Selvaraju, Sellappan; Rani, Guvvala Pushpa; Soren, Nira Manik; Reddy, Ippala Janardhan; Ravindra, Janivara Parameshwaraiah

2018-04-01

The current study focused on cryopreservation and assessment of characters of post-thaw semen of indigenous Osmanabadi bucks maintained with standard diet, supplemented with different concentrations of organic zinc (Zn), copper (Cu) or in combination, for a period of 180 days. The different doses of organic Zn and Cu were fed per kg DM basis, Zn groups (low: Zn20, medium: Zn40 and high: Zn60), Cu groups: (low: Cu12.5, medium: Cu25 and high: Cu37.5) and combination of Zn + Cu groups (low: Zn20 + Cu12.5, medium: Zn40 + Cu25 and high: Zn60 + Cu37.5) respectively. The control group bucks were maintained mainly on the basal diet without any additional mineral supplementation. Two hundred and forty (240) semen samples were collected from 40 bucks aged 11 months, through electro ejaculator method, processed and analysed for sperm quality parameters both at pre freeze and post-thaw stage. The semen samples were diluted in Tris egg yolk extender, cooled and equilibrated for 4 h at 5 °C, cryopreserved using programmable freezer (PLANER Kryo 360-1.7) and stored at -196 °C. The organic trace minerals (Zn, Cu and Zn + Cu) protected the spermatozoa against the cryoinjury and maintained higher post-thaw semen parameters except in high Zn group. Additional feeding of organic Cu and Zn to bucks had a protective role and resulted in higher sperm liveability, plasma membrane and acrosome integrities, motility and velocity and reduced oxidative stress in supplemented goats (P < 0.05). Copyright © 2018 Elsevier Inc. All rights reserved.

An active lifestyle induces positive antioxidant enzyme modulation in peripheral blood mononuclear cells of overweight/obese postmenopausal women.

PubMed

Farinha, Juliano Boufleur; De Carvalho, Nélson Rodrigues; Steckling, Flávia Mariel; De Vargas, Liziane Da Silva; Courtes, Aline Alves; Stefanello, Sílvio Terra; Martins, Caroline Curry; Bresciani, Guilherme; Dos Santos, Daniela Lopes; Soares, Félix Alexandre Antunes

2015-01-15

The aim of this study was to investigate the effects of an active lifestyle on mitochondrial functioning, viability, bioenergetics, and redox status markers in peripheral blood mononuclear cells (PBMC) of overweight/ obese postmenopausal women. We performed a cross-sectional study with postmenopausal women aged 45–64 years and body mass index N 25 kg/m2, divided into physically active (n = 23) and sedentary (n = 12) groups. Mitochondria functioning and viability, bioenergetics and redox status parameters were assessed in PBMC with spectrophotometric and fluorometric assays. No differences were found in the enzyme activity of complexes I and II of the electron transport chain (ETC), mitochondrial superoxide dismutase (MnSOD) activity, methyl-tetrazolium reduction levels and reduced glutathione and oxidized glutathione levels between the groups. However, the physically active group presented higher levels of reactive oxygen species (ROS) (P= 0.04) and increased catalase (CAT) (P= 0.029), total (P= 0.011) and cytosolic SOD (CuZnSOD) (P= 0.009) activities. An active lifestyle that includes aerobic exercise for at least 30 min, three times per week may improve antioxidant enzyme activities in PBMC in overweight/obese postmenopausal women, without changes in the activity of the ETC enzymes. However, this low intensity physical activity is not able to induce relevant mitochondrial adaptations.

Melatonin attenuates postharvest physiological deterioration of cassava storage roots.

PubMed

Ma, Qiuxiang; Zhang, Ting; Zhang, Peng; Wang, Zhen-Yu

2016-05-01

Melatonin reportedly increases abiotic and biotic stress tolerance in plants, but information on its in vivo effects during postharvest physiological deterioration (PPD) in cassava is limited. In this study, we investigated the effect of melatonin in regulating cassava PPD. Treatment with 500 mg/L melatonin significantly delayed cassava PPD and reduced the accumulation of hydrogen peroxide (H2O2) while increasing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR), but not ascorbate peroxidase (APX). Transcript analysis further showed that expression of copper/zinc SOD (MeCu/ZnSOD), MeCAT1, glutathione peroxidase (MeGPX), peroxidase 3 (MePX3), and glutathione S-transferases (MeGST) was higher in cassava roots sliced treated with 500 mg/L melatonin than in those not exposed to exogenous melatonin. These data demonstrate that melatonin delays cassava PPD by directly or indirectly maintaining homoeostasis of cellular reactive oxygen species (ROS). We also found that accumulation of endogenous melatonin and the transcript levels of melatonin biosynthesis genes changed dynamically during the PPD process. This finding suggested that endogenous melatonin acts as a signal modulator for maintaining cassava PPD progression and that manipulation of melatonin biosynthesis genes through genetic engineering might prevent cassava root deterioration. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Electrodeposition of Zn and Cu-Zn alloy from ZnO/CuO precursors in deep eutectic solvent

NASA Astrophysics Data System (ADS)

Xie, Xueliang; Zou, Xingli; Lu, Xionggang; Lu, Changyuan; Cheng, Hongwei; Xu, Qian; Zhou, Zhongfu

2016-11-01

The electrodeposition of Zn and Cu-Zn alloy has been investigated in choline chloride (ChCl)/urea (1:2 molar ratio) based deep eutectic solvent (DES). Cyclic voltammetry study demonstrates that the reduction of Zn(II) to Zn is a diffusion-controlled quasi-reversible, one-step, two electrons transfer process. Chronoamperometric investigation indicates that the electrodeposition of Zn on a Cu electrode typically involves three-dimensional instantaneous nucleation with diffusion-controlled growth process. Micro/nanostructured Zn films can be obtained by controlling the electrodeposition potential and temperature. The electrodeposited Zn crystals preferentially orient parallel to the (101) plane. The Zn films electrodeposited under more positive potentials and low temperatures exhibit improved corrosion resistance in 3 wt% NaCl solution. In addition, Cu-Zn alloy films have also been electrodeposited directly from CuO-ZnO precursors in ChCl/urea-based DES. The XRD analysis indicates that the phase composition of the electrodeposited Cu-Zn alloy depends on the electrodeposition potential.

Complete transformation of ZnO and CuO nanoparticles in culture medium and lymphocyte cells during toxicity testing.

PubMed

Ivask, Angela; Scheckel, Kirk G; Kapruwan, Pankaj; Stone, Vicki; Yin, Hong; Voelcker, Nicolas H; Lombi, Enzo

2017-03-01

Here, we present evidence on complete transformation of ZnO and CuO nanoparticles, which are among the most heavily studied metal oxide particles, during 24 h in vitro toxicological testing with human T-lymphocytes. Synchrotron radiation-based X-ray absorption near edge structure (XANES) spectroscopy results revealed that Zn speciation profiles of 30 nm and 80 nm ZnO nanoparticles, and ZnSO 4 - exposed cells were almost identical with the prevailing species being Zn-cysteine. This suggests that ZnO nanoparticles are rapidly transformed during a standard in vitro toxicological assay, and are sequestered intracellularly, analogously to soluble Zn. Complete transformation of ZnO in the test conditions was further supported by almost identical Zn spectra in medium to which ZnO nanoparticles or ZnSO 4 was added. Likewise, Cu XANES spectra for CuO and CuSO 4 -exposed cells and cell culture media were similar. These results together with our observation on similar toxicological profiles of ZnO and soluble Zn, and CuO and soluble Cu, underline the importance of dissolution and subsequent transformation of ZnO and CuO nanoparticles during toxicological testing and provide evidence that the nano-specific effect of ZnO and CuO nanoparticles is negligible in this system. We strongly suggest to account for this aspect when interpreting the toxicological results of ZnO and CuO nanoparticles.

Complete transformation of ZnO and CuO nanoparticles in ...

EPA Pesticide Factsheets

Here, we present evidence on complete transformation of ZnO and CuO nanoparticles, which are among the most heavily studied metal oxide particles, during 24 h in vitro toxicological testing with human T-lymphocytes. Synchrotron radiation-based X-ray absorption near edge structure (XANES) spectroscopy results revealed that Zn speciation profiles of 30 nm and 80 nm ZnO nanoparticles, and ZnSO4- exposed cells were almost identical with the prevailing species being Zn-cysteine. This suggests that ZnO nanoparticles are rapidly transformed during a standard in vitro toxicological assay, and are sequestered intracellularly, analogously to soluble Zn. Complete transformation of ZnO in the test conditions was further supported by almost identical Zn spectra in medium to which ZnO nanoparticles or ZnSO4 was added. Likewise, Cu XANES spectra for CuO and CuSO4-exposed cells and cell culture media were similar. These results together with our observation on similar toxicological profiles of ZnO and soluble Zn, and CuO and soluble Cu, underline the importance of dissolution and subsequent transformation of ZnO and CuO nanoparticles during toxicological testing and provide evidence that the nano-specific effect of ZnO and CuO nanoparticulates is negligible in this system. We strongly suggest to account for this aspect when interpreting the toxicological results of ZnO and CuO nanoparticles. Although a number of studies have discussed the transformation of nanoparticles during

Quantifying point defects in Cu 2 ZnSn(S,Se) 4 thin films using resonant x-ray diffraction

DOE PAGES

Stone, Kevin H.; Christensen, Steven T.; Harvey, Steven P.; ...

2016-10-17

Cu 2ZnSn(S,Se)4 is an interesting, earth abundant photovoltaic material, but has suffered from low open circuit voltage. To better understand the film structure, we have measured resonant x-ray diffraction across the Cu and Zn K-edges for the device quality thin films of Cu 2ZnSnS4 (8.6% efficiency) and Cu 2ZnSn(S,Se)4 (3.5% efficiency). This approach allows for the confirmation of the underlying kesterite structure and quantification of the concentration of point defects and vacancies on the Cu, Zn, and Sn sublattices. Rietveld refinement of powder diffraction data collected at multiple energies is used to determine that there exists a high level ofmore » Cu Zn and Zn Cu defects on the 2c and 2d Wyckoff positions. We observe a significantly lower concentration of Zn Sn defects and Cu or Zn vacancies.« less

Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS.

PubMed

Watanabe, Seiji; Ilieva, Hristelina; Tamada, Hiromi; Nomura, Hanae; Komine, Okiru; Endo, Fumito; Jin, Shijie; Mancias, Pedro; Kiyama, Hiroshi; Yamanaka, Koji

2016-12-01

A homozygous mutation in the gene for sigma 1 receptor (Sig1R) is a cause of inherited juvenile amyotrophic lateral sclerosis (ALS16). Sig1R localizes to the mitochondria-associated membrane (MAM), which is an interface of mitochondria and endoplasmic reticulum. However, the role of the MAM in ALS is not fully elucidated. Here, we identified a homozygous p.L95fs mutation of Sig1R as a novel cause of ALS16. ALS-linked Sig1R variants were unstable and incapable of binding to inositol 1,4,5-triphosphate receptor type 3 (IP 3 R3). The onset of mutant Cu/Zn superoxide dismutase (SOD1)-mediated ALS disease in mice was accelerated when Sig1R was deficient. Moreover, either deficiency of Sig1R or accumulation of mutant SOD1 induced MAM disruption, resulting in mislocalization of IP 3 R3 from the MAM, calpain activation, and mitochondrial dysfunction. Our findings indicate that a loss of Sig1R function is causative for ALS16, and collapse of the MAM is a common pathomechanism in both Sig1R- and SOD1-linked ALS Furthermore, our discovery of the selective enrichment of IP 3 R3 in motor neurons suggests that integrity of the MAM is crucial for the selective vulnerability in ALS. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Comparative effects of zinc oxide nanoparticles and dissolved zinc on zebrafish embryos and eleuthero-embryos: importance of zinc ions.

PubMed

Brun, Nadja Rebecca; Lenz, Markus; Wehrli, Bernhard; Fent, Karl

2014-04-01

The increasing use of zinc oxide nanoparticles (nZnO) and their associated environmental occurrence make it necessary to assess their potential effects on aquatic organisms. Upon water contact, nZnO dissolve partially to zinc (Zn(II)). To date it is not yet completely understood, whether effects of nZnO are solely or partly due to dissolved Zn(II). Here we compare potential effects of 0.2, 1 and 5mg/L nZnO and corresponding concentrations of released Zn(II) by water soluble ZnCl2 to two development stages of zebrafish, embryos and eleuthero-embryos, by analysing expressional changes by RT-qPCR. Another objective was to assess uptake and tissue distribution of Zn(II). Laser ablation-ICP-MS analysis demonstrated that uptake and tissue distribution of Zn(II) were identical for nZnO and ZnCl2 in eleuthero-embryos. Zn(II) was found particularly in the retina/pigment layer of eyes and brain. Both nZnO and dissolved Zn(II) derived from ZnCl2 had similar inhibiting effects on hatching, and they induced similar expressional changes of target genes. At 72hours post fertilization (hpf), both nZnO and Zn(II) delayed hatching at all doses, and inhibited hatching at 1 and 5 mg/L at 96 hpf. Both nZnO and Zn(II) lead to induction of metallothionein (mt2) in both embryos and eleuthero-embryos at all concentrations. Transcripts of oxidative stress related genes cat and Cu/Zn sod were also altered. Moreover, we show for the first time that nZnO exposure results in transcriptional changes of pro-inflammatory cytokines IL-1β and TNFα. Overall, transcriptional alterations were higher in embryos than eleuthero-embryos. The similarities of the effects lead to the conclusion that effects of nZnO are mainly related to the release of Zn(II). Copyright © 2014 Elsevier B.V. All rights reserved.

Abundant defects and defect clusters in kesterite Cu2ZnSnS4 and Cu2ZnSnSe4

NASA Astrophysics Data System (ADS)

Chen, Shiyou; Wang, Lin-Wang; Walsh, Aron; Gong, Xin-Gao; Wei, Su-Huai

2013-03-01

Cu2ZnSnS4 and Cu2ZnSnSe4 are drawing intensive attention as the light-absorber materials in thin-film solar cells. A large variety of intrinsic defects can be formed in these quaternary semiconductors, which have important influence on their optical and electrical properties, and hence their photovoltaic performance. We will present our first-principles calculation study on a series of intrinsic defects and defect clusters in Cu2ZnSnS4 and Cu2ZnSnSe4, and discuss: (i) strong phase-competition between the kesterites and the coexisting secondary compounds; (ii) the dominant CuZn antisites and Cu vacancies which determine the intrinsic p-type conductivity, and their dependence on the elemental ratios; (iii) the high population of charge-compensated defect clusters (like VCu + ZnCu and 2CuZn + SnZn) and their contribution to non-stoichiometry ; (iv) the deep-level defects which act as recombination centers. Based on the calculation, we will explain the experimental observation that Cu poor and Zn rich conditions give the highest solar cell efficiency, as well as suggesting an efficiency limitation in Cu2ZnSn(S,Se)4 cells with high S composition. Supported by NSF of China, JCAP: a U.S. DOE Energy Innovation Hub, Royal Society of U.K. and EPSRC, and U.S. DOE.

New Production Routes for Medical Isotopes 64Cu and 67Cu Using Accelerator Neutrons

NASA Astrophysics Data System (ADS)

Kin, Tadahiro; Nagai, Yasuki; Iwamoto, Nobuyuki; Minato, Futoshi; Iwamoto, Osamu; Hatsukawa, Yuichi; Segawa, Mariko; Harada, Hideo; Konno, Chikara; Ochiai, Kentaro; Takakura, Kosuke

2013-03-01

We have measured the activation cross sections producing 64Cu and 67Cu, promising medical radioisotopes for molecular imaging and radioimmunotherapy, by bombarding a natural zinc sample with 14 MeV neutrons. We estimated the production yields of 64Cu and 67Cu by fast neutrons from \\text{natC(d,n) with 40 MeV 5 mA deuterons. We used the present result together with the evaluated cross section of Zn isotopes. The calculated 64Cu yield is 1.8 TBq (175 g 64Zn) for 12 h of irradiation; the yields of 67Cu by 67Zn(n,p)67Cu and 68Zn(n,x)67Cu were 249 GBq (184 g 67Zn) and 287 GBq (186 g 68Zn) at the end of 2 days of irradiation, respectively. From the results, we proposed a new route to produce 67Cu with very little radionuclide impurity via the 68Zn(n,x)67Cu reaction, and showed the 64Zn(n,p)64Cu reaction to be a promising route to produce 64Cu. Both 67Cu and 64Cu are noted to be produced using fast neutrons.

Uptake and Distribution of Soil Applied Zinc by Citrus Trees—Addressing Fertilizer Use Efficiency with 68Zn Labeling

PubMed Central

Hippler, Franz Walter Rieger; Boaretto, Rodrigo Marcelli; Quaggio, José Antônio; Boaretto, Antonio Enedi; Abreu-Junior, Cassio Hamilton; Mattos, Dirceu

2015-01-01

The zinc (Zn) supply increases the fruit yield of Citrus trees that are grown, especially in the highly weathered soils of the tropics due to the inherently low nutrient availability in the soil solution. Leaf sprays containing micronutrients are commonly applied to orchards, even though the nutrient supply via soil could be of practical value. This study aimed to evaluate the effect of Zn fertilizers that are applied to the soil surface on absorption and partitioning of the nutrient by citrus trees. A greenhouse experiment was conducted with one-year-old sweet orange trees. The plants were grown in soils with different textures (18.1 or 64.4% clay) that received 1.8 g Zn per plant, in the form of either ZnO or ZnSO4 enriched with the stable isotope 68Zn. Zinc fertilization increased the availability of the nutrient in the soil and the content in the orange trees. Greater responses were obtained when ZnSO4 was applied to the sandy loam soil due to its lower specific metal adsorption compared to that of the clay soil. The trunk and branches accumulated the most fertilizer-derived Zn (Zndff) and thus represent the major reserve organ for this nutrient in the plant. The trees recovered up to 4% of the applied Zndff. Despite this relative low recovery, the Zn requirement of the trees was met with the selected treatment based on the total leaf nutrient content and increased Cu/Zn-SOD activity in the leaves. We conclude that the efficiency of Zn fertilizers depends on the fertilizer source and the soil texture, which must be taken into account by guidelines for fruit crop fertilization via soil, in substitution or complementation of traditional foliar sprays. PMID:25751056

Uptake and distribution of soil applied zinc by citrus trees-addressing fertilizer use efficiency with 68Zn labeling.

PubMed

Hippler, Franz Walter Rieger; Boaretto, Rodrigo Marcelli; Quaggio, José Antônio; Boaretto, Antonio Enedi; Abreu-Junior, Cassio Hamilton; Mattos, Dirceu

2015-01-01

The zinc (Zn) supply increases the fruit yield of Citrus trees that are grown, especially in the highly weathered soils of the tropics due to the inherently low nutrient availability in the soil solution. Leaf sprays containing micronutrients are commonly applied to orchards, even though the nutrient supply via soil could be of practical value. This study aimed to evaluate the effect of Zn fertilizers that are applied to the soil surface on absorption and partitioning of the nutrient by citrus trees. A greenhouse experiment was conducted with one-year-old sweet orange trees. The plants were grown in soils with different textures (18.1 or 64.4% clay) that received 1.8 g Zn per plant, in the form of either ZnO or ZnSO4 enriched with the stable isotope 68Zn. Zinc fertilization increased the availability of the nutrient in the soil and the content in the orange trees. Greater responses were obtained when ZnSO4 was applied to the sandy loam soil due to its lower specific metal adsorption compared to that of the clay soil. The trunk and branches accumulated the most fertilizer-derived Zn (Zndff) and thus represent the major reserve organ for this nutrient in the plant. The trees recovered up to 4% of the applied Zndff. Despite this relative low recovery, the Zn requirement of the trees was met with the selected treatment based on the total leaf nutrient content and increased Cu/Zn-SOD activity in the leaves. We conclude that the efficiency of Zn fertilizers depends on the fertilizer source and the soil texture, which must be taken into account by guidelines for fruit crop fertilization via soil, in substitution or complementation of traditional foliar sprays.

Tuning the emission of aqueous Cu:ZnSe quantum dots to yellow light window

NASA Astrophysics Data System (ADS)

Wang, Chunlei; Hu, Zhiyang; Xu, Shuhong; Wang, Yanbin; Zhao, Zengxia; Wang, Zhuyuan; Cui, Yiping

2015-07-01

Synthesis of internally doped Cu:ZnSe QDs in an aqueous solution still suffers from narrow tunable emissions from the blue to green light window. In this work, we extended the emission window of aqueous Cu:ZnSe QDs to the yellow light window. Our results show that high solution pH, multiple injections of Zn precursors, and nucleation doping strategy are three key factors for preparing yellow emitted Cu:ZnSe QDs. All these factors can depress the reactivity of CuSe nuclei and Zn monomers, promoting ZnSe growth outside CuSe nuclei rather than form ZnSe nuclei separately. With increased ZnSe QD size, the conduction band and nearby trap state energy levels shift to higher energy sites, causing Cu:ZnSe QDs to have a much longer emission.

Stable Cu and Zn isotope ratios as tracers of sources and transport of Cu and Zn in contaminated soil

NASA Astrophysics Data System (ADS)

Bigalke, Moritz; Weyer, Stefan; Kobza, Jozef; Wilcke, Wolfgang

2010-12-01

Copper and Zn metals are produced in large quantities for different applications. During Cu production, large amounts of Cu and Zn can be released to the environment. Therefore, the surroundings of Cu smelters are frequently metal-polluted. We determined Cu and Zn concentrations and Cu and Zn stable isotope ratios (δ 65Cu, δ 66Zn) in three soils at distances of 1.1, 3.8, and 5.3 km from a Slovak Cu smelter and in smelter wastes (slag, sludge, ash) to trace sources and transport of Cu and Zn in soils. Stable isotope ratios were measured by multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS) in total digests. Soils were heavily contaminated with concentrations up to 8087 μg g -1 Cu and 2084 μg g -1 Zn in the organic horizons. The δ 65Cu values varied little (-0.12‰ to 0.36‰) in soils and most wastes and therefore no source identification was possible. In soils, Cu became isotopically lighter with increasing depth down to 0.4 m, likely because of equilibrium reactions between dissolved and adsorbed Cu species during transport of smelter-derived Cu through the soil. The δ 66Zn IRMM values were isotopically lighter in ash (-0.41‰) and organic horizons (-0.85‰ to -0.47‰) than in bedrock (-0.28‰) and slag (0.18‰) likely mainly because of kinetic fractionation during evaporation and thus allowed for separation of smelter-Zn from native Zn in soil. In particular in the organic horizons large variations in δ 66Zn values occur, probably caused by biogeochemical fractionation in the soil-plant system. In the mineral horizons, Zn isotopes showed only minor shifts to heavier δ 66Zn values with depth mainly because of the mixing of smelter-derived Zn and native Zn in the soils. In contrast to Cu, Zn isotope fractionation between dissolved and adsorbed species was probably only a minor driver in producing the observed variations in δ 66Zn values. Our results demonstrate that metal stable isotope ratios may serve as tracer of sources, vertical dislocation, and biogeochemical behavior in contaminated soil.

Electrochemical corrosion behavior, microstructure and magnetic properties of sintered Nd-Fe-B permanent magnet doped by CuZn5 powders

NASA Astrophysics Data System (ADS)

Liu, W. Q.; Wang, Z.; Sun, C.; Yue, M.; Liu, Y. Q.; Zhang, D. T.; Zhang, J. X.

2014-05-01

Nd-Fe-B permanent magnets with a small amount of CuZn5 powders doping were prepared by conventional sintered method. The effects of CuZn5 contents on magnetic properties and microstructure, electrochemical corrosion resistance of sintered Nd-Fe-B magnets were systematically studied. The results show that the magnetic properties of magnets do not have a significant variation by CuZn5 powders doping; the coercivity of magnets rises gradually, while the remanence of the magnets decreases a little with increasing of the CuZn5 amount. The CuZn5 doped magnets have more positive corrosion potential, Ecorr, and much lower corrosion current density, icorr, than the magnets without CuZn5 doping, indicating CuZn5 doping could improve the corrosion resistance. Both Zn and Cu enrich mainly into the Nd-rich phase, fully improve the wettability between the Nd-rich phase and the Nd2Fe14B phase, and repair the defects of the main phase, so the coercivity of magnets doped with CuZn5 powders rises. Such microstructure modification effectively restrains the aggressive inter-granular corrosion. As a result, the CuZn5 doped magnet possesses excellent corrosion resistance in NaCl electrolyte.

Detection of Cu2Zn5SnSe8 and Cu2Zn6SnSe9 phases in co-evaporated Cu2ZnSnSe4 thin-films

NASA Astrophysics Data System (ADS)

Schwarz, Torsten; Marques, Miguel A. L.; Botti, Silvana; Mousel, Marina; Redinger, Alex; Siebentritt, Susanne; Cojocaru-Mirédin, Oana; Raabe, Dierk; Choi, Pyuck-Pa

2015-10-01

Cu2ZnSnSe4 thin-films for photovoltaic applications are investigated using combined atom probe tomography and ab initio density functional theory. The atom probe studies reveal nano-sized grains of Cu2Zn5SnSe8 and Cu2Zn6SnSe9 composition, which cannot be assigned to any known phase reported in the literature. Both phases are considered to be metastable, as density functional theory calculations yield positive energy differences with respect to the decomposition into Cu2ZnSnSe4 and ZnSe. Among the conceivable crystal structures for both phases, a distorted zinc-blende structure shows the lowest energy, which is a few tens of meV below the energy of a wurtzite structure. A band gap of 1.1 eV is calculated for both the Cu2Zn5SnSe8 and Cu2Zn6SnSe9 phases. Possible effects of these phases on solar cell performance are discussed.

Interfacial Phenomena in Al/Al, Al/Cu, and Cu/Cu Joints Soldered Using an Al-Zn Alloy with Ag or Cu Additions

NASA Astrophysics Data System (ADS)

Pstruś, Janusz; Gancarz, Tomasz

2014-05-01

The studies of soldered joints were carried out in systems: Al/solder/Al, Al/solder/Cu, Cu/solder/Cu, where the solder was (Al-Zn)EUT, (Al-Zn)EUT with 0.5, 1.0, and 1.5 at.% of Ag and (Al-Zn)EUT with 0.5, 1.0, and 1.5 at.% of Cu addition. Brazing was performed at 500 °C for 3 min. The EDS analysis indicated that the composition of the layers starting from the Cu pad was CuZn, Cu5Zn8, and CuZn4, respectively. Wetting tests were performed at 500 °C for 3, 8, 15, and 30 min, respectively. Thickness of the layers and their kinetics of growth were measured based on the SEM micrographs. The formation of interlayers was not observed from the side of Al pads. On the contrary, dissolution of the Al substrate and migration of Al-rich particles into the bulk of the solder were observed.

Cs promoted oxidation of Zn and CuZn surfaces: a combined experimental and theoretical study

NASA Astrophysics Data System (ADS)

Chaturvedi, Sanjay; Rodriguez, JoséA.; Hrbek, Jan

1997-07-01

The interaction of O 2 with Zn, {Cs}/{Zn} and {Cs}/{CuZn} surfaces was investigated using photoemission and ab initio self-consistent-field (SCF) calculations. On zinc films, the sticking probability of O 2 is extremely low (10 -3-10 -2), and O 2 exposures in the range of 10 3 to 10 4 langmuirs are necessary to produce a significant adsorption of oxygen and the transformation of metallic zinc into zinc oxide. The presence of sub monolayer coverages of cesium enhances the oxidation rate of zinc by 2-3 orders of magnitude. In the {Cs}/{Zn} system, the alkali atom donates electrons to zinc. This charge transfer facilitates the formation of Zn→O 2 dative bonds and breaking of the OO bond. For the coadsorption of Cs and O 2 on Zn(001), the larger the electron transfer from Zn into the O 2 (1 πg) orbitals, the bigger the adsorption energy of the molecule and the elongation of the OO bond. In general, cesium does not promote the oxidation of copper. In the {Cs}/{CuZn} system, copper withdraws electrons from zinc. The presence of copper in the {Cs}/{CuZn} system inhibits the oxidation of the Zn component compared with the {Cs}/{Zn} system by lowering the electron density on the Zn atoms. After exposing the {Cs}/{CuZn} system to O 2, zinc is oxidized at a rate that is larger than that found for clean CuZn surfaces and smaller than seen in {Cs}/{Zn} surfaces. Molecular hydrogen is found to have no effect on oxidized Cu, Zn and CuZn films. However, atomic hydrogen reduces ZnO to metallic zinc and CuO to Cu 2O. In the oxidized CuZn alloy, CuO is reduced first followed by the reduction of ZnO. A comparison of the behavior of O 2/Cs/Zn and H 2O/Cs/Zn systems shows that while O 2 causes severe oxidation of Cs promoted Zn surfaces, H 2O has little or no effect.

Enzymatic and non-enzymatic comparison of two different industrial tomato (Solanum lycopersicum) varieties against drought stress.

PubMed

Çelik, Özge; Ayan, Alp; Atak, Çimen

2017-12-01

The aim of this study is to compare the tolerance mechanisms of two industrial tomato varieties (X5671R and 5MX12956) under drought stress. 14 days-old tomato seedlings were subjected to 7 days-long drought stress by withholding irrigation. The effects of stress were determined by enzymatic and non-enzymatic parameters. The physiological damages were evaluated via lipid peroxidation ratio, total protein content, relative water content, chlorophyll content and proline accumulation. Enzymatic responses were determined by biochemical analysis and electrophoresis of SOD, APX, POX and CAT enzymes. Relative water contents of X5671R and 5MX12956 varieties at 7th day of drought were decreased to 8.4 and 12.2%, respectively. Applied drought decreased all photosynthetic pigments of X5671R and 5MX12956 varieties during the treatment period significantly comparing to the Day 0 as the control. Total protein content, lipid peroxidation and proline accumulation presented increased values in both varieties in accordance with the increasing stress intensity. According to lipid peroxidation analysis, 5MX12956 tomato variety was found more drought sensitive than X5671R variety. Antioxidative enzyme activities showed increases in both varieties as a response to drought stress, although CAT and APX activities presented decrease on the 7th day of applied stress. 7 days long drought stress differentially altered POX, APX and SOD isozyme patterns. Same POX bands were observed in both varieties with different band intensities. However, main isozyme pattern differences were obtained for SOD and APX. APX1, Fe-SOD and Cu/Zn-SOD2 isozyme bands should be evaluated to define their main role in the tolerance mechanism of both tomato varieties.

Silicon-Mediated Alleviation of Aluminum Toxicity by Modulation of Al/Si Uptake and Antioxidant Performance in Ryegrass Plants.

PubMed

Pontigo, Sofía; Godoy, Karina; Jiménez, Héctor; Gutiérrez-Moraga, Ana; Mora, María de la Luz; Cartes, Paula

2017-01-01

Silicon (Si) has been well documented to alleviate aluminum (Al) toxicity in vascular plants. However, the mechanisms underlying these responses remain poorly understood. Here, we assessed the effect of Si on the modulation of Si/Al uptake and the antioxidant performance of ryegrass plants hydroponically cultivated with Al (0 and 0.2 mM) in combination with Si (0, 0.5, and 2.0 mM). Exposure to Al significantly increased Al concentration, mainly in the roots, with a consequent reduction in root growth. However, Si applied to the culture media steadily diminished the Al concentration in ryegrass, which was accompanied by an enhancement in root dry matter production. A reduced concentration of Si in plant tissues was also observed when plants were simultaneously supplied with Al and Si. Interestingly, Si transporter genes ( Lsi1 and Lsi2 ) were down-regulated in roots after Si or Al was applied alone; however, both Lsi1 and Lsi2 were up-regulated as a consequence of Si application to Al-treated plants, denoting that there is an increase in Si requirement in order to cope with Al stress in ryegrass. Whereas Al addition triggered lipid peroxidation, Si contributed to an attenuation of Al-induced oxidative stress by increasing phenols concentration and modulating the activities of superoxide dismutase (SOD), catalase, peroxidase, and ascorbate peroxidase antioxidant enzymes. Differential changes in gene expression of SOD isoforms ( Mn-SOD, Cu/Zn-SOD , and Fe-SOD ) and the profile of peroxide (H 2 O 2 ) generation were also induced by Si in Al-stressed plants. This, to the best of our knowledge, is the first study to present biochemical and molecular evidence supporting the effect of Si on the alleviation of Al toxicity in ryegrass plants.

Compositional ratio effect on the surface characteristics of CuZn thin films

NASA Astrophysics Data System (ADS)

Choi, Ahrom; Park, Juyun; Kang, Yujin; Lee, Seokhee; Kang, Yong-Cheol

2018-05-01

CuZn thin films were fabricated by RF co-sputtering method on p-type Si(100) wafer with various RF powers applied on metallic Cu and Zn targets. This paper aimed to determine the morphological, chemical, and electrical properties of the deposited CuZn thin films by utilizing a surface profiler, atomic force microscopy (AFM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy (AES), UV photoelectron spectroscopy (UPS), and a 4-point probe. The thickness of the thin films was fixed at 200 ± 8 nm and the roughness of the thin films containing Cu was smaller than pure Zn thin films. XRD studies confirmed that the preferred phase changed, and this tendency is dependent on the ratio of Cu to Zn. AES spectra indicate that the obtained thin films consisted of Cu and Zn. The high resolution XPS spectra indicate that as the content of Cu increased, the intensities of Zn2+ decreased. The work function of CuZn thin films increased from 4.87 to 5.36 eV. The conductivity of CuZn alloy thin films was higher than pure metallic thin films.

Hetero-metal cation control of CuO nanostructures and their high catalytic performance for CO oxidation

NASA Astrophysics Data System (ADS)

Huang, Hongwen; Zhang, Liqiang; Wu, Kewei; Yu, Qing; Chen, Ru; Yang, Hangsheng; Peng, Xinsheng; Ye, Zhizhen

2012-11-01

A controllable synthesis of various morphologies of CuO nanostructures with tuning by hetero-metal cations has been developed in aqueous solution at room temperature. The morphologies of CuO can be engineered from nanosheets to nanoparticles with different length ratios of the long axis to the short axis. The formation of many metal-ion complexes plays an important role in slowing the release rate of OH- and affects the reaction kinetics further. We found that the effect of hetero-metal cations on the final morphology of the CuO nanostructures was the same as that of the cooling temperature. A series of temperature-controlled experiments demonstrated this. Furthermore, among all the synthesized CuO nanostructures, the fascinating colloidal mesoporous CuO quasi-monocrystalline nanosheets prepared at 25 °C with a thickness of ca. 10 nm and large specific surface area of 80.32 m2 g-1 is investigated intensively. These CuO nanosheets demonstrate a superior catalytic activity for CO oxidation, with features of high CO conversion efficiency (47.77 mmolCO g-1CuO h-1 at 200 °C), which is close to that reported for previously investigated supported-CuO catalysts, and a low apparent activation energy Ea (53.3 kJ mol-1).A controllable synthesis of various morphologies of CuO nanostructures with tuning by hetero-metal cations has been developed in aqueous solution at room temperature. The morphologies of CuO can be engineered from nanosheets to nanoparticles with different length ratios of the long axis to the short axis. The formation of many metal-ion complexes plays an important role in slowing the release rate of OH- and affects the reaction kinetics further. We found that the effect of hetero-metal cations on the final morphology of the CuO nanostructures was the same as that of the cooling temperature. A series of temperature-controlled experiments demonstrated this. Furthermore, among all the synthesized CuO nanostructures, the fascinating colloidal mesoporous CuO quasi-monocrystalline nanosheets prepared at 25 °C with a thickness of ca. 10 nm and large specific surface area of 80.32 m2 g-1 is investigated intensively. These CuO nanosheets demonstrate a superior catalytic activity for CO oxidation, with features of high CO conversion efficiency (47.77 mmolCO g-1CuO h-1 at 200 °C), which is close to that reported for previously investigated supported-CuO catalysts, and a low apparent activation energy Ea (53.3 kJ mol-1). Electronic supplementary information (ESI) available: Raman spectrum of Zn2Cu2 prepared at 25 °C (Fig. S1); content ratios of Zn/Cu for Zn2Cu2, Zn4Cu2 and Zn6Cu2 samples prepared at 25 °C measured by ICP-MS (Table S1); representative TEM images of Cu2, Zn2Cu2, Zn4Cu2 and Zn6Cu2 samples prepared at 25 °C (Fig. S2); size distributions along two perpendicular directions for Cu2, Zn2Cu2, Zn4Cu2 and Zn6Cu2 samples prepared at 25 °C (Fig. S3); the characteristic parameters of Cu2, Zn2Cu2, Zn4Cu2 and Zn6Cu2 samples prepared at 25 °C (Table S2); the characteristic parameters of Cu2, Zn2Cu2, Zn4Cu2 and Zn6Cu2 samples prepared at 35 °C (Table S3); SEM images of Zn2Cu2 products prepared at 20 °C, 25 °C, 30 °C and 50 °C (Fig. S4); the characteristic parameters of Zn2Cu2 prepared at 20 °C, 25 °C, 30 °C and 50 °C (Table S4); pH values of Cu2, Zn2Cu2, Zn4Cu2 and Zn6Cu2 solution without adding 1.6 mmol AE aqueous solution at 25 °C (Table S5); SEM images of Ag2Cu2, Mg2Cu2, Al2Cu2 prepared at 25 °C and EDS spectrum of Al2Cu2 (Fig. S5); the characteristic parameters of Cu2, Zn2Cu2, Ag2Cu2, Mg2Cu2 and Al2Cu2 samples prepared at 25 °C (Table S6); UV-Vis spectrum of Cu2 nanosheets prepared at 25 °C (Fig. S6); photograph of the Tyndall effect for the Cu2 solution prepared at 25 °C and UV-Vis absorption changes of Evans blue solutions after filtering the 80 ml Cu2 solution products (Fig. S7); FTIR spectrum of Cu2 nanosheets prepared at 25 °C (Fig. S8); Cu2p XPS spectrum of Cu2 nanosheets prepared at 25 °C (Fig. S9); detailed reaction rates of catalytic CO oxidation at different temperatures (Table S7); XRD pattern and SEM image of Cu2 sample after 6 hours of catalytic reaction (Fig. S10); nitrogen adsorption-desorption isotherms at 77 K of Zn4Cu2 prepared at 25 °C (Fig. S11). See DOI: 10.1039/c2nr32729e

The Anti-Aging Effect of Erythropoietin via the ERK/Nrf2-ARE Pathway in Aging Rats.

PubMed

Wu, Haiqin; Zhao, Jiaxin; Chen, Mengyi; Wang, Huqing; Yao, Qingling; Fan, Jiaxin; Zhang, Meng

2017-03-01

Erythropoietin (EPO) has a neuroprotective effect and can resist aging, which most likely occur through EPO increasing the activity of antioxidant enzymes and scavenging free radicals. In this study, we verified the anti-aging function of EPO and discussed the mechanism occurring through the extracellular signal-regulated kinase (ERK)/NF-E2-related factor 2 (Nrf2)-ARE pathway. A rat model of aging was induced by the continuous subcutaneous injection of 5 % D-galactose for 6 weeks. At the beginning of the sixth week, physiological saline or EPO was administered twice per day through a lateral ventricle system for a total of 7 days. In one group, 2 μl PD98059 was administered 30 min before EPO. Learning and memory ability were analyzed with the Morris water maze system. HE staining was used to observe the morphological changes in the neurons in the hippocampus, and immunohistochemical staining as well as Western blots were carried out to detect the expression of ERK for each group of rats and the expression of phosphorylated-ERK (P-ERK), Nrf2, and superoxide dismutase (SOD). Real-Time PCR was carried out to detect the amount of Nrf2 mRNA and the KEAP1 mRNA expression. EPO can significantly improve learning and memory ability in aging rats and can provide protection against aging by improving the hippocampus morphology. Immunohistochemical staining and Western blots showed P-ERK, Nrf2, and Cu-Zn SOD decreases in aging rats compared to the normal group, while the expression for those proteins increased after EPO intervention. PD98059 inhibited the enhanced expression of P-ERK, Nrf2, and Cu-Zn SOD induced by EPO. Real-Time PCR results suggested that the trend of Nrf2mRNA expression was the same as that for the proteins, which confirmed that the enhancement occurred at the gene level. As such, EPO can significantly resist or delay aging and protect the brain by reducing oxidative stress. The most likely mechanism is that EPO can promote the ERK/Nrf2-ARE pathway in aging rats and that PD98059 can inhibit that process. These findings may facilitate further studies on the mechanism of aging and applications for the neuroprotective properties of EPO for clinical treatments.

Danio rerio embryos on Prozac - Effects on the detoxification mechanism and embryo development.

PubMed

Cunha, V; Rodrigues, P; Santos, M M; Moradas-Ferreira, P; Ferreira, M

2016-09-01

In the past decade the presence of psychopharmaceuticals, including fluoxetine (FLU), in the aquatic environment has been associated with the increasing trend in human consumption of these substances. Aquatic organisms are usually exposed to chronic low doses and, therefore, risk assessments should evaluate the effects of these compounds in non-target organisms. Teleost fish possess an array of active defence mechanisms to cope with the deleterious effects of xenobiotics. These include ABC transporters, phase I and II of cellular detoxification and oxidative stress enzymes. Hence, the present study aimed at characterising the effect of FLU on embryo development of the model teleost zebrafish (Danio rerio) concomitantly with changes in the detoxification mechanisms during early developmental phases. Embryos were exposed to different concentrations of FLU (0.0015, 0.05, 0.1, 0.5 and 0.8μM) for 80hours post fertilization. Development was screened and the impact in the transcription of key genes, i.e., abcb4, abcc1, abcc2, abcg2, cyp1a, cyp3a65, gst, sod, cat, ahr, pxr, pparα, pparβ, pparγ, rxraa, rxrab, rxrbb, rxrga, rxrgb, raraa, rarab, rarga evaluated. In addition, accumulation assays were performed to measure the activity of ABC proteins and antioxidant enzymes (CAT and Cu/ZnSOD) after exposure to FLU. Embryo development was disrupted at the lowest FLU concentration tested (0.0015μM), which is in the range of concentrations found in WWTP effluents. Embryos exposed to higher concentrations of FLU decreased Cu/Zn SOD, and increased CAT (0.0015 and 0.5μM) enzymatic activity. Exposure to higher concentrations of FLU decreased the expression of most genes belonging to the detoxification system and upregulated cat at 0.0015μM of FLU. Most of the tested concentrations downregulated pparα, pparβ, pparγ, and raraa, rxraa, rxrab, rxrbb rxrgb and ahr gene expression while pxr was significantly up regulated at all tested concentrations. In conclusion, this study shows that FLU can impact zebrafish embryo development, at concentrations found in effluents of WWTPs, concomitantly with changes in antioxidant enzymes, and the transcription of key genes involved in detoxification and development. These finding raises additional concerns supporting the need to monitor the presence of this compound in aquatic reservoirs. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of emodin on cell viability, respiratory burst and gene expression of Nrf2-Keap1 signaling molecules in the peripheral blood leukocytes of blunt snout bream (Megalobrama amblycephala).

PubMed

Zhao, Zhenxin; Xie, Jun; Liu, Bo; Ge, Xianping; Song, Changyou; Ren, Mingchun; Zhou, Qunlan; Miao, Linghong; Zhang, Huimin; Shan, Fan; Yang, Zhenfei

2017-03-01

We determined the effects of emodin on the cell viability, respiratory burst activity, mRNA levels of antioxidative enzymes (Cu-Zn SOD, CAT and NOX2), and gene expressions of the Nrf2-Keap1 signaling molecules in the peripheral blood leukocytes of blunt snout bream. Triplicate groups of cultured cells were treated with different concentrations of emodin (0.04-25 μg/ml) for 24 h. Results showed that the emodin caused a dramatic loss in cell viability, and occurred in a dose-dependent manner. Emodin exposure (1-25 μg/ml) were significantly induced the ROS generation compared to the control. The respiratory burst and NADPH oxidase activities were significantly induced at a concentration of 0.20 μg/ml, and inhibited at 25 μg/ml. Besides, mRNA levels of antioxidant enzyme genes were dramatically regulated by emodin exposure for 24 h. During low concentrations of exposure, mRNA levels of Cu-Zn SOD in the cells treated with 0.04, 0.20 μg/ml, CAT, NOX2 and Nrf2 in the cells treated with 1 μg/ml were sharply increased, respectively. Whereas, high concentrations were dramatically down-regulated the gene expressions of CAT in the cells treated with 5, 25 μg/ml and NOX2 in the cells treated with 25 μg/ml. Furthermore, sharp increase in Keap1and Bach1 expression levels were observed a dose-dependent manner. In conclusion, this study demonstrated that emodin could induce antioxidant defenses which were involved in cytotoxic activities, respiratory burst and the transcriptional regulation levels of antioxidant enzymes and Nrf2-Keap1 signaling molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genomics Study of the Exposure Effect of Gymnodinium catenatum, a Paralyzing Toxin Producer, on Crassostrea gigas' Defense System and Detoxification Genes

PubMed Central

García-Lagunas, Norma; Romero-Geraldo, Reyna; Hernández-Saavedra, Norma Y.

2013-01-01

Background Crassostrea gigas accumulates paralytic shellfish toxins (PST) associated with red tide species as Gymnodinium catenatum. Previous studies demonstrated bivalves show variable feeding responses to toxic algae at physiological level; recently, only one study has reported biochemical changes in the transcript level of the genes involved in C. gigas stress response. Principal Findings We found that 24 h feeding on toxic dinoflagellate cells (acute exposure) induced a significant decrease in clearance rate and expression level changes of the genes involved in antioxidant defense (copper/zinc superoxide dismutase, Cu/Zn-SOD), cell detoxification (glutathione S-transferase, GST and cytochrome P450, CPY450), intermediate immune response activation (lipopolysaccharide and beta glucan binding protein, LGBP), and stress responses (glutamine synthetase, GS) in Pacific oysters compared to the effects with the non-toxic microalga Isochrysis galbana. A sub-chronic exposure feeding on toxic dinoflagellate cells for seven and fourteen days (30×103 cells mL−1) showed higher gene expression levels. A significant increase was observed in Cu/Zn-SOD, GST, and LGBP at day 7 and a major increase in GS and CPY450 at day 14. We also observed that oysters fed only with G. catenatum (3×103 cells mL−1) produced a significant increase on the transcription level than in a mixed diet (3×103 cells mL−1 of G. catenatum+0.75×106 cells mL−1 I. galbana) in all the analyzed genes. Conclusions Our results provide gene expression data of PST producer dinoflagellate G. catenatum toxic effects on C. gigas, a commercially important bivalve. Over expressed genes indicate the activation of a potent protective mechanism, whose response depends on both cell concentration and exposure time against these toxic microalgae. Given the importance of dinoflagellate blooms in coastal environments, these results provide a more comprehensive overview of how oysters respond to stress generated by toxic dinoflagellate exposure. PMID:24039751

Optimization of Cu-Zn Massive Sulphide Flotation by Selective Reagents

NASA Astrophysics Data System (ADS)

Soltani, F.; Koleini, S. M. J.; Abdollahy, M.

2014-10-01

Selective floatation of base metal sulphide minerals can be achieved by using selective reagents. Sequential floatation of chalcopyrite-sphalerite from Taknar (Iran) massive sulphide ore with 3.5 % Zn and 1.26 % Cu was studied. D-optimal design of response surface methodology was used. Four mixed collector types (Aer238 + SIPX, Aero3477 + SIPX, TC1000 + SIPX and X231 + SIPX), two depressant systems (CuCN-ZnSO4 and dextrin-ZnSO4), pH and ZnSO4 dosage were considered as operational factors in the first stage of flotation. Different conditions of pH, CuSO4 dosage and SIPX dosage were studied for sphalerite flotation from first stage tailings. Aero238 + SIPX induced better selectivity for chalcopyrite against pyrite and sphalerite. Dextrin-ZnSO4 was as effective as CuCN-ZnSO4 in sphalerite-pyrite depression. Under optimum conditions, Cu recovery, Zn recovery and pyrite content in Cu concentrate were 88.99, 33.49 and 1.34 % by using Aero238 + SIPX as mixed collector, CuCN-ZnSO4 as depressant system, at ZnSO4 dosage of 200 g/t and pH 10.54. When CuCN was used at the first stage, CuSO4 consumption increased and Zn recovery decreased during the second stage. Maximum Zn recovery was 72.19 % by using 343.66 g/t of CuSO4, 22.22 g/t of SIPX and pH 9.99 at the second stage.

Synthesis of ZnO/CuO and TiO{sub 2}/CuO nanocomposites for light and ultrasound assisted degradation of a textile dye in aqueous solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muzakki, Afifah; Shabrany, Hesni; Saleh, Rosari, E-mail: rosari.saleh@gmail.com, E-mail: rosari.saleh@ui.ac.id

2016-04-19

ZnO/CuO and TiO2/CuO nanocomposites with different Zn/Cu and Ti/Cu ratios were prepared using sol-gel method. The obtained composite samples were used as catalyst. Methylene blue was used as a model of textile dye to evaluate their photocatalytic, sonocatalytic and photosonocatalytic activities. X-ray diffraction and energy dispersive X- ray analysis confirmed that only monoclinic CuO and hexagonal wurtzite ZnO structures are present in ZnO/CuO nanocomposites, while in TiO2/CuO nanocomposites monoclinic CuO and anatase TiO2 structures were observed. The degradation of methylene blue indicated that the incorporation of CuO in ZnO/CuO and TiO2/CuO nanocomposites exhibited an appreciable higher photocatalytic activity, which wasmore » mainly attributed to the extended photoresponding range and more light energy could be utilized than pure ZnO and TiO2.« less

Survey of Nuclear Activations for Intense Proton and Deuteron Beams

DTIC Science & Technology

1992-12-24

1.115 64Zn(d,t)6𔃽 Zn -5.60 ÷ 38 min 2.34 0.51 64Zn(d,a)’ 2 Cu 7.52 ÷ 9.8 min 2.93 0.51 6’Zn(d,2p) 64Cu -2.01 - 12.8 hr 0.575 - c,o+ 12.8 hr 0.656...and for the activation of 5aCo by deuterons on a natural nickel target. 43 THICK-TARGET YIELDS Copper Target 1000 63Cu(d,p) 64Cu 65Cu(d,p)66Cu o 100 6...activation of 1 5 Zn by deuterons and for the GCZn(d,n)"Ga, ’,IZn(d,p)60 Zn, 6SZn(d,p)69mZn, 6 6 Zn(d,(X) 64Cu , and 68Zn(d,2n)6,8Ga reactions in a natural zinc target. 45

Variation in copper and zinc tolerance and accumulation in 12 willow clones: implications for phytoextraction*

PubMed Central

Yang, Wei-dong; Wang, Yu-yan; Zhao, Feng-liang; Ding, Zhe-li; Zhang, Xin-cheng; Zhu, Zhi-qiang; Yang, Xiao-e

2014-01-01

Willows (Salix spp.) have shown high potential for the phytoextraction of heavy metals. This study compares variations in copper (Cu) and zinc (Zn) tolerance and accumulation potential among 12 willow clones grown in a nutrient solution treated with 50 μmol/L of Cu or Zn, respectively. The results showed differences in the tolerance and accumulation of Cu and Zn with respect to different species/clones. The biomass variation among clones in response to Cu or Zn exposure ranged from the stimulation of growth to inhibition, and all of the clones tested showed higher tolerance to Cu than to Zn. The clones exhibited less variation in Cu accumulation but larger variation in Zn accumulation. Based on translocation factors, it was found that most of the Cu was retained in the roots and that Zn was more mobile than Cu for all clones. It is concluded that most willow clones are good accumulators of Zn and Cu. PMID:25183033

Electrodeposition of CuZn Alloys from the Non-Cyanide Alkaline Baths

NASA Astrophysics Data System (ADS)

Li, Minggang; Wei, Guoying; Hu, Shuangshuang; Xu, Shuhan; Yang, Yejiong; Miao, Qinfang

2015-10-01

Effect of copper sulfate on CuZn alloys electroplating from non-cyanide baths are investigated by different electrochemical methods. Cyclic voltammetry and current transient measurements are used to characterize the CuZn alloys electroplating system in order to analyze the nucleation and growth mechanism. The reduction of Cu and CuZn alloy on sheet iron substrates shows an instantaneous nucleation process. However, the reduction of Zn on sheet iron substrates shows a progressive nucleation process. The structure and surface morphology of CuZn alloys are analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The morphology of CuZn alloys obtained with 50 g L-1 copper sulfate presents a smooth and compact deposit and the size of crystal particle is uniform.

Colloidal synthesis of Cu-ZnO and Cu@CuNi-ZnO hybrid nanocrystals with controlled morphologies and multifunctional properties

NASA Astrophysics Data System (ADS)

Zeng, Deqian; Gong, Pingyun; Chen, Yuanzhi; Zhang, Qinfu; Xie, Qingshui; Peng, Dong-Liang

2016-06-01

Metal-semiconductor hybrid nanocrystals have received extensive attention owing to their multiple functionalities which can find wide technological applications. The utilization of low-cost non-noble metals to construct novel metal-semiconductor hybrid nanocrystals is important and meaningful for their large-scale applications. In this study, a facile solution approach is developed for the synthesis of Cu-ZnO hybrid nanocrystals with well-controlled morphologies, including nanomultipods, core-shell nanoparticles, nanopyramids and core-shell nanowires. In the synthetic strategy, Cu nanocrystals formed in situ serve as seeds for the heterogeneous nucleation and growth of ZnO, and it eventually forms various Cu-ZnO hetero-nanostructures under different reaction conditions. These hybrid nanocrystals possess well-defined and stable heterostructure junctions. The ultraviolet-visible-near infrared spectra reveal morphology-dependent surface plasmon resonance absorption of Cu and the band gap absorption of ZnO. Furthermore, we construct a novel Cu@CuNi-ZnO ternary hetero-nanostructure by incorporating the magnetic metal Ni into the pre-synthesized colloidal Cu nanocrystals. Such hybrid nanocrystals possess a magnetic Cu-Ni intermediate layer between the ZnO shell and the Cu core, and exhibit ferromagnetic/superparamagnetic properties which expand their functionalities. Finally, enhanced photocatalytic activities are observed in the as-prepared non-noble metal-ZnO hybrid nanocrystals. This study not only provides an economical way to prepare high-quality morphology-controlled Cu-ZnO hybrid nanocrystals for potential applications in the fields of photocatalysis and photovoltaic devices, but also opens up new opportunities in designing ternary non-noble metal-semiconductor hybrid nanocrystals with multifunctionalities.Metal-semiconductor hybrid nanocrystals have received extensive attention owing to their multiple functionalities which can find wide technological applications. The utilization of low-cost non-noble metals to construct novel metal-semiconductor hybrid nanocrystals is important and meaningful for their large-scale applications. In this study, a facile solution approach is developed for the synthesis of Cu-ZnO hybrid nanocrystals with well-controlled morphologies, including nanomultipods, core-shell nanoparticles, nanopyramids and core-shell nanowires. In the synthetic strategy, Cu nanocrystals formed in situ serve as seeds for the heterogeneous nucleation and growth of ZnO, and it eventually forms various Cu-ZnO hetero-nanostructures under different reaction conditions. These hybrid nanocrystals possess well-defined and stable heterostructure junctions. The ultraviolet-visible-near infrared spectra reveal morphology-dependent surface plasmon resonance absorption of Cu and the band gap absorption of ZnO. Furthermore, we construct a novel Cu@CuNi-ZnO ternary hetero-nanostructure by incorporating the magnetic metal Ni into the pre-synthesized colloidal Cu nanocrystals. Such hybrid nanocrystals possess a magnetic Cu-Ni intermediate layer between the ZnO shell and the Cu core, and exhibit ferromagnetic/superparamagnetic properties which expand their functionalities. Finally, enhanced photocatalytic activities are observed in the as-prepared non-noble metal-ZnO hybrid nanocrystals. This study not only provides an economical way to prepare high-quality morphology-controlled Cu-ZnO hybrid nanocrystals for potential applications in the fields of photocatalysis and photovoltaic devices, but also opens up new opportunities in designing ternary non-noble metal-semiconductor hybrid nanocrystals with multifunctionalities. Electronic supplementary information (ESI) available: Synthesis and TEM images of pure ZnO nanocrystals. Photocatalytic testing procedures and degradation curves. SEM and TEM images, SAED pattern and EDS spectra and maps of parts of Cu-ZnO hybrid samples. A schematic image of coincident lattice matching between Cu and ZnO. STEM-EDS elemental maps and XRD pattern of the Cu@CuNi-ZnO sample. Comparative synthetic parameters. See DOI: 10.1039/c6nr02055k

Effects of dietary zinc, iron, and copper in layer feed on distribution of these elements in eggs, liver, excreta, soil, and herbage.

PubMed

Skrivan, M; Skrivanová, V; Marounek, M

2005-10-01

An experiment was conducted to evaluate the effect of dietary content and combinations of Zn, Fe, and Cu on deposition of these elements in egg components, liver, and excreta. Excreta were applied as a manure to a lawn, and 3 mo later soil and herbage samples were taken and analyzed. The experiment comprised 144 hens in 8 groups. The basal diet contained Zn, Fe, and Cu at 63.4, 92.8, and 9.0 mg/kg, respectively. It was supplemented with 1, 2, or 3 trace elements (inorganic forms) at 80 mg of Zn/kg, 120 mg of Fe/kg, and 25 mg of Cu/kg. Recovery of Zn, Fe, and Cu in eggs of hens fed the basal diet was 10.7, 9.8, and 4.4% of the alimentary intake, respectively. A Zn-Cu antagonism was observed; deposition of Zn in the yolk was significantly decreased by Cu addition and vice versa (P < 0.01). Supplementation of the basal diet with Fe increased Fe concentration in egg yolk and white by 6.3 and 2.2%, respectively. The combination of Fe with Zn and Cu, however, increased Fe concentration in the yolk and white by 36.7 and 34.9%, respectively (P < 0.01). The enrichment of eggs with the other elements was marginal (Cu) or absent (Zn). Effects of Zn, Fe, and Cu of the basal diet on liver concentrations of these elements were relatively small, and no antagonism between Zn and Cu was apparent. Supplementation of the basal diet with the combination of Zn and Fe, however, significantly decreased hepatic concentration of Cu. On the other hand, Cu supplementation significantly increased Fe concentration in livers of hens fed the Fe-supplemented diet (P < 0.01). Concentrations of Zn, Fe, and Cu in excreta were related to their dietary content. High concentrations of Zn, Fe, and Cu in excreta corresponded with limited deposition of the 3 elements in eggs and liver. Concentrations of Zn, Fe, and Cu in herbage correlated significantly with the supply of these elements by hen excreta into soil. The Zn supplied by hen excreta was more stable than Fe and Cu; thus Zn could accumulate in the soil.

Structural and elemental characterization of high efficiency Cu2ZnSnS4 solar cells

NASA Astrophysics Data System (ADS)

Wang, Kejia; Shin, Byungha; Reuter, Kathleen B.; Todorov, Teodor; Mitzi, David B.; Guha, Supratik

2011-01-01

We have carried out detailed microstructural studies of phase separation and grain boundary composition in Cu2ZnSnS4 based solar cells. The absorber layer was fabricated by thermal evaporation followed by post high temperature annealing on hot plate. We show that inter-reactions between the bottom molybdenum and the Cu2ZnSnS4, besides triggering the formation of interfacial MoSx, results in the out-diffusion of Cu from the Cu2ZnSnS4 layer. Phase separation of Cu2ZnSnS4 into ZnS and a Cu-Sn-S compound is observed at the molybdenum-Cu2ZnSnS4 interface, perhaps as a result of the compositional out-diffusion. Additionally, grain boundaries within the thermally evaporated absorber layer are found to be either Cu-rich or at the expected bulk composition. Such interfacial compound formation and grain boundary chemistry likely contributes to the lower than expected open circuit voltages observed for the Cu2ZnSnS4 devices.

Hydrogenation of CO 2 on ZnO/Cu(100) and ZnO/Cu(111) Catalysts: Role of Copper Structure and Metal–Oxide Interface in Methanol Synthesis

DOE PAGES

Palomino, Robert M.; Ramirez, Pedro J.; Liu, Zongyuan; ...

2017-08-21

The results of kinetic tests and ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) show the important role played by a ZnO–copper interface in the generation of CO and the synthesis of methanol from CO 2 hydrogenation. The deposition of nanoparticles of ZnO on Cu(100) and Cu(111), θ oxi < 0.3 monolayer, produces highly active catalysts. The catalytic activity of these systems increases in the sequence: Cu(111) < Cu(100) < ZnO/Cu(111) < ZnO/Cu(100). The structure of the copper substrate influences the catalytic performance of a ZnO–copper interface. Furthermore, size and metal–oxide interactions affect the chemical and catalytic properties of the oxide making themore » supported nanoparticles different from bulk ZnO. The formation of a ZnO–copper interface favors the binding and conversion of CO 2 into a formate intermediate that is stable on the catalyst surface up to temperatures above 500 K. Alloys of Zn with Cu(111) and Cu(100) were not stable at the elevated temperatures (500–600 K) used for the CO 2 hydrogenation reaction. However, reaction with CO 2 oxidized the zinc, enhancing its stability over the copper substrates.« less

Hydrogenation of CO 2 on ZnO/Cu(100) and ZnO/Cu(111) Catalysts: Role of Copper Structure and Metal–Oxide Interface in Methanol Synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palomino, Robert M.; Ramirez, Pedro J.; Liu, Zongyuan

The results of kinetic tests and ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) show the important role played by a ZnO–copper interface in the generation of CO and the synthesis of methanol from CO 2 hydrogenation. The deposition of nanoparticles of ZnO on Cu(100) and Cu(111), θ oxi < 0.3 monolayer, produces highly active catalysts. The catalytic activity of these systems increases in the sequence: Cu(111) < Cu(100) < ZnO/Cu(111) < ZnO/Cu(100). The structure of the copper substrate influences the catalytic performance of a ZnO–copper interface. Furthermore, size and metal–oxide interactions affect the chemical and catalytic properties of the oxide making themore » supported nanoparticles different from bulk ZnO. The formation of a ZnO–copper interface favors the binding and conversion of CO 2 into a formate intermediate that is stable on the catalyst surface up to temperatures above 500 K. Alloys of Zn with Cu(111) and Cu(100) were not stable at the elevated temperatures (500–600 K) used for the CO 2 hydrogenation reaction. However, reaction with CO 2 oxidized the zinc, enhancing its stability over the copper substrates.« less

Effects of swift heavy ion irradiation on structural, optical and photocatalytic properties of ZnO–CuO nanocomposites prepared by carbothermal evaporation method

PubMed Central

Kuriakose, Sini; Avasthi, D K

2015-01-01

Summary ZnO–CuO nanocomposite thin films were prepared by carbothermal evaporation of ZnO and Cu, combined with annealing. The effects of 90 MeV Ni7+ ion irradiation on the structural and optical properties of ZnO–CuO nanocomposites were studied by using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), UV–visible absorption spectroscopy and Raman spectroscopy. XRD studies showed the presence of ZnO and CuO nanostructures in the nanocomposites. FESEM images revealed the presence of nanosheets and nanorods in the nanocomposites. The photocatalytic activity of ZnO–CuO nanocomposites was evaluated on the basis of degradation of methylene blue (MB) and methyl orange (MO) dyes under sun light irradiation and it was observed that swift heavy ion irradiation results in significant enhancement in the photocatalytic efficiency of ZnO–CuO nanocomposites towards degradation of MB and MO dyes. The possible mechanism for the enhanced photocatalytic activity of ZnO–CuO nanocomposites is proposed. We attribute the observed enhanced photocatalytic activity of ZnO–CuO nanocomposites to the combined effects of improved sun light utilization and suppression of the recombination of photogenerated charge carriers in ZnO–CuO nanocomposites. PMID:25977864

Insight into the structure and mechanism of nickel-containing superoxide dismutase derived from peptide-based mimics.

PubMed

Shearer, Jason

2014-08-19

Nickel superoxide dismutase (NiSOD) is a nickel-containing metalloenzyme that catalyzes the disproportionation of superoxide through a ping-pong mechanism that relies on accessing reduced Ni(II) and oxidized Ni(III) oxidation states. NiSOD is the most recently discovered SOD. Unlike the other known SODs (MnSOD, FeSOD, and (CuZn)SOD), which utilize "typical" biological nitrogen and oxygen donors, NiSOD utilizes a rather unexpected ligand set. In the reduced Ni(II) oxidation state, NiSOD utilizes nitrogen ligands derived from the N-terminal amine and an amidate along with two cysteinates sulfur donors. These are unusual biological ligands, especially for an SOD: amine and amidate donors are underrepresented as biological ligands, whereas cysteinates are highly susceptible to oxidative damage. An axial histidine imidazole binds to nickel upon oxidation to Ni(III). This bond is long (2.3-2.6 Å) owing to a tight hydrogen-bonding network. All of the ligating residues to Ni(II) and Ni(III) are found within the first 6 residues from the NiSOD N-terminus. Thus, small nickel-containing metallopeptides derived from the first 6-12 residues of the NiSOD sequence can reproduce many of the properties of NiSOD itself. Using these nickel-containing metallopeptide-based NiSOD mimics, we have shown that the minimal sequence needed for nickel binding and reproduction of the structural, spectroscopic, and functional properties of NiSOD is H2N-HCXXPC. Insight into how NiSOD avoids oxidative damage has also been gained. Using small NiN2S2 complexes and metallopeptide-based mimics, it was shown that the unusual nitrogen donor atoms protect the cysteinates from oxidative damage (both one-electron oxidation and oxygen atom insertion reactions) by fine-tuning the electronic structure of the nickel center. Changing the nitrogen donor set to a bis-amidate or bis-amine nitrogen donor led to catalytically nonviable species owing to nickel-cysteinate bond oxidative damage. Only the amine/amidate nitrogen donor atoms within the NiSOD ligand set produce a catalytically viable species. These metallopeptide-based mimics have also hinted at the detailed mechanism of SOD catalysis by NiSOD. One such aspect is that the axial imidazole likely remains ligated to the Ni center under rapid catalytic conditions (i.e., high superoxide loads). This reduces the degree of structural rearrangement about the nickel center, leading to higher catalytic rates. Metallopeptide-based mimics have also shown that, although an axial ligand to Ni(III) is required for catalysis, the rates are highest when this is a weak interaction, suggesting a reason for the long axial His-Ni(III) bond found in NiSOD. These mimics have also suggested a surprising mechanistic insight: O2(-) reduction via a "H(•)" tunneling event from a R-S(H(+))-Ni(II) moiety to O2(-) is possible. The importance of this mechanism in NiSOD has not been verified.

Intrinsic point defects in off-stoichiometric Cu2ZnSnSe4: A neutron diffraction study

NASA Astrophysics Data System (ADS)

Gurieva, Galina; Valle Rios, Laura Elisa; Franz, Alexandra; Whitfield, Pamela; Schorr, Susan

2018-04-01

This work is an experimental study of intrinsic point defects in off-stoichiometric kesterite type CZTSe by means of neutron powder diffraction. We revealed the existence of copper vacancies (VCu), various cation anti site defects (CuZn, ZnCu, ZnSn, SnZn, and CuZn), as well as interstitials (Cui, Zni) in a wide range of off-stoichiometric polycrystalline powder samples synthesized by the solid state reaction. The results show that the point defects present in off-stoichiometric CZTSe agree with the off-stoichiometry type model, assuming certain cation substitutions accounting for charge balance. In addition to the known off-stoichiometry types A-H, new types (I-L) have been introduced. For the very first time, a correlation between the chemical composition of the CZTSe kesterite type phase and the occurring intrinsic point defects is presented. In addition to the off-stoichiometry type specific defects, the Cu/Zn disorder is always present in the CZTSe phase. In Cu-poor/Zn-rich CZTSe, a composition considered as the one that delivers the best photovoltaic performance, mainly copper vacancies, ZnCu and ZnSn anti sites are present. Also, this compositional region shows the lowest degree of Cu/Zn disorder.

Effects of CuZnAl Particles on Properties and Microstructure of Sn-58Bi Solder

PubMed Central

Yang, Fan; Zhang, Liang; Liu, Zhi-quan; Zhong, Su Juan; Ma, Jia; Bao, Li

2017-01-01

With the purpose of improving the properties of the Sn-58Bi lead-free solder, micro-CuZnAl particles ranging from 0 to 0.4 wt % were added into the low temperature eutectic Sn-58Bi lead-free solder. After the experimental testing of micro-CuZnAl particles on the properties and microstructure of the Sn-58Bi solders, it was found that the wettability of the Sn-58Bi solders was obviously improved with addition of CuZnAl particles. When the addition of CuZnAl particles was 0.2 wt %, the wettability of the Sn-58Bi solder performed best. At the same time, excessive addition of CuZnAl particles led to poor wettability. However, the results showed that CuZnAl particles changed the melting point of the Sn-58Bi solder slightly. The microstructure of the Sn-58Bi solder was refined by adding CuZnAl particles. When the content of CuZnAl addition was between 0.1 and 0.2 wt %, the refinement was great. In addition, the interfacial IMC layer between new composite solder and Cu substrate was thinner than that between the Sn-58Bi solder and Cu substrate. PMID:28772917

Phytotoxic effects of Cu and Zn on soybeans grown in field-aged soils: their additive and interactive actions.

PubMed

Kim, Bojeong; McBride, Murray B

2009-01-01

A field pot experiment was conducted to investigate the interactive phytotoxicity of soil Cu and Zn on soybean plants [Glycine max (L.) Merr.]. Two soils (Arkport sandy loam [coarse-loamy, mixed, active, mesic Lamellic Hapludalf] and Hudson silty clay loam [fine, illitic, mesic Glossaquic Hapludalf]) spiked with Cu, Zn, and combinations of both to reach the final soil metal range of 0 to 400 mg kg(-1) were tested in a 2-yr bioassay after 1 yr of soil-metal equilibration in the field. The soluble and easily-extractable fraction of soil Zn (or Cu), estimated by dilute CaCl2, increased linearly in response to the total Zn (or Cu) added. This linearity was, however, strongly affected where soils were treated with both metals in combination, most notably for Zn, as approximately 50% more of soil Zn was extracted into solution when the Cu level was high. Consequently, added Zn is less likely to be stabilized by aging than added Cu when both metals are present in field soils. The predictive model relating soil metal extractability to plant Zn concentration also revealed a significant Cu-Zn interaction. By contrast, the interaction between the two metals contributed little to explain plant Cu uptake. The additive action of soil Cu and Zn was of considerable importance in explaining plant biomass reduction. This work clearly demonstrates the critical roles of the properties of the soil, the nature of the metal, and the level of other toxic metals present on the development of differential phytotoxicity due to soil Cu and Zn.

Fractionation of Cu and Zn isotopes during adsorption onto amorphous Fe(III) oxyhydroxide: Experimental mixing of acid rock drainage and ambient river water

USGS Publications Warehouse

Balistrieri, L.S.; Borrok, D.M.; Wanty, R.B.; Ridley, W.I.

2008-01-01

Fractionation of Cu and Zn isotopes during adsorption onto amorphous ferric oxyhydroxide is examined in experimental mixtures of metal-rich acid rock drainage and relatively pure river water and during batch adsorption experiments using synthetic ferrihydrite. A diverse set of Cu- and Zn-bearing solutions was examined, including natural waters, complex synthetic acid rock drainage, and simple NaNO3 electrolyte. Metal adsorption data are combined with isotopic measurements of dissolved Cu (65Cu/63Cu) and Zn (66Zn/64Zn) in each of the experiments. Fractionation of Cu and Zn isotopes occurs during adsorption of the metal onto amorphous ferric oxyhydroxide. The adsorption data are modeled successfully using the diffuse double layer model in PHREEQC. The isotopic data are best described by a closed system, equilibrium exchange model. The fractionation factors (??soln-solid) are 0.99927 ?? 0.00008 for Cu and 0.99948 ?? 0.00004 for Zn or, alternately, the separation factors (??soln-solid) are -0.73 ?? 0.08??? for Cu and -0.52 ?? 0.04??? for Zn. These factors indicate that the heavier isotope preferentially adsorbs onto the oxyhydroxide surface, which is consistent with shorter metal-oxygen bonds and lower coordination number for the metal at the surface relative to the aqueous ion. Fractionation of Cu isotopes also is greater than that for Zn isotopes. Limited isotopic data for adsorption of Cu, Fe(II), and Zn onto amorphous ferric oxyhydroxide suggest that isotopic fractionation is related to the intrinsic equilibrium constants that define aqueous metal interactions with oxyhydroxide surface sites. Greater isotopic fractionation occurs with stronger metal binding by the oxyhydroxide with Cu > Zn > Fe(II).

Chemical fractionation of Cu and Zn in stormwater, roadway dust and stormwater pond sediments

USGS Publications Warehouse

Camponelli, Kimberly M.; Lev, Steven M.; Snodgrass, Joel W.; Landa, Edward R.; Casey, Ryan E.

2010-01-01

This study evaluated the chemical fractionation of Cu and Zn from source to deposition in a stormwater system. Cu and Zn concentrations and chemical fractionation were determined for roadway dust, roadway runoff and pond sediments. Stormwater Cu and Zn concentrations were used to generate cumulative frequency distributions to characterize potential exposure to pond-dwelling organisms. Dissolved stormwater Zn exceeded USEPA acute and chronic water quality criteria in approximately 20% of storm samples and 20% of the storm duration sampled. Dissolved Cu exceeded the previously published chronic criterion in 75% of storm samples and duration and exceeded the acute criterion in 45% of samples and duration. The majority of sediment Cu (92–98%) occurred in the most recalcitrant phase, suggesting low bioavailability; Zn was substantially more available (39–62% recalcitrant). Most sediment concentrations for Cu and Zn exceeded published threshold effect concentrations and Zn often exceeded probable effect concentrations in surface sediments.

A facile green antisolvent approach to Cu2+-doped ZnO nanocrystals with visible-light-responsive photoactivities.

PubMed

Lu, Yi-Hsuan; Lin, Wei-Hao; Yang, Chao-Yao; Chiu, Yi-Hsuan; Pu, Ying-Chih; Lee, Min-Han; Tseng, Yuan-Chieh; Hsu, Yung-Jung

2014-08-07

An environmentally benign antisolvent method has been developed to prepare Cu(2+)-doped ZnO nanocrystals with controllable dopant concentrations. A room temperature ionic liquid, known as a deep eutectic solvent (DES), was used as the solvent to dissolve ZnO powders. Upon the introduction of the ZnO-containing DES into a bad solvent which shows no solvation to ZnO, ZnO was precipitated and grown due to the dramatic decrease of solubility. By adding Cu(2+) ions to the bad solvent, the growth of ZnO from the antisolvent process was accompanied by Cu(2+) introduction, resulting in the formation of Cu(2+)-doped ZnO nanocrystals. The as-prepared Cu(2+)-doped ZnO showed an additional absorption band in the visible range (400-800 nm), which conduced to an improvement in the overall photon harvesting efficiency. Time-resolved photoluminescence spectra, together with the photovoltage information, suggested that the doped Cu(2+) may otherwise trap photoexcited electrons during the charge transfer process, inevitably depressing the photoconversion efficiency. The photoactivity of Cu(2+)-doped ZnO nanocrystals for photoelectrochemical water oxidation was effectively enhanced in the visible region, which achieved the highest at 2.0 at% of Cu(2+). A further increase in the Cu(2+) concentration however led to a decrease in the photocatalytic performance, which was ascribed to the significant carrier trapping caused by the increased states given by excessive Cu(2+). The photocurrent action spectra illustrated that the enhanced photoactivity of the Cu(2+)-doped ZnO nanocrystals was mainly due to the improved visible photon harvesting achieved by Cu(2+) doping. These results may facilitate the use of transition metal ion-doped ZnO in other photoconversion applications, such as ZnO based dye-sensitized solar cells and magnetism-assisted photocatalytic systems.

Synergistic Effects of Apigenin and Paclitaxel on Apoptosis of Cancer Cells

PubMed Central

Diao, Ying; Lu, Changyan; Fu, Jin; Luo, Lan; Yin, Zhimin

2011-01-01

Background It was well known that the clinical use of chemotherapeutic drugs is restricted by severe adverse reactions and drug resistances. Thus it is necessary to figure out a strategy to increase the specific anti-tumor efficiency of chemotherapeutic drugs. Apigenin, a kind of flavonoids, has been reported to possess anticancer activities with very low cytotoxicity to normal tissue. Methodology/Principal Findings Our results from cell viability assay, western-blots and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay demonstrated the synergistic pro-apoptotic effects of a low dose of apigenin and paclitaxel in human cancer cell lines. To analyze the underlying mechanism, we examined reactive oxygen species (ROS) staining after cells were treated with a combination of apigenin and paclitaxel, or each of them alone. Data from flow-cytometry showed that superoxides but not reduction of peroxides accumulated in HeLa cells treated with apigenin or a combination of apigenin and paclitaxel. Apigenin and paclitaxel-induced HeLa cell apoptosis was related to the level of ROS in cells. We further evaluated activity and protein level of superoxide dismutase (SOD). Apigenin significantly inhibited SOD activity but did not alter the SOD protein level suggesting that apigenin promoted ROS accumulation through suppressing enzyme activity of SOD. Addition of Zn2+, Cu2+ and Mn2+ to cell lysates inhibited apigenin's effects on SOD activity. At the same time, data from caspase-2 over-expression and knocked-down experiments demonstrated that caspase-2 participated in apigenin and paclitaxel-induced HeLa cell apoptosis. Conclusions/Significance Taken together, our study demonstrated that apigenin can sensitize cancer cells to paclitaxel induced apoptosis through suppressing SOD activity, which then led to accumulation of ROS and cleavage of caspase-2, suggesting that the combined use of apigenin and paclitaxel was an effective way to decrease the dose of paclitaxel taken. PMID:22216199

Impaired zinc and copper status in children with burn injuries: need to reassess nutritional requirements.

PubMed

Voruganti, V Saroja; Klein, Gordon L; Lu, Hong-Xing; Thomas, Suchmor; Freeland-Graves, Jeanne H; Herndon, David N

2005-09-01

Major burns are associated with impaired Zn and Cu status. These micronutrients are essential for bone matrix formation, linear growth, and wound healing. This study evaluated the status of Zn and Cu in burned children and assessed adequacy of supplementation. Six children, mean total body surface area (TBSA), 54+/-9% (S.D.), were recruited. Nutrient intakes, plasma, wound exudate, and 24h urine samples were collected and analyzed for Zn and Cu. Bone mineral content was assessed by dual energy X-ray absorptiometry. Dietary Zn and Cu were three times the dietary reference, and mean plasma concentrations of Zn and Cu were low at admission and discharge. Urinary Zn was elevated at admission, whereas Cu was elevated at both times. Wound Zn and Cu concentrations exceeded plasma concentrations, suggesting that inflammatory wound exudate was a primary route of loss. We demonstrate that burn injury in children results in low plasma levels of Zn and Cu that are inadequately compensated during hospitalization.

Near room temperature and large-area synthesis of ZnO/Cu2O heterojunction for photocatalytic properties

NASA Astrophysics Data System (ADS)

Gao, Shiyong; Zhang, Jiejing; Li, Wenqiang; Jiao, Shujie; Nie, Yanguang; Fan, Huaiyun; Zeng, Zhi; Yu, Qingjiang; Wang, Jinzhong; Zhang, Xitian

2018-01-01

Large-area ZnO/Cu2O heterojunction have been successfully synthesized on Cu foil through a simple two-step solution method at near room temperature. The field emission scanning electron microscopy characterization indicates that the morphology of as-prepared Cu2O film grown on Cu foil is octahedral structure with diameter of ∼450 nm and ZnO is nanorod arrays structure with diameter of ∼150 nm. The current-voltage measurement of ZnO/Cu2O heterojunction shows a typical rectifying characteristics. Moreover, the photocatalytic test indicates that ZnO/Cu2O heterojunction exhibits high photocatalytic efficient for degradation of congo red dyes. The possible photocatalytic mechanism of ZnO/Cu2O heterojunction is also presented.

Copper(II) and zinc(II) dinuclear enzymes model compounds: The nature of the metal ion in the biological function

NASA Astrophysics Data System (ADS)

Ferraresso, L. G.; de Arruda, E. G. R.; de Moraes, T. P. L.; Fazzi, R. B.; Da Costa Ferreira, A. M.; Abbehausen, C.

2017-12-01

First series transition metals are used abundantly by nature to perform catalytic transformations of several substrates. Furthermore, the cooperative activity of two proximal metal ions is common and represents a highly efficient catalytic system in living organisms. In this work three dinuclear μ-phenolate bridged metal complexes were prepared with copper(II) and zinc(II), resulting in a ZnZn, CuCu and CuZn with the ligand 2-ethylaminodimethylamino phenol (saldman) as model compounds of superoxide dismutase (CuCu and CuZn) and metallo-β-lactamases (ZnZn). Metals are coordinated in a μ-phenolate bridged symmetric system. Cu(II) presents a more distorted structure, while zinc is very symmetric. For this reason, [CuCu(saldman)] shows higher water solubility and also higher lability of the bridge. The antioxidant and hydrolytic beta-lactamase-like activity of the complexes were evaluated. The lability of the bridge seems to be important for the antioxidant activity and is suggested to because of [CuCu(saldman)] presents a lower antioxidant capacity than [CuZn(saldman)], which showed to present a more stable bridge in solution. The hydrolytic activity of the bimetallic complexes was assayed using nitrocefin as substrate and showed [ZnZn(saldman)] as a better catalyst than the Cu(II) analog. The series demonstrates the importance of the nature of the metal center for the biological function and how the reactivity of the model complex can be modulated by coordination chemistry.

Cu-Doped ZnO Thin Films Grown by Co-deposition Using Pulsed Laser Deposition for ZnO and Radio Frequency Sputtering for Cu

NASA Astrophysics Data System (ADS)

Shin, Hyun Wook; Son, Jong Yeog

2018-05-01

Cu-doped ZnO (CZO) thin films were fabricated on single-crystalline (0001) Al2O3 substrates by co-deposition using pulsed laser deposition for ZnO and radio frequency sputtering for Cu. CZO thin films with 0-20% molar concentrations are obtained by adjusting the deposition rates of ZnO and Cu. The CZO thin films exhibit room temperature ferromagnetism, and CZO with 5% Cu molar concentration has maximum remanent magnetization, which is consistent with theoretical results.

Toxic effects of heavy metal Cu2+ on the pacific oyster Crassostrea gigas

NASA Astrophysics Data System (ADS)

Gao, Ceng; Zhang, Xinxin; Li, Xiumei; Tang, Xuexi

2017-05-01

The effects of different concentrations of heavy metal ions on the survival of the Pacific oyster Crassostrea gigas were studied by using experimental ecology method in 96 h. The results showed that the LC50 of copper ion was 21.748mg/L and the safe concentration was 2.1748mg/L mg/L. Under the condition of laboratory, under laboratory conditions, the research of Cu2+ Stress on the C. gigas gill and digestive gland and adductor muscle tissue SOD, GPx and the induction of CAT activity. The results showed that the activities of SOD, GPx and CAT in the C. gigas were significantly changed by copper ion + stress. The results showed that in the low concentration Cu2+ treatment could induce the three kinds of enzymes, in the high concentration Cu2+ treatment group, SOD and CAT and GPx on the inhibition of the effect. The sensitivity of the three antioxidant enzymes to copper ion showed a certain difference. The sensitivity of the three kinds of tissue enzymes to Cu2+ treatment was digestive gland> fascia> gill. The experimental results show that the single factor for copper in water pollutants, the C. gigas digestive gland tissue SOD, GPX and CAT activity has certain significance to it, but will it as index applied to the actual water need further study.

Pleural effusion levels of DJ-1 are increased in elderly lung cancer patients with malignant pleural effusions.

PubMed

Vavougios, George; Kerenidi, Theodora; Tsilioni, Irene; Zarogiannis, Sotirios G; Gourgoulianis, Konstantinos I

2015-01-01

DJ-1 is a multifunctional protein implicated in redox dependent cell fate decisions. The aim of our study was to determine the pleural fluid (PF) levels of DJ-1 in malignant pleural effusions (MPEs) secondary to lung cancer. Additionally, we opted to assess potential correlations of DJ-1 PF levels with the PF levels of superoxide dismutase-1 (SOD1) and 8-isoprostane that are known antioxidant enzymes and have been previously reported in MPEs. Forty lung cancer patients with cytological proof of MPE were enrolled in this study. The PF levels of DJ-1, SOD1, and 8-isoprostane were measured by means of enzyme-linked immunosorbent assay. The median PF levels of DJ-1 were 826 ng/mL (interquartile range, IQR: 482-1010 ng/mL). DJ-1 PF levels significantly correlated with PF Cu/Zn-SOD1 and PF 8-isoprostane levels (Spearman's rho, r; r = -0.476, P = 0.002 and r = -0.264, P = 0.033, respectively), PF lactate dehydrogenase (r = -0.497, P = 0.001) and total PF cell counts (r = -0.325, P = 0.041). Finally, in patients aged over 65 the PF DJ-1 levels were significantly higher than patients aged less than 65 (875 ng/mL vs. 607 ng/mL, respectively, P = 0.037). To our knowledge, this is the first report to determine DJ-1's levels in MPEs due to lung cancer. The negative correlations between DJ-1, SOD1, and 8-isorpostane warrant further investigation regarding the altered redox regulation associated with MPEs.

Adsorption of multi-heavy metals Zn and Cu onto surficial sediments: modeling and adsorption capacity analysis.

PubMed

Li, Shanshan; Zhang, Chen; Wang, Meng; Li, Yu

2014-01-01

Improved multiple regression adsorption models (IMRAMs) was developed to estimate the adsorption capacity of the components [Fe oxides (Fe), Mn oxides (Mn), organic materials (OMs), residuals] in surficial sediments for multi-heavy metal Zn and Cu. IMRAM is an improved version over MRAM, which introduces a computer program in the model developing process. As MRAM, Zn(Cu) IMRAM, and Cu(Zn) IMRAM again confirmed that there is significant interaction effects that control the adsorption of compounded Zn and Cu, which was neglected by additional adsorption model. The verification experiment shows that the relative deviation of the IMRAMs is less than 13%. It is revealed by the IMRAMs that Mn, which has the greatest adsorption capability for compounded Zn and Cu (54.889 and 161.180 mg/l, respectively), follows by interference adsorption capacity of Fe/Mn (-1.072 and -24.591 mg/l respectively). Zn and Cu influence each other through different mechanisms. When Zn is the adsorbate, compounded Cu mainly affects the adsorption capacities of Fe/Mn and Fe/Mn/OMs; while when Cu is the adsorbate, compounded Zn mainly exerts its effect on Mn, Fe/Mn, and Mn/OMs. It also shows that the compounded Zn or Cu weakened the interference adsorption of Fe/Mn, and meanwhile, strengthened the interference adsorption of Mn/OMs.

Investigation of the 66Zn(p,2pn) 64Cu and 68Zn(p,x) 64Cu nuclear processes up to 100 MeV: Production of 64Cu

NASA Astrophysics Data System (ADS)

Szelecsényi, F.; Steyn, G. F.; Kovács, Z.; Vermeulen, C.; van der Meulen, N. P.; Dolley, S. G.; van der Walt, T. N.; Suzuki, K.; Mukai, K.

2005-11-01

Cross-sections of the 66Zn(p,2pn)64Cu and 68Zn(p,x)64Cu nuclear processes were measured on highly enriched zinc targets using the stacked-foil activation technique up to 100 MeV. The new cross-sections were compared to literature data. The optimum energy range for production of 64Cu was found to be 70 → 35 MeV on 66Zn and 37 → 20 MeV on 68Zn. The thick-target yields were determined as 777 MBq/μAh (21.0 mCi/μAh) and 185 MBq/μAh (5.0 mCi/μAh), respectively. The yields of the longer-lived contaminant copper radioisotopes (i.e. 61Cu when using 66Zn as target material and both 61Cu and 67Cu in the case of 68Zn target material) were also calculated. The results obtained from the present study indicate that both reactions are suited for the production of 64Cu at a medium energy cyclotron. The optimum energy ranges are also complementary therefore the potential to utilize tandem targetry exists.

Facile synthesis of core-shell Cu2O@ ZnO structure with enhanced photocatalytic H2 production

NASA Astrophysics Data System (ADS)

Zhang, Yong-Hui; Jiu, Bei-Bei; Gong, Fei-Long; Lu, Kuan; Jiang, Nan; Zhang, Hao-Li; Chen, Jun-Li

2018-05-01

Core-shell Cu2O@ZnO composites were synthesized successfully based on a one-pot hydrothermal method in the presence of dioctyl sulfosuccinate sodium salt (AOT) surfactant. The Cu2O can be converted to rough core-shell Cu2O@ZnO structure by adjusting the amount of zinc powder added. The as-synthesized Cu2O@ZnO composites exhibited excellent photocatalytic activity and the amount of H2 generated using these composites was 4.5-fold more than that produced with Cu2O cubes. A possible photocatalytic mechanism for the Cu2O@ZnO composites with enhanced photocatalytic activity could be the separation by ZnO of the effective charge carriers.

[Oxidative stress in platelets at an oncopathology].

PubMed

Gorozhanskaya, E G; Sviridova, S P; Baykova, V N; Zubrikhina, G N; Dobrovolskaya, M M; Sitov, A V

2015-01-01

To determine the biochemical disorders in the blood coagulation mechanism associated with oxidative stress parameters of the antioxidant status were examined in platelets of 57 colorectal cancer patients, (including 21 patients before and after surgery), and 40 healthy individuals. We determined the total content of nitric oxide (NOx), levels of superoxide dismutase (Cu/ZnSOD), glutathione and malondialdehyde (MDA). Before treatment, we observed the changes in the antioxidant defense system of platelets, which did not depend on the prevalence of malignancy: elevated levels of SOD by 16% (p<0.05), reduced glutathione and MDA in 5.2 and 1.7 times, respectively. NOx levels did not differ from the norm. Significant shifts were found in the postoperative period: they consisted of the increase in the generation of NOx both on the third, and on the 10-th day after surgery. These changes reflect apparently platelet response to the inflammatory process associated with the surgical trauma and confirm the role of NOx as a mediator of inflammation. The content of SOD after surgery was significantly reduced, but return to a baseline on the 10-th day. Despite the significant increase in the number of platelets, no correlations of the studied parameters and their aggregation ability were found.The findings suggest that metabolic disorders in vascular-platelet hemostasis are associated with oxidative stress, which provides a basis for further study of the relationship of cancer to thrombosis.

Exogenous calcium induces tolerance to atrazine stress in Pennisetum seedlings and promotes photosynthetic activity, antioxidant enzymes and psbA gene transcripts.

PubMed

Erinle, Kehinde Olajide; Jiang, Zhao; Ma, Bingbing; Li, Jinmei; Chen, Yukun; Ur-Rehman, Khalil; Shahla, Andleeb; Zhang, Ying

2016-10-01

Calcium (Ca) has been reported to lessen oxidative damages in plants by upregulating the activities of antioxidant enzymes. However, atrazine mediated reactive oxygen species (ROS) reduction by Ca is limited. This study therefore investigated the effect of exogenously applied Ca on ROS, antioxidants activity and gene transcripts, the D1 protein (psbA gene), and chlorophyll contents in Pennisetum seedlings pre-treated with atrazine. Atrazine toxicity increased ROS production and enzyme activities (ascorbate peroxidase APX, peroxidase POD, Superoxide dismutase SOD, glutathione-S-transferase GST); but decreased antioxidants (APX, POD, and Cu/Zn SOD) and psbA gene transcripts. Atrazine also decreased the chlorophyll contents, but increased chlorophyll (a/b) ratio. Contrarily, Ca application to atrazine pre-treated seedlings lowered the harmful effects of atrazine by reducing ROS levels, but enhancing the accumulation of total chlorophyll contents. Ca-protected seedlings in the presence of atrazine manifested reduced APX and POD activity, whereas SOD and GST activity was further increased with Ca application. Antioxidant gene transcripts that were down-regulated by atrazine toxicity were up-regulated with the application of Ca. Calcium application also resulted in up-regulation of the D1 protein. In conclusion, ability of calcium to reverse atrazine-induced oxidative damage and calcium regulatory role on GST in Pennisetum was presented. Copyright © 2016 Elsevier Inc. All rights reserved.

Reactive oxygen species dynamics in roots of salt sensitive and salt tolerant cultivars of rice.

PubMed

Saini, Shivani; Kaur, Navdeep; Pati, Pratap Kumar

2018-06-01

Salinity stress is one of the major constraints for growth and survival of plants that affects rice productivity worldwide. Hence, in the present study, roots of two contrasting salinity sensitive cultivars, IR64 (IR64, salt sensitive) and Luna Suvarna (LS, salt tolerant) were compared with regard to the levels of reactive oxygen species (ROS) to derive clues for their differential salt stress adaptation mechanisms. In our investigation, the tolerant cultivar exhibited longer primary roots, more lateral roots, higher root number leading to increased root biomass, with respect to IR64. It was observed that LS roots maintained higher level of H 2 O 2 in comparison to IR64. The activities of various enzymes involved in enzymatic antioxidant defense mechanism (SOD, CAT, GPX, DHAR and MDHAR) were found to be greater in LS roots. Further, the higher transcript level accumulation of genes encoding ROS generating (RbohA, RbohD and RbohE) and scavenging enzymes (Fe-SOD, Chloroplastic Cu/Zn-SOD, CAT and DHAR) were noticed in the roots of tolerant cultivar, LS. Moreover, the content of other stress markers such as total protein and proline were also elevated in LS roots. While, the expression of proline biosynthesis gene (P5CS) and proline catabolism gene (PDH) was observed to be lower in LS. Copyright © 2018. Published by Elsevier Inc.

Superoxide Triggers an Acid Burst in Saccharomyces cerevisiae to Condition the Environment of Glucose-starved Cells*

PubMed Central

Baron, J. Allen; Laws, Kaitlin M.; Chen, Janice S.; Culotta, Valeria C.

2013-01-01

Although yeast cells grown in abundant glucose tend to acidify their extracellular environment, they raise the pH of the environment when starved for glucose or when grown strictly with non-fermentable carbon sources. Following prolonged periods in this alkaline phase, Saccharomyces cerevisiae cells will switch to producing acid. The mechanisms and rationale for this “acid burst” were unknown. Herein we provide strong evidence for the role of mitochondrial superoxide in initiating the acid burst. Yeast mutants lacking the mitochondrial matrix superoxide dismutase (SOD2) enzyme, but not the cytosolic Cu,Zn-SOD1 enzyme, exhibited marked acceleration in production of acid on non-fermentable carbon sources. Acid production is also dramatically enhanced by the superoxide-producing agent, paraquat. Conversely, the acid burst is eliminated by boosting cellular levels of Mn-antioxidant mimics of SOD. We demonstrate that the acid burst is dependent on the mitochondrial aldehyde dehydrogenase Ald4p. Our data are consistent with a model in which mitochondrial superoxide damage to Fe-S enzymes in the tricarboxylic acid (TCA) cycle leads to acetate buildup by Ald4p. The resultant expulsion of acetate into the extracellular environment can provide a new carbon source to glucose-starved cells and enhance growth of yeast. By triggering production of organic acids, mitochondrial superoxide has the potential to promote cell population growth under nutrient depravation stress. PMID:23281478

Simultaneous adsorption and degradation of Zn(2+) and Cu (2+) from wastewaters using nanoscale zero-valent iron impregnated with clays.

PubMed

Shi, Li-Na; Zhou, Yan; Chen, Zuliang; Megharaj, Mallavarapu; Naidu, Ravi

2013-06-01

Clays such as kaolin, bentonite and zeolite were evaluated as support material for nanoscale zero-valent iron (nZVI) to simultaneously remove Cu(2+) and Zn(2+) from aqueous solution. Of the three supported nZVIs, bentonite-supported nZVI (B-nZVI) was most effective in the simultaneous removal of Cu(2+) and Zn(2+) from a aqueous solution containing a 100 mg/l of Cu(2+) and Zn(2+), where 92.9 % Cu(2+) and 58.3 % Zn(2+) were removed. Scanning electronic microscope (SEM) revealed that the aggregation of nZVI decreased as the proportion of bentonite increased due to the good dispersion of nZVI, while energy dispersive spectroscopy (EDS) demonstrated the deposition of copper and zinc on B-nZVI after B-nZVI reacted with Cu(2+) and Zn(2+). A kinetics study indicated that removing Cu(2+) and Zn(2+) with B-nZVI accorded with the pseudo first-order model. These suggest that simultaneous adsorption of Cu(2+)and Zn(2+) on bentonite and the degradation of Cu(2+)and Zn(2+) by nZVI on the bentonite. However, Cu(2+) removal by B-nZVI was reduced rather than adsorption, while Zn(2+) removal was main adsorption. Finally, Cu(2+), Zn(2+), Ni(2+), Pb(2+) and total Cr from various wastewaters were removed by B-nZVI, and reusability of B-nZVI with different treatment was tested, which demonstrates that B-nZVI is a potential material for the removal of heavy metals from wastewaters.

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

PubMed Central

Wisniewska, Monika; Cremer, Malte; Wiehe, Lennart; Becker, Niels-Peter; Rijntjes, Eddy; Martitz, Janine; Renko, Kostja; Bührer, Christoph; Schomburg, Lutz

2017-01-01

Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n = 21) and control (n = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1–679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections. PMID:28358335

Toxicity of CuO nanoparticles to yeast Saccharomyces cerevisiae BY4741 wild-type and its nine isogenic single-gene deletion mutants.

PubMed

Kasemets, Kaja; Suppi, Sandra; Künnis-Beres, Kai; Kahru, Anne

2013-03-18

A suite of eight tentatively oxidative stress response-deficient Saccharomyces cerevisiae BY4741 single-gene mutants (sod1Δ, sod2Δ, yap1Δ, cta1Δ, ctt1Δ, gsh1Δ, glr1Δ, and ccs1Δ) and one copper-vulnerable mutant (cup2Δ) was used to elucidate weather the toxicity of CuO nanoparticles to S. cerevisiae is mediated by oxidative stress (OS). Specifically, sensitivity profiles of mutants' phenotypes and wild-type (wt) upon exposure to nano-CuO were compared. As controls, CuSO4 (solubility), bulk-CuO (size), H2O2, and menadione (OS) were used. Growth inhibition of wt and mutant strains was studied in rich YPD medium and cell viability in deionized water (DI). Dissolved Cu-ions were quantified by recombinant metal-sensing bacteria and chemical analysis. To wt strain nano-CuO was 32-fold more toxic than bulk-CuO: 24-h IC50 4.8 and 155 mg/L in DI and 643 and >20000 mg/L in YPD, respectively. In toxicant-free YPD medium, all mutants had practically similar growth patterns as wt. However, the mutant strains sod1Δ, sod2Δ, ccs1Δ, and yap1Δ showed up to 12-fold elevated sensitivity toward OS standard chemicals menadione and H2O2 but not to nano-CuO, indicating that CuO nanoparticles exerted toxicity to yeast cells via different mechanisms. The most vulnerable strain to all studied Cu compounds was the copper stress response-deficient strain cup2Δ (∼16-fold difference with wt), indicating that the toxic effect of CuO (nano)particles proceeds via dissolved Cu-ions. The dissolved copper solely explained the toxicity of nano-CuO in DI but not in YPD. Assumingly, in YPD nano-CuO acquired a coating of peptides/proteins and sorbed onto the yeast's outer surface, resulting in their increased solubility in the close vicinity of yeast cells and increased uptake of Cu-ions that was not registered by the assays used for the analysis of dissolved Cu-ions in the test medium. Lastly, as yeast retained its viability in DI even by 24th hour of incubation, the profiling of the acute basal toxicity of chemicals toward yeasts may be conducted in DI.

Simultaneous increase in strength and ductility by decreasing interface energy between Zn and Al phases in cast Al-Zn-Cu alloy.

PubMed

Han, Seung Zeon; Choi, Eun-Ae; Park, Hyun Woong; Lim, Sung Hwan; Lee, Jehyun; Ahn, Jee Hyuk; Hwang, Nong-Moon; Kim, Kwangho

2017-09-22

Cast-Al alloys that include a high amount of the second element in their matrix have comparatively high strength but low ductility because of the high volume fraction of strengthening phases or undesirable inclusions. Al-Zn alloys that have more than 30 wt% Zn have a tensile strength below 300 MPa, with elongation under 5% in the as-cast state. However, we found that after substitution of 2% Zn by Cu, the tensile strength of as-cast Al-Zn-Cu alloys was 25% higher and ductility was four times higher than for the corresponding Al-35% Zn alloy. Additionally, for the Al-43% Zn alloy with 2% Cu after 1 h solution treatment at 400 °C and water quenching, the tensile strength unexpectedly reached values close to 600 MPa. For the Al-33% Zn alloy with 2% Cu, the tensile strength was 500 MPa with 8% ductility. The unusual trends of the mechanical properties of Al-Zn alloys with Cu addition observed during processing from casting to the subsequent solution treatment were attributed to the precipitation of Zn in the Al matrix. The interface energy between the Zn particles and the Al matrix decreased when using a solution of Cu in Zn.

Protein charge ladders reveal that the net charge of ALS-linked superoxide dismutase can be different in sign and magnitude from predicted values

PubMed Central

Shi, Yunhua; Abdolvahabi, Alireza; Shaw, Bryan F

2014-01-01

This article utilized “protein charge ladders”—chemical derivatives of proteins with similar structure, but systematically altered net charge—to quantify how missense mutations that cause amyotrophic lateral sclerosis (ALS) affect the net negative charge (Z) of superoxide dismutase-1 (SOD1) as a function of subcellular pH and Zn2+ stoichiometry. Capillary electrophoresis revealed that the net charge of ALS-variant SOD1 can be different in sign and in magnitude—by up to 7.4 units per dimer at lysosomal pH—than values predicted from standard pKa values of amino acids and formal oxidation states of metal ions. At pH 7.4, the G85R, D90A, and G93R substitutions diminished the net negative charge of dimeric SOD1 by up to +2.29 units more than predicted; E100K lowered net charge by less than predicted. The binding of a single Zn2+ to mutant SOD1 lowered its net charge by an additional +2.33 ± 0.01 to +3.18 ± 0.02 units, however, each protein regulated net charge when binding a second, third, or fourth Zn2+ (ΔZ < 0.44 ± 0.07 per additional Zn2+). Both metalated and apo-SOD1 regulated net charge across subcellular pH, without inverting from negative to positive at the theoretical pI. Differential scanning calorimetry, hydrogen-deuterium exchange, and inductively coupled plasma mass spectrometry confirmed that the structure, stability, and metal content of mutant proteins were not significantly affected by lysine acetylation. Measured values of net charge should be used when correlating the biophysical properties of a specific ALS-variant SOD1 protein with its observed aggregation propensity or clinical phenotype. PMID:25052939

Colloidal synthesis of Cu-ZnO and Cu@CuNi-ZnO hybrid nanocrystals with controlled morphologies and multifunctional properties.

PubMed

Zeng, Deqian; Gong, Pingyun; Chen, Yuanzhi; Zhang, Qinfu; Xie, Qingshui; Peng, Dong-Liang

2016-06-02

Metal-semiconductor hybrid nanocrystals have received extensive attention owing to their multiple functionalities which can find wide technological applications. The utilization of low-cost non-noble metals to construct novel metal-semiconductor hybrid nanocrystals is important and meaningful for their large-scale applications. In this study, a facile solution approach is developed for the synthesis of Cu-ZnO hybrid nanocrystals with well-controlled morphologies, including nanomultipods, core-shell nanoparticles, nanopyramids and core-shell nanowires. In the synthetic strategy, Cu nanocrystals formed in situ serve as seeds for the heterogeneous nucleation and growth of ZnO, and it eventually forms various Cu-ZnO hetero-nanostructures under different reaction conditions. These hybrid nanocrystals possess well-defined and stable heterostructure junctions. The ultraviolet-visible-near infrared spectra reveal morphology-dependent surface plasmon resonance absorption of Cu and the band gap absorption of ZnO. Furthermore, we construct a novel Cu@CuNi-ZnO ternary hetero-nanostructure by incorporating the magnetic metal Ni into the pre-synthesized colloidal Cu nanocrystals. Such hybrid nanocrystals possess a magnetic Cu-Ni intermediate layer between the ZnO shell and the Cu core, and exhibit ferromagnetic/superparamagnetic properties which expand their functionalities. Finally, enhanced photocatalytic activities are observed in the as-prepared non-noble metal-ZnO hybrid nanocrystals. This study not only provides an economical way to prepare high-quality morphology-controlled Cu-ZnO hybrid nanocrystals for potential applications in the fields of photocatalysis and photovoltaic devices, but also opens up new opportunities in designing ternary non-noble metal-semiconductor hybrid nanocrystals with multifunctionalities.

Optical and electrical properties of copper-incorporated ZnS films applicable as solar cell absorbers

NASA Astrophysics Data System (ADS)

Mehrabian, M.; Esteki, Z.; Shokrvash, H.; Kavei, G.

2016-10-01

Un-doped and Cu-doped ZnS (ZnS:Cu) thin films were synthesized by Successive Ion Layer Absorption and Reaction (SILAR) method. The UV-visible absorption studies have been used to calculate the band gap values of the fabricated ZnS:Cu thin films. It was observed that by increasing the concentration of Cu2+ ions, the Fermi level moves toward the edge of the valence band of ZnS. Photoluminescence spectra of un-doped and Cu-doped ZnS thin films was recorded under 355 nm. The emission spectrum of samples has a blue emission band at 436 nm. The peak positions of the luminescence showed a red shift as the Cu2+ ion concentration was increased, which indicates that the acceptor level (of Cu2+) is getting close to the valence band of ZnS.

ZnO/Cu(InGa)Se.sub.2 solar cells prepared by vapor phase Zn doping

DOEpatents

Ramanathan, Kannan; Hasoon, Falah S.; Asher, Sarah E.; Dolan, James; Keane, James C.

2007-02-20

A process for making a thin film ZnO/Cu(InGa)Se.sub.2 solar cell without depositing a buffer layer and by Zn doping from a vapor phase, comprising: depositing Cu(InGa)Se.sub.2 layer on a metal back contact deposited on a glass substrate; heating the Cu(InGa)Se.sub.2 layer on the metal back contact on the glass substrate to a temperature range between about 100.degree. C. to about 250.degree. C.; subjecting the heated layer of Cu(InGa)Se.sub.2 to an evaporant species from a Zn compound; and sputter depositing ZnO on the Zn compound evaporant species treated layer of Cu(InGa)Se.sub.2.

Room-temperature wide-range luminescence and structural, optical, and electrical properties of SILAR deposited Cu-Zn-S nano-structured thin films

NASA Astrophysics Data System (ADS)

Jose, Edwin; Kumar, M. C. Santhosh

2016-09-01

We report the deposition of nanostructured Cu-Zn-S composite thin films by Successive Ionic Layer Adsorption and Reaction (SILAR) method on glass substrates at room temperature. The structural, morphological, optical, photoluminescence and electrical properties of Cu-Zn-S thin films are investigated. The results of X-ray diffraction (XRD) and Raman spectroscopy studies indicate that the films exhibit a ternary Cu-Zn-S structure rather than the Cu xS and ZnS binary composite. Scanning electron microscope (SEM) studies show that the Cu-Zn-S films are covered well over glass substrates. The optical band gap energies of the Cu-Zn-S films are calculated using UV-visible absorption measurements, which are found in the range of 2.2 to 2.32 eV. The room temperature photoluminescence studies show a wide range of emissions from 410 nm to 565 nm. These emissions are mainly due to defects and vacancies in the composite system. The electrical studies using Hall effect measurements show that the Cu-Zn-S films are having p-type conductivity.

Microstructure and properties of Cu-Sn-Zn-TiO 2 nano-composite coatings on mild steel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Weidong; Cao, Di; Jin, Yunxue

Cu-Sn-Zn coatings have been widely used in industry for their unique properties, such as good conductivity, high corrosion resistance and excellent solderability. To further improve the mechanical performance of Cu-Sn-Zn coatings, powder-enhanced method was applied and Cu-Sn-Zn-TiO 2 nano-composite coatings with different TiO 2 concentration were fabricated. The microstructure of Cu-Sn-Zn-TiO 2 nano-composite coatings were investigated by X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). The mechanical properties of coatings including microhardness and wear resistance were studied. The results indicate that the incorporation of TiO 2 nanoparticle can significantly influence the properties of Cu-Sn-Zn coatings. The microhardness of Cu-Sn-Zn coatingmore » was increased to 383 HV from 330 HV with 1 g/L TiO 2 addition. Also, the corrosion resistance of coating was enhanced. The effects of TiO 2 nanoparticle concentration on the microstructure, mechanical properties and corrosion resistance of Cu-Sn-Zn-TiO 2 nano-composite coatings were discussed.« less

Microstructure and properties of Cu-Sn-Zn-TiO 2 nano-composite coatings on mild steel

DOE PAGES

Gao, Weidong; Cao, Di; Jin, Yunxue; ...

2018-04-18

Cu-Sn-Zn coatings have been widely used in industry for their unique properties, such as good conductivity, high corrosion resistance and excellent solderability. To further improve the mechanical performance of Cu-Sn-Zn coatings, powder-enhanced method was applied and Cu-Sn-Zn-TiO 2 nano-composite coatings with different TiO 2 concentration were fabricated. The microstructure of Cu-Sn-Zn-TiO 2 nano-composite coatings were investigated by X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). The mechanical properties of coatings including microhardness and wear resistance were studied. The results indicate that the incorporation of TiO 2 nanoparticle can significantly influence the properties of Cu-Sn-Zn coatings. The microhardness of Cu-Sn-Zn coatingmore » was increased to 383 HV from 330 HV with 1 g/L TiO 2 addition. Also, the corrosion resistance of coating was enhanced. The effects of TiO 2 nanoparticle concentration on the microstructure, mechanical properties and corrosion resistance of Cu-Sn-Zn-TiO 2 nano-composite coatings were discussed.« less

Synthesis and characterization of Cu-Zn/TiO2 for the photocatalytic conversion of CO2 to methane.

PubMed

Rana, Adeem Ghaffar; Ahmad, Waqar; Al-Matar, Ali; Shawabkeh, Reyad; Aslam, Zaheer

2017-05-01

Different Cu-Zn/TiO 2 catalysts were synthesized by using the wet impregnation method. The prepared catalysts were used for the conversion of CO 2 into methane by photocatalysis. Various characterization techniques were used to observe the surface morphology, crystalline phase, Brunauer-Emmett-Teller (BET) surface area, presence of impregnated Cu and Zn, and functional group. Scanning electron microscope analysis showed spherical morphology, and slight agglomeration of catalyst particles was observed. BET analysis revealed that the surface area of the catalyst was decreased from 10 to 8.5 m 2 /g after impregnation of Cu and Zn over TiO 2 support. Synergetic effect of Cu and Zn over TiO 2 support (Cu 2.6 /TiO 2 , Zn 0.5 /TiO 2 and Cu 2.6 -Zn 0.5 /TiO 2 ) and the effects of Cu loading (0, 1.8, 2.1, 2.6 and 2.9 wt%) were also investigated at different feed molar ratios of H 2 /CO 2 (2:1 and 4:1). The Cu 2.6 -Zn 0.5 /TiO 2 catalyst showed a maximum conversion of 14.3% at a feed molar ratio of 4. The addition of Zn over the catalyst surface increased the conversion of CO 2 from 10% to 14.3% which might be due to synergy of Cu and Zn over TiO 2 support.

Trace amounts of Cu²⁺ ions influence ROS production and cytotoxicity of ZnO quantum dots.

PubMed

Moussa, Hatem; Merlin, Christophe; Dezanet, Clément; Balan, Lavinia; Medjahdi, Ghouti; Ben-Attia, Mossadok; Schneider, Raphaël

2016-03-05

3-Aminopropyltrimethoxysilane (APTMS) was used as ligand to prepare ZnO@APTMS, Cu(2+)-doped ZnO (ZnO:Cu@APTMS) and ZnO quantum dots (QDs) with chemisorbed Cu(2+) ions at their surface (ZnO@APTMS/Cu). The dots have a diameter of ca. 5 nm and their crystalline and phase purities and composition were established by X-ray diffraction, transmission electron microscopy, UV-visible and fluorescence spectroscopies and by X-ray photoelectron spectroscopy. The effect of Cu(2+) location on the ability of the QDs to generate reactive oxygen species (ROS) under light irradiation was investigated. Results obtained demonstrate that all dots are able to produce ROS (OH, O2(-), H2O2 and (1)O2) and that ZnO@APTMS/Cu QDs generate more OH and O2(-) radicals and H2O2 than ZnO@APTMS and ZnO:Cu@APTMS QDs probably via mechanisms associating photo-induced charge carriers and Fenton reactions. In cytotoxicity experiments conducted in the dark or under light exposure, ZnO@APTMS/Cu QDs appeared slightly more deleterious to Escherichia coli cells than the two other QDs, therefore pointing out the importance of the presence of Cu(2+) ions at the periphery of the nanocrystals. On the other hand, with the lack of photo-induced toxicity, it can be inferred that ROS production cannot explain the cytotoxicity associated to the QDs. Our study demonstrates that both the production of ROS from ZnO QDs and their toxicity may be enhanced by chemisorbed Cu(2+) ions, which could be useful for medical or photocatalytic applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Thermochemistry of paddle wheel MOFs: Cu-HKUST-1 and Zn-HKUST-1.

PubMed

Bhunia, Manas K; Hughes, James T; Fettinger, James C; Navrotsky, Alexandra

2013-06-25

Metal-organic framework (MOF) porosity relies upon robust metal-organic bonds to retain structural rigidity upon solvent removal. Both the as-synthesized and activated Cu and Zn polymorphs of HKUST-1 were studied by room temperature acid solution calorimetry. Their enthalpies of formation from dense assemblages (metal oxide (ZnO or CuO), trimesic acid (TMA), and N,N-dimethylformamide (DMF)) were calculated from the calorimetric data. The enthalpy of formation (ΔHf) of the as-synthesized Cu-HKUST-H2O ([Cu3TMA2·3H2O]·5DMF) is -52.70 ± 0.34 kJ per mole of Cu. The ΔHf for Zn-HKUST-DMF ([Zn3TMA2·3DMF]·2DMF) is -54.22 ± 0.57 kJ per mole of Zn. The desolvated Cu-HKUST-dg [Cu3TMA2] has a ΔHf of 16.66 ± 0.51 kJ/mol per mole Cu. The ΔHf for Zn-HKUST-amorph [Zn3TMA2·2DMF] is -3.57 ± 0.21 kJ per mole of Zn. Solvent stabilizes the Cu-HKUST-H2O by -69.4 kJ per mole of Cu and Zn-HKUST-DMF by at least -50.7 kJ per mole of Zn. Such strong chemisorption of solvent is similar in magnitude to the strongly exothermic binding at low coverage for chemisorbed H2O on transition metal oxide nanoparticle surfaces. The strongly exothermic solvent-framework interaction suggests that solvent can play a critical role in obtaining a specific secondary building unit (SBU) topology.

The Cu2ZnSnSe4 thin films solar cells synthesized by electrodeposition route

NASA Astrophysics Data System (ADS)

Li, Ji; Ma, Tuteng; Wei, Ming; Liu, Weifeng; Jiang, Guoshun; Zhu, Changfei

2012-06-01

An electrodeposition route for preparing Cu2ZnSnSe4 thin films for thin film solar cell absorber layers is demonstrated. The Cu2ZnSnSe4 thin films are prepared by co-electrodeposition Cu-Zn-Sn metallic precursor and subsequently annealing in element selenium atmosphere. The structure, composition and optical properties of the films were investigated by X-ray diffraction (XRD), Raman spectrometry, energy dispersive spectrometry (EDS) and UV-VIS absorption spectroscopy. The Cu2ZnSnSe4 thin film with high crystalline quality was obtained, the band gap and absorption coefficient were 1.0 eV and 10-4 cm-1, which is quite suitable for solar cells fabrication. A solar cell with the structure of ZnO:Al/i-ZnO/CdS/Cu2ZnSnSe4/Mo/glass was fabricated and achieved an conversion efficiency of 1.7%.

Physiological and biochemical responses of Salix integra Thunb. under copper stress as affected by soil flooding.

PubMed

Cao, Yini; Ma, Chuanxin; Chen, Guangcai; Zhang, Jianfeng; Xing, Baoshan

2017-06-01

To explore the joint effect of copper (Cu) and flooding on Salix integra Thunb. (S. integra), the physiological and biochemical parameters of the seedlings grown in Cu amended soil (50, 150, 450 mg kg -1 ) with or without the flooding for 60 days were evaluated. The results suggested that the flooding significantly inhibited the root growth in terms of root length and root tips. The Cu exposures of 50 and 150 mg kg -1 notably enhanced the root growth as compared to the control. Majority of Cu was accumulated in S. integra roots, while flooding significantly reduced the Cu content, except the 150 mg kg -1 Cu treatment, but the iron (Fe) and manganese (Mn) content on the root surface were both markedly increased relative to non-flooded control. The malonaldehyde (MDA) and glutathione (GSH) contents in leaves showed a dose-response upon Cu exposure. Soil flooding enhanced the GSH level, which displayed 4.50-49.59% increases compared to its respective non-flooded treatment, while no difference was evident on MDA contents between the flooding and the non-flooded treatments. Both superoxide dismutase (SOD) and peroxidase (POD) activities were boosted while the catalase (CAT) was suppressed with increasing Cu exposure dose, and soil flooding reduced the POD and CAT activities. The elevated Cu level caused the evident increases of root calcium (Ca), potassium (K), and sulfur (S) concentrations and decreases of root phosphorus (P), sodium (Na), and zinc (Zn) concentrations. Soil flooding increased the concentrations of Fe, S, Na, Ca, and magnesium (Mg) in S. integra root. Taken together, our results suggested S. integra has high tolerance to the joint stress from Cu and flooding. Copyright © 2017 Elsevier Ltd. All rights reserved.

Defect evolution and its impact on the ferromagnetism of Cu-doped ZnO nanocrystals upon thermal treatment: A positron annihilation study

NASA Astrophysics Data System (ADS)

Chen, Zhi-Yuan; Chen, Yuqian; Zhang, Q. K.; Qi, N.; Chen, Z. Q.; Wang, S. J.; Li, P. H.; Mascher, P.

2017-01-01

CuO/ZnO nanocomposites with 4 at. % CuO were annealed in air at various temperatures between 100 and 1200 °C to produce Cu-doped ZnO nanocrystals. X-ray diffraction shows that a CuO phase can be observed in the CuO/ZnO nanocomposites annealed at different temperatures, and the Cu-doped ZnO nanocrystals are identified to be of wurtzite structure. The main peak (101) appears at slightly lower diffraction angles with increasing annealing temperature from 400 up to 1200 °C, which confirms the successful doping of Cu into the ZnO lattice above 400 °C. Scanning electron microscopy indicates that most particles in the CuO/ZnO nanocomposites are isolated when annealing at 100-400 °C, but these particles have a tendency to form clusters or aggregates as the annealing temperature increases from 700 to 1000 °C. Positron annihilation measurements reveal a large number of vacancy defects in the interface region of the nanocomposites, and they are gradually recovered with increasing annealing temperature up to 1000 °C. Room-temperature ferromagnetism can be observed in the CuO/ZnO nanocomposites, and the magnetization decreases continuously with increasing annealing temperature. However, there may be several different origins of ferromagnetism in the CuO/ZnO nanocomposites. At low annealing temperatures, the ferromagnetism originates from the CuO nanograins, and the ferromagnetism of CuO nanograins decreases with an increase in the grain size after subsequent higher temperature annealing, which leads to the weakening of ferromagnetism in the CuO/ZnO nanocomposites. After annealing from 400 to 1000 °C, the ferromagnetism gradually vanishes. The ferromagnetism is probably induced by Cu substitution but is mediated by vacancy defects in the CuO/ZnO nanocomposites. The disappearance of ferromagnetism coincides well with the recovery of vacancy defects. It can be inferred that the ferromagnetism is mediated by vacancy defects that are distributed in the interface region.

Cyclotron production of 61Cu using natural Zn & enriched 64Zn targets

NASA Astrophysics Data System (ADS)

Asad, A. H.; Smith, S. V.; Chan, S.; Jeffery, C. M.; Morandeau, L.; Price, R. I.

2012-12-01

Copper-61 (61Cu) shares with 64Cu certain advantages for PET diagnostic imaging, but has a shorter half-life (3.4hr vs. 12.7hr) and a greater probability of positron production per disintegration (61% vs. 17.9%). One important application is for in vivo imaging of hypoxic tissue. In this study 61Cu was produced using the 64Zn(p,α)61Cu reaction on natural Zn or enriched 64Zn targets. The enriched 64Zn (99.82%) was electroplated onto high purity gold or silver foils or onto thin Al discs. A typical target bombardment used 30μA; at 11.7, 14.5 or 17.6MeV over 30-60min. The 61Cu (radiochemical purity of >95%) was separated using a combination of cation and anion exchange columns. The 64Zn target material was recovered after each run, for re-use. In a direct comparison with enriched 64Zn-target results, 61Cu production using the cheaper natZn target proved to be an effective alternative.

Effects of Cu(2+) and Zn(2+) on growth and physiological characteristics of green algae, Cladophora.

PubMed

Cao, De-ju; Xie, Pan-pan; Deng, Juan-wei; Zhang, Hui-min; Ma, Ru-xiao; Liu, Cheng; Liu, Ren-jing; Liang, Yue-gan; Li, Hao; Shi, Xiao-dong

2015-11-01

Effects of various concentrations of Cu(2+) and Zn(2+) (0.0, 0.1, 0.25, 0.5, or 1.0 mg/L) on the growth, malondialdehyde (MDA), the intracellular calcium, and physiological characteristics of green algae, Cladophora, were investigated. Low Zn(2+) concentrations accelerated the growth of Cladophora, whereas Zn(2+) concentration increases to 0.25 mg/L inhibited its growth. Cu(2+) greatly influences Cladophora growth. The photosynthesis of Cladophora decreased under Zn(2+) and Cu(2+) stress. Cu(2+) and Zn(2+) treatment affected the content of total soluble sugar in Cladophora and has small increases in its protein content. Zn(2+) induced the intracellular calcium release, and copper induced the intracellular calcium increases in Cladophora. Exposure to Cu(2+) and Zn(2+) induces MDA in Cladophora. The stress concent of Cu(2+) was strictly correlated with the total soluble sugar content, Chla+Chlb, and MDA in Cladophora, and the stress concent of Zn(2+) was strictly correlated with the relative growth rate (RGR) and MDA of Cladophora.

Cu-Zn isotope constraints on the provenance of air pollution in Central Europe: Using soluble and insoluble particles in snow and rime.

PubMed

Novak, Martin; Sipkova, Adela; Chrastny, Vladislav; Stepanova, Marketa; Voldrichova, Petra; Veselovsky, Frantisek; Prechova, Eva; Blaha, Vladimir; Curik, Jan; Farkas, Juraj; Erbanova, Lucie; Bohdalkova, Leona; Pasava, Jan; Mikova, Jitka; Komarek, Arnost; Krachler, Michael

2016-11-01

Copper (Cu) and zinc (Zn) isotope ratios can be used to fingerprint sources and dispersion pathways of pollutants in the environment. Little is known, however, about the potential of δ 65 Cu and δ 66 Zn values in liquid and solid forms of atmospheric deposition to distinguish between geogenic, industrial, local and remote sources of these potentially toxic base metals. Here we present Cu-Zn deposition fluxes at 10 mountain-top sites in the Czech Republic, a region affected by extremely high industrial emission rates 25 years ago. Additionally, we monitored isotope composition of Cu and Zn in vertical and horizontal atmospheric deposition at two sites. We compared δ 65 Cu and δ 66 Zn values in snow and rime, extracted by diluted HNO 3 and concentrated HF. Cu and Zn isotope signatures of industrial pollution sources were also determined. Cu and Zn deposition fluxes at all study sites were minute. The mean δ 65 Cu value of atmospheric deposition (-0.07‰) was higher than the mean δ 65 Cu value of pollution sources (-1.17‰). The variability in δ 65 Cu values of atmospheric deposition was lower, compared to the pollution sources. The mean δ 66 Zn value of atmospheric deposition (-0.09‰) was slightly higher than the mean δ 66 Zn value of pollution sources (-0.23‰). The variability in δ 66 Zn values of atmospheric deposition was indistinguishable from that of pollution sources. The largest isotope differences (0.35‰) were observed between the insoluble and soluble fractions of atmospheric deposition. These differences may result from different sources of Cu/Zn for each fraction. The difference in isotope composition of soluble and insoluble particles appears to be a promising tool for pollution provenance studies in Central Europe. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in urinary Cu, Zn, and Se levels in cancer patients after treatment with Sha Shen Mai Men Dong Tang

PubMed Central

Lai, Tung-Yuan; Kuo, Hsien-Wen

2015-01-01

Sha Shen Mai Men Dong Tang (SMD-2; 沙參麥冬湯 shā shēn mài dōng tāng) is a Chinese medicinal herb (CMH; 中草藥 zhōng cǎo yào) used to treat symptoms associated with cancer therapy. The objective of this study was to assess the effect of SMD-2 on the levels of urinary copper (Cu), zinc (Zn), and selenium (Se) in lung cancer patients and head and neck cancer patients receiving chemoradiotherapy. Forty-two head and neck cancer patients and 10 lung cancer patients participated in our clinical trial. Each patient received chemoradiotherapy for 4 weeks. In addition, each patient was treated with SMD-2 for 8 weeks, including 2 weeks prior to and after the chemoradiotherapy treatment. Comparison of urinary Cu, Zn, and Se levels and the ratios of Zn to Cu and Se to Cu at three time points in the two types of cancer were assessed using the generalized estimating equations (GEEs). After the patients received chemoradiotherapy for 4 weeks, SMD-2 treatment was found to be associated with a significant decrease in urinary Cu levels, whereas urinary Zn and Se levels increased significantly. In addition, the ratios of Zn to Cu and Se to Cu in the urine samples of these patients also increased significantly. Both the urinary Zn levels and the ratio of Zn to Cu in head and neck cancer patients were significantly higher than in lung cancer patients. Urinary Zn and Se levels and the ratios of Zn to Cu and Se to Cu, but not urinary Cu levels, increased significantly during and after treatment when assessed using the GEE model. The SMD-2 treatments significantly increased Zn and Se levels in the urine of head and neck cancer patients. Increased Zn and Se levels in urine strengthened immune system. PMID:27114935

Luminescence, magnetic and vibrational properties of novel heterometallic niccolites [(CH3)2NH2][CrIIIMII(HCOO)6] (MII=Zn, Ni, Cu) and [(CH3)2NH2][AlIIIZnII(HCOO)6]:Cr3+

NASA Astrophysics Data System (ADS)

Mączka, Mirosław; Pietraszko, Adam; Pikul, Adam; Hermanowicz, Krzysztof

2016-01-01

We report synthesis of three novel heterometallic MOFs, [(CH3)2NH2][CrIIIMII(HCOO)6] with M=Zn (DMCrZn), Ni (DMCrNi) and Cu (DMCrCu), crystallizing in the niccolite type structure. We also successfully synthesized [(CH3)2NH2][AlCu(HCOO)6] (DMAlCu) and [(CH3)2NH2][AlZn(HCOO)6] doped with 5.8 mol% of Cr3+ (DMAlZn: Cr). X-ray diffraction shows that DMCrZn, DMCrNi and DMAlZn: Cr3+ crystallize in the trigonal structure (space group P 3 bar1c) while DMCrCu and DMAlCu crystallize in the monoclinic structure (space group C2/c). Magnetic investigation of the chromium-based niccolites reveals no magnetic order in DMCrZn and ferromagnetic order in DMCrNi and DMCrCu below 23 and 11 K, respectively. Optical studies show that DMCrZn and DMAlZn: Cr samples exhibit efficient emission typical for chromium ions located at sites of strong crystal field with the Dq/B values 2.62 and 2.67, respectively. We also discuss role of geometrical parameters in stability of the perovskite and niccolite structures.

First Measurement of the Radionuclide Purity of the Therapeutic Isotope 67Cu Produced by 68Zn(n,x) Reaction Using natC(d,n) Neutrons

NASA Astrophysics Data System (ADS)

Sato, Nozomi; Tsukada, Kazuaki; Watanabe, Satoshi; Ishioka, Noriko S.; Kawabata, Masako; Saeki, Hideya; Nagai, Yasuki; Kin, Tadahiro; Minato, Futoshi; Iwamoto, Nobuyuki; Iwamoto, Osamu

2014-07-01

We have for the first time studied the radionuclide purity of the therapeutic isotope 67Cu produced by the 68Zn(n,x)67Cu reaction. The neutrons were obtained by the natC(d,n) reaction using 40 MeV deuterons. We measured the γ-ray spectra of the reaction products produced by bombarding an enriched 68ZnO sample with the neutrons with a high-purity Ge detector. We found that the relative production yields of the impurity radionuclides 64Cu, 65Zn, and 69mZn to 67Cu are extremely low. The result indicates that the 68Zn(n,x)67Cu reaction is the most promising among those proposed routes until now for producing high-quality 67Cu, and could solve a longstanding problem of establishing an appropriate production method for 67Cu.

Visible light-driven photocatalytic H{sub 2}-generation activity of CuS/ZnS composite particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Liang; Chen, Hua; Huang, Jianhua, E-mail: jhhuang@zstu.edu.cn

2015-04-15

Highlights: • Preparation of CuS/ZnS composite photocatalyst by cation-exchange reaction. • Visible light photocatalytic activity for H{sub 2} evolution without cocatalyst. • The H{sub 2}-evolution rate from water splitting depends on the CuS content. • The highest rate of H{sub 2} evolution is obtained with CuS (0.5 mol%)/ZnS composite. - Abstract: CuS/ZnS composite particles with diameter of 200–400 nm were successfully prepared by a simple cation-exchange reaction using ZnS spheres as a precursor. CuS nanoparticles with a few nanometers in diameter were observed on the surface of composite particles. The synthesized CuS/ZnS composite particles showed photocatalytic property effective for H{submore » 2} evolution from an aqueous Na{sub 2}S and Na{sub 2}SO{sub 3} solution under visible light irradiation without any cocatalysts. The rate of H{sub 2} generation was found to be strongly dependent on the CuS content. The highest rate of H{sub 2} evolution reached 695.7 μmol h{sup −1} g{sup −1}, which was almost 7 times as high as that of the mechanical mixture of CuS and ZnS. The enhancement in the photocatalytic activity of CuS/ZnS composite particles is supposed to be due to the direct interfacial charge transfer of the CuS/ZnS heterojunction.« less

Replacement of buried cysteine from zebrafish Cu/Zn superoxide dismutase and enhancement of its stability via site-directed mutagenesis.

PubMed

Ken, Chuian-Fu; Lin, Chi-Tsai; Wen, Yu-Der; Wu, Jen-Leih

2007-01-01

Zebrafish Cu/Zn-superoxide dismutase (ZSOD1) has one free cysteine (Cys-7) in a first beta-strand with lower thermostability. We predicted the stability would be increased with single-point mutation at 70 degrees C via the I-Mutant 2.0 server, and generated a mutant SOD with replacement of the free Cys to Ala (ZSODC7A) by site-directed mutagenesis. The mutant was expressed and purified from the Escherichia coli strain AD494(DE3)pLysS and the yield was 2 mg from 0.4 L of culture. The ZSODC7A was heated at 90 degrees C. In a time-dependent assay, the time interval for 50% inactivation was 32 min, and its thermal inactivation rate constant K (d) was 2 x 10(-2) min(-1). The mutant was still activated in broad pH range (2.3-12), and had only a moderate effect under sodium dodecyl sulfate treatment. The calculated specific activity of the mutant was 3980 U/mg, twice that of wild-type ZSOD1. In addition, we soaked fish larva with equal enzyme units of either ZSOD1 or ZSODC7A for 2 h, and then stressed them with 100 ppm of paraquat to induce oxidative injury. The survival rate was significant.

Synthesis and photoelectrochemical properties of a novel CuO/ZnO nanorod photocathode for solar hydrogen generation

NASA Astrophysics Data System (ADS)

Shaislamov, Ulugbek; Lee, Heon-Ju

2016-10-01

Here, we present a facile synthesis method and photoelectrochemical characterizations of a p-type CuO-nanorod array photoelectrode with ZnO nanorod branches. Vertically-aligned CuO nanorods were synthesized by using direct oxidation of metallic Cu nanorods grown on a Cu substrate by using a facile template-assisted electrodeposition method. The formed CuONR/ZnONB hierarchically-structured photoelectrode exhibited remarkable photoelectrodechemical performance and outstanding stability compared to the CuO NR photoelectrode without ZnO NR branches. Morphological, optical and electrochemical characterizations were carried out in order to examine the effects of ZnO nanorod branches on the stability and the overall electrochemical performance of the electrode.

Dilute electrodeposition of TiO2 and ZnO thin film memristors on Cu substrate

NASA Astrophysics Data System (ADS)

Fauzi, F. B.; Ani, M. H.; Herman, S. H.; Mohamed, M. A.

2018-03-01

Memristor has become one of the alternatives to replace the current memory technologies. Fabrication of titanium dioxide, TiO2 memristor has been extensively studied by using various deposition methods. However, recently more researches have been done to explore the compatibility of other transition metal oxide, TMO such as zinc oxide, ZnO to be used as the active layer of the memristor. This paper highlights the simple and easy-control electrodeposition to deposit titanium, Ti and zinc, Zn thin film at room temperature and subsequent thermal oxidation at 600 °C. Gold, Au was then sputtered as top electrode to create metal-insulator-metal, MIM sandwich of Au/TiO2-Cu2O-CuO/Cu and Au/ZnO-Cu2O-CuO/Cu memristors. The structural, morphological and memristive properties were characterized using Field Emission Scanning Electron Microscopy, FESEM, X-Ray Diffraction, XRD and current-voltage, I-V measurement. Both Au/TiO2-Cu2O-CuO/Cu and Au/ZnO-Cu2O-CuO/Cu memristivity were identified by the pinched hysteresis loop with resistive ratio of 1.2 and 1.08 respectively. Empirical study on diffusivity of Ti4+, Zn2+ and O2‑ ions in both metal oxides show that the metal vacancies were formed, thus giving rise to its memristivity. The electrodeposited Au/TiO2-Cu2O-CuO/Cu and Au/ZnO-Cu2O-CuO/Cu memristors demonstrate comparable performances to previous studies using other methods.

CuO and ZnO nanoparticles: phytotoxicity, metal speciation, and induction of oxidative stress in sand-grown wheat

NASA Astrophysics Data System (ADS)

Dimkpa, Christian O.; McLean, Joan E.; Latta, Drew E.; Manangón, Eliana; Britt, David W.; Johnson, William P.; Boyanov, Maxim I.; Anderson, Anne J.

2012-09-01

Metal oxide nanoparticles (NPs) are reported to impact plant growth in hydroponic systems. This study describes the impact of commercial CuO (<50 nm) and ZnO (<100 nm) NPs on wheat ( Triticum aestivum) grown in a solid matrix, sand. The NPs contained both metallic and non-metallic impurities to different extents. Dynamic light scattering and atomic force microscopy (AFM) assessments confirmed aggregation of the NPs to submicron sizes. AFM showed transformation of ZnO NPs from initial rhomboid shapes in water to elongated rods in the aqueous phase of the sand matrix. Solubilization of metals occurred in the sand at similar rates from CuO or ZnO NPs as their bulk equivalents. Amendment of the sand with 500 mg Cu and Zn/kg sand from the NPs significantly ( p = 0.05) reduced root growth, but only CuO NPs impaired shoot growth; growth reductions were less with the bulk amendments. Dissolved Cu from CuO NPs contributed to their phytotoxicity but Zn release did not account for the changes in plant growth. Bioaccumulation of Cu, mainly as CuO and Cu(I)-sulfur complexes, and Zn as Zn-phosphate was detected in the shoots of NP-challenged plants. Total Cu and Zn levels in shoot were similar whether NP or bulk materials were used. Oxidative stress in the NP-treated plants was evidenced by increased lipid peroxidation and oxidized glutathione in roots and decreased chlorophyll content in shoots; higher peroxidase and catalase activities were present in roots. These findings correlate with the NPs causing increased production of reactive oxygen species. The accumulation of Cu and Zn from NPs into edible plants has relevance to the food chain.

Elastocaloric effect in CuAlZn and CuAlMn shape memory alloys under compression

PubMed Central

Qian, Suxin; Wang, Yi; Pillsbury, Thomas E.; Hada, Yoshiharu; Yamaguchi, Yuki; Fujimoto, Kenjiro; Hwang, Yunho; Radermacher, Reinhard; Cui, Jun; Yuki, Yoji; Toyotake, Koutaro; Takeuchi, Ichiro

2016-01-01

This paper reports the elastocaloric effect of two Cu-based shape memory alloys: Cu68Al16Zn16 (CuAlZn) and Cu73Al15Mn12 (CuAlMn), under compression at ambient temperature. The compression tests were conducted at two different rates to approach isothermal and adiabatic conditions. Upon unloading at a strain rate of 0.1 s−1 (adiabatic condition) from 4% strain, the highest adiabatic temperature changes (ΔTad) of 4.0 K for CuAlZn and 3.9 K for CuAlMn were obtained. The maximum stress and hysteresis at each strain were compared. The stress at the maximum recoverable strain of 4.0% for CuAlMn was 120 MPa, which is 70% smaller than that of CuAlZn. A smaller hysteresis for the CuAlMn alloy was also obtained, about 70% less compared with the CuAlZn alloy. The latent heat, determined by differential scanning calorimetry, was 4.3 J g−1 for the CuAlZn alloy and 5.0 J g−1 for the CuAlMn alloy. Potential coefficients of performance (COPmat) for these two alloys were calculated based on their physical properties of measured latent heat and hysteresis, and a COPmat of approximately 13.3 for CuAlMn was obtained. This article is part of the themed issue ‘Taking the temperature of phase transitions in cool materials’. PMID:27402936

Isotopic variations of dissolved copper and zinc in stream waters affected by historical mining

USGS Publications Warehouse

Borrok, D.M.; Nimick, D.A.; Wanty, R.B.; Ridley, W.I.

2008-01-01

Zinc and Cu play important roles in the biogeochemistry of natural systems, and it is likely that these interactions result in mass-dependent fractionations of their stable isotopes. In this study, we examine the relative abundances of dissolved Zn and Cu isotopes in a variety of stream waters draining six historical mining districts located in the United States and Europe. Our goals were to (1) determine whether streams from different geologic settings have unique or similar Zn and Cu isotopic signatures and (2) to determine whether Zn and Cu isotopic signatures change in response to changes in dissolved metal concentrations over well-defined diel (24-h) cycles. Average ??66Zn and ??65Cu values for streams varied from +0.02??? to +0.46??? and -0.7??? to +1.4???, respectively, demonstrating that Zn and Cu isotopes are heterogeneous among the measured streams. Zinc or Cu isotopic changes were not detected within the resolution of our measurements over diel cycles for most streams. However, diel changes in Zn isotopes were recorded in one stream where the fluctuations of dissolved Zn were the largest. We calculate an apparent separation factor of ???0.3??? (66/64Zn) between the dissolved and solid Zn reservoirs in this stream with the solid taking up the lighter Zn isotope. The preference of the lighter isotope in the solid reservoir may reflect metabolic uptake of Zn by microorganisms. Additional field investigations must evaluate the contributions of soils, rocks, minerals, and anthropogenic components to Cu and Zn isotopic fluxes in natural waters. Moreover, rigorous experimental work is necessary to quantify fractionation factors for the biogeochemical reactions that are likely to impact Cu and Zn isotopes in hydrologic systems. This initial investigation of Cu and Zn isotopes in stream waters suggests that these isotopes may be powerful tools for probing biogeochemical processes in surface waters on a variety of temporal and spatial scales.

Aided phytoextraction of Cu, Pb, Zn, and As in copper-contaminated soils with tobacco and sunflower in crop rotation: Mobility and phytoavailability assessment.

PubMed

Hattab-Hambli, Nour; Motelica-Heino, Mikael; Mench, Michel

2016-02-01

Copper-contaminated soils were managed with aided phytoextraction in 31 field plots at a former wood preservation site, using a single incorporation of compost (OM) and dolomitic limestone (DL) followed by a crop rotation with tobacco and sunflower. Six amended plots, with increasing total soil Cu, and one unamended plot were selected together with a control uncontaminated plot. The mobility and phytoavailability of Cu, Zn, Cr and As were investigated after 2 and 3 years in soil samples collected in these eight plots. Total Cu, Zn, Cr and As concentrations were determined in the soil pore water (SPW) and available soil Cu and Zn fractions by DGT. The Cu, Zn, Cr and As phytoavailability was characterized by growing dwarf beans on potted soils and determining the biomass of their plant parts and their foliar ionome. Total Cu concentrations in the SPW increased with total soil Cu. Total Cu, Zn, Cr and As concentrations in the SPW decreased in year 3 as compared to year 2, likely due to annual shoot removals by the plants and the lixiviation. Available soil Cu and Zn fractions also declined in year 3. The Cu, Zn, Cr and As phytoavailability, assessed by their concentration and mineral mass in the primary leaves of beans, was reduced in year 3. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation, structural, photoluminescence and magnetic studies of Cu doped ZnO nanoparticles co-doped with Ni by sol-gel method

NASA Astrophysics Data System (ADS)

Theyvaraju, D.; Muthukumaran, S.

2015-11-01

Zn0.96-xNi0.04CuxO nanoparticles have been synthesized by varying different Cu concentrations between 0% and 4% using simple sol-gel method. X-ray diffraction studies confirmed the hexagonal structure of the prepared samples. The formation of secondary phases, CuO (111) and Zn (101) at higher Cu content is due un-reacted Cu2+ and Zn2+ ions present in the solution which reduces the interaction between precursor ions and surfaces of ZnO. Well agglomerated and rod-like structure noticed at Cu=4% greatly de-generate and enhanced the particle size. The nominal elemental composition of Zn, Cu, Ni and O was confirmed by energy dispersive X-ray analysis. Even though energy gap was increased (blue-shift) from Cu=0-2% by quantum size effect, the s-d and p-d exchange interactions between the band electrons of ZnO and localized d electrons of Cu and Ni led to decrease (red-shift) the energy gap at Cu=4%. Presence of Zn-Ni-Cu-O bond was confirmed by Fourier transform infrared analysis. Ultraviolet emission by band to band electronic transition and defect related blue emission were discussed by photoluminescence spectra. The observed optical properties concluded that the doping of Cu in the present system is useful to tune the emission wavelength and hence acting as the important candidates for the optoelectronic device applications. Ferromagnetic ordering of Cu=2% sample was enhanced by charge carrier concentration where as the antiferromagnetic interaction between neighboring Cu-Cu ions suppressed the ferromagnetism at higher doping concentrations of Cu.

Theory of copper impurities in ZnO

NASA Astrophysics Data System (ADS)

Lyons, John; Alkauskas, Audrius; Janotti, Anderson; van de Walle, Chris G.

Due to its connection to deep luminescence signals and its potential use as an acceptor dopant, copper has been one the most studied impurities in ZnO. From experiment, copper incorporating on the Zn site (CuZn) is known to lead to an acceptor level residing near the conduction band of ZnO, making CuZn an exceedingly deep acceptor. CuZn in ZnO has also long been linked with broad 2.4 eV green luminescence (GL) signals. In this work we explore the electrical and optical properties of Cu in ZnO using density functional theory (DFT). Due to the limitations of traditional forms of DFT, an accurate theoretical description of the electrical and optical properties of such deep centers has been difficult to achieve. Here we employ a screened hybrid density functional (HSE) to calculate the properties of Cu in ZnO. We determine the thermodynamic transition levels associated with CuZn in ZnO as well as the associated luminescence lineshapes of characteristic optical transitions. We find that HSE-calculated optical transitions are in close agreement with experimental studies. This work was supported in part by NSF and by ARO.

The effect of Ti-B on stabilization of Cu-Zn-Al martensite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stipcich, M.; Romero, R.

1998-10-05

The application of shape memory effect in devices requires, in many cases, stable and reliable transformation temperatures. However, as a consequence of diffusional processes, in Cu-based shape memory alloys, reverse transformation temperature significantly rises after aging at temperatures above room temperature. This generally unwanted behavior is usually referred to as the stabilization of martensite. Numerous investigations have been carried out on this subject as reviewed by Ahlers and Chandrasekaran et al. Within the Cu-based alloys the Cu-Zn-Al are claimed to be more prone to stabilization than Cu-Al-Ni on aging. It has been proposed that in the Cu-Zn-Al the stabilization ismore » due to the interchange of Cu and Zn atoms assisted by vacancies, changing, consequently, the long range order inherited from the {beta} phase. In the present work, the authors investigate the stabilization behavior of polycrystalline samples of stress induced Cu-Zn-Al and Cu-Zn-Al-B martensite.« less

Copper status in weanling rats fed low levels of inorganic tin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rader, J.I.; Hight, S.C.

1991-03-15

The metabolism of Cu and Fe is adversely affected by ingestion of tin (Sn). In the present study, weanling male rats were fed 33 ug Sn/g in purified Cu-adequate or Cu-deficient diets for 14 or 28 days. Diets were based upon diet AIN-76A and contained 55% glucose and 15% starch. Ceruloplasmin was undetectable in serum of rats fed diets 2, 3 and 4 for 14 or 28 days. Superoxide dismutase (SOD) and Cu in liver decreased when 33 ug Sn/g was included in +Cu diets. Wt. gain, relative heart wt., SOD, and Cu and Fe in liver were sensitive indicesmore » of copper depletion in rats fed {minus}Cu diets. Cu status in rats fed {minus}Cu diets for 14 or 28 days was adversely affected by inclusion of Sn as indicated by changes in hemoglobin (HGB) and relative heart wt. Ingestion of low levels of inorganic tin causes Cu depletion in rats fed +Cu diets and accelerated the appearance of signs of copper deficiency in those fed {minus}Cu diets.« less

A Stable Plasmonic Cu@Cu2 O/ZnO Heterojunction for Enhanced Photocatalytic Hydrogen Generation.

PubMed

Lou, Yongbing; Zhang, Yake; Cheng, Lin; Chen, Jinxi; Zhao, Yixin

2018-05-09

The localized surface plasmon resonance (LSPR) effect has been widely utilized in photocatalysis, but most reported LSPR materials are based on noble metals of gold or silver with high chemical stability. Plasmonic copper nanoparticles that exhibit an LSPR absorbance at 600 nm are promising for many applications, such as photocatalysis. Unfortunately, plasmonic copper nanoparticles are affected by serious surface oxidation in air. Herein, a novel lollipop-shaped Cu@Cu 2 O/ZnO heterojunction nanostructure was designed, for the first time, to stabilize the plasmonic Cu core by decorating Cu@Cu 2 O core-shell structures with ZnO nanorods. This Cu@Cu 2 O/ZnO nanostructure exhibited significantly enhanced stability than that of regular Cu@Cu 2 O, which accounted for the remarkably enhanced photocatalytic H 2 evolution rate through water splitting, relative to pristine ZnO nanorods, over an extended wavelength range due to the plasmonic Cu core. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improved sensitivity of polychlorinated-biphenyl-orientated porous-ZnO surface photovoltage sensors from chemisorption-formed ZnO-CuPc composites

PubMed Central

Li, Mingtao; Meng, Guowen; Huang, Qing; Zhang, Shile

2014-01-01

We report a new mechanism for the enhancement of porous-ZnO surface photovoltage (SPV) response to polychlorinated biphenyls (PCBs, a notorious class of persistent organic pollutants as global environmental hazard) based on copper phthalocyanine (CuPc) chemisorptive bonding on porous-ZnO. A new ZnO-CuPc composite is formed on the porous-ZnO surface due to the interaction between the surface ZnO and CuPc, with its valence band (VB) energy level being higher than that of the pristine porous-ZnO. So that the efficiency of the photogenerated-electron transfer from the composite VB to the adjacent ZnO's surface states is drastically increased due to the reduced energy gap between the transition states. As a result, the sensitivity of the PCB-orientated SPV sensor is much improved by showing amplified variation of the SPV-signals perturbed by PCBs adsorbed on the ZnO-CuPc@porous-ZnO sensitive material. PMID:24594662

Protective Response Mechanisms to Heat Stress in Interaction with High [CO2] Conditions in Coffea spp.

PubMed Central

Martins, Madlles Q.; Rodrigues, Weverton P.; Fortunato, Ana S.; Leitão, António E.; Rodrigues, Ana P.; Pais, Isabel P.; Martins, Lima D.; Silva, Maria J.; Reboredo, Fernando H.; Partelli, Fábio L.; Campostrini, Eliemar; Tomaz, Marcelo A.; Scotti-Campos, Paula; Ribeiro-Barros, Ana I.; Lidon, Fernando J. C.; DaMatta, Fábio M.; Ramalho, José C.

2016-01-01

Modeling studies have predicted that coffee crop will be endangered by future global warming, but recent reports highlighted that high [CO2] can mitigate heat impacts on coffee. This work aimed at identifying heat protective mechanisms promoted by CO2 in Coffea arabica (cv. Icatu and IPR108) and Coffea canephora cv. Conilon CL153. Plants were grown at 25/20°C (day/night), under 380 or 700 μL CO2 L−1, and then gradually submitted to 31/25, 37/30, and 42/34°C. Relevant heat tolerance up to 37/30°C for both [CO2] and all coffee genotypes was observed, likely supported by the maintenance or increase of the pools of several protective molecules (neoxanthin, lutein, carotenes, α-tocopherol, HSP70, raffinose), activities of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), catalase (CAT), and the upregulated expression of some genes (ELIP, Chaperonin 20). However, at 42/34°C a tolerance threshold was reached, mostly in the 380-plants and Icatu. Adjustments in raffinose, lutein, β-carotene, α-tocopherol and HSP70 pools, and the upregulated expression of genes related to protective (ELIPS, HSP70, Chape 20, and 60) and antioxidant (CAT, CuSOD2, APX Cyt, APX Chl) proteins were largely driven by temperature. However, enhanced [CO2] maintained higher activities of GR (Icatu) and CAT (Icatu and IPR108), kept (or even increased) the Cu,Zn-SOD, APX, and CAT activities, and promoted a greater upregulation of those enzyme genes, as well as those related to HSP70, ELIPs, Chaperonins in CL153, and Icatu. These changes likely favored the maintenance of reactive oxygen species (ROS) at controlled levels and contributed to mitigate of photosystem II photoinhibition at the highest temperature. Overall, our results highlighted the important role of enhanced [CO2] on the coffee crop acclimation and sustainability under predicted future global warming scenarios. PMID:27446174

Protective Response Mechanisms to Heat Stress in Interaction with High [CO2] Conditions in Coffea spp.

PubMed

Martins, Madlles Q; Rodrigues, Weverton P; Fortunato, Ana S; Leitão, António E; Rodrigues, Ana P; Pais, Isabel P; Martins, Lima D; Silva, Maria J; Reboredo, Fernando H; Partelli, Fábio L; Campostrini, Eliemar; Tomaz, Marcelo A; Scotti-Campos, Paula; Ribeiro-Barros, Ana I; Lidon, Fernando J C; DaMatta, Fábio M; Ramalho, José C

2016-01-01

Modeling studies have predicted that coffee crop will be endangered by future global warming, but recent reports highlighted that high [CO2] can mitigate heat impacts on coffee. This work aimed at identifying heat protective mechanisms promoted by CO2 in Coffea arabica (cv. Icatu and IPR108) and Coffea canephora cv. Conilon CL153. Plants were grown at 25/20°C (day/night), under 380 or 700 μL CO2 L(-1), and then gradually submitted to 31/25, 37/30, and 42/34°C. Relevant heat tolerance up to 37/30°C for both [CO2] and all coffee genotypes was observed, likely supported by the maintenance or increase of the pools of several protective molecules (neoxanthin, lutein, carotenes, α-tocopherol, HSP70, raffinose), activities of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), catalase (CAT), and the upregulated expression of some genes (ELIP, Chaperonin 20). However, at 42/34°C a tolerance threshold was reached, mostly in the 380-plants and Icatu. Adjustments in raffinose, lutein, β-carotene, α-tocopherol and HSP70 pools, and the upregulated expression of genes related to protective (ELIPS, HSP70, Chape 20, and 60) and antioxidant (CAT, CuSOD2, APX Cyt, APX Chl) proteins were largely driven by temperature. However, enhanced [CO2] maintained higher activities of GR (Icatu) and CAT (Icatu and IPR108), kept (or even increased) the Cu,Zn-SOD, APX, and CAT activities, and promoted a greater upregulation of those enzyme genes, as well as those related to HSP70, ELIPs, Chaperonins in CL153, and Icatu. These changes likely favored the maintenance of reactive oxygen species (ROS) at controlled levels and contributed to mitigate of photosystem II photoinhibition at the highest temperature. Overall, our results highlighted the important role of enhanced [CO2] on the coffee crop acclimation and sustainability under predicted future global warming scenarios.

A New Test of Copper and Zinc Abundances in Late-Type Stars Using Cu II and Zn II lines in the Near-Ultraviolet

NASA Astrophysics Data System (ADS)

Roederer, Ian

2017-08-01

The copper (Cu, Z = 29) and zinc (Zn, Z = 30) abundances found in late-type stars provide critical constraints on models that predict the yields of massive star supernovae, hypernovae, Type Ia supernovae, and AGB stars, which are essential ingredients in Galactic chemical evolution models. Furthermore, Zn is commonly used to compare the abundance of iron-group elements in the gas phase in high-redshift DLA systems with metallicities in Local Group stars. It is thus important that the observational Cu and Zn abundances in stars are correct. My proposed archive study will address this issue by using archive STIS spectra of 14 stars to provide the first systematic observational tests of non-LTE calculations of Cu and Zn line formation in late-type stars. The non-LTE calculations predict that all LTE [Cu/Fe] abundance ratios presently found in the literature are systematically lower than the true ratios found in stars. The non-LTE calculations for Zn predict that the LTE values in the literature may be systematically overestimated in low-metallicity stars. The LTE abundances of Cu and Zn are derived from Cu I and Zn I lines. The key advance enabled by the use of NUV spectra is the detection of several lines of Cu II and Zn II, which cannot be detected in the optical or infrared. Cu II and Zn II are largely immune to non-LTE effects in the atmospheres of late-type stars. The metallicities of the 14 stars with NUV spectra span -2.6 < [Fe/H] < -0.1, which covers the range of most Cu and Zn abundances reported in the literature. The proposed study will allow me to test the non-LTE calculations and calibrate the stellar abundances.

Influence of Li Addition to Zn-Al Alloys on Cu Substrate During Spreading Test and After Aging Treatment

NASA Astrophysics Data System (ADS)

Gancarz, Tomasz; Pstrus, Janusz; Cempura, Grzegorz; Berent, Katarzyna

2016-12-01

The spreading of Zn-Al eutectic-based alloys with 0.05 wt.%, 0.1 wt.%, and 0.2 wt.% Li on Cu substrate has been studied using the sessile drop method in presence of QJ201 flux. Wetting tests were performed after 1 min, 3 min, 8 min, 15 min, 30 min, and 60 min of contact at temperatures of 475°C, 500°C, 525°C, and 550°C. Samples after spreading at 500°C for 1 min were subjected to aging for 1 day, 10 days, and 30 days at temperature of 120°C, 170°C, and 250°C. The spreadability of eutectic Zn-5.3Al alloy with different Li contents on Cu substrate was determined in accordance with ISO 9455-10:2013-03. Selected solidified solder-substrate couples were, after spreading and aging tests, cross-sectioned and subjected to scanning electron microscopy, energy-dispersive spectroscopy (EDS), and x-ray diffraction (XRD) analysis of the interfacial microstructure. An experiment was designed to demonstrate the effect of Li addition on the kinetics of the formation and growth of CuZn, Cu5Zn8, and CuZn4 intermetallic compound (IMC) phases, during spreading and aging. The IMC layers formed at the interface were identified using XRD and EDS analyses. Increasing addition of Li to Zn-Al alloy caused a reduction in the thickness of the IMC layer at the interface during spreading, and an increase during aging. The activation energy was calculated, being found to increase for the Cu5Zn8 phase but decrease for the CuZn and CuZn4 phases with increasing Li content in the Zn-Al-Li alloys. The highest value of 142 kJ mol-1 was obtained for Zn-Al with 1.0 Li during spreading and 69.2 kJ mol-1 for Zn-Al with 0.05 Li during aging. Aging at 250°C caused an increase in only the Cu5Zn8 layer, which has the lowest Gibbs energy in the Cu-Zn system. This result is connected to the high diffusion of Cu from the substrate to the solder.

Effect of the transit through the gut of earthworm (Eisenia fetida) on fractionation of Cu and Zn in pig manure.

PubMed

Li, Lingxiangyu; Wu, Jianyang; Tian, Guangming; Xu, Zhenlan

2009-08-15

To investigate the effect of the transit through the gut of earthworm (Eisenia fetida) on the fractionation of Cu and Zn in pig manure, earthworms were reared with pig manure in the greenhouse. Both the pig manure and the earthworm casts were subjected to a five-step sequential extraction of Cu and Zn. The content of Cu bound to organic matter in pig manure increased from 60% to 75% after transit through the gut of earthworm, whereas that of Zn decreased from 50% to 25%. It demonstrated that Cu had a strong affinity towards organic matter. The share of Cu and Zn in the exchangeable fraction was reduced by the transit through the gut of earthworm. Based on these changes, Cu was more bioavailable, whereas Zn was less bioavailable. The factors affecting metal fractionation, like pH, organic matter (OM) and total phosphorous (TP) contents, and total metal concentration, were also affected significantly by the transit through the gut of earthworm. Stepwise multiple regression analysis revealed that the fractionation of Cu in the earthworm casts was influenced by OM, TP and the amount of Cu in the earthworm casts. The total Zn concentration in the earthworm casts was the primary factor that explained most of the variation in Zn fractionation. The present study demonstrated that the digestive activity in the gut of E. fetida played an important role in the fraction redistribution of Cu and Zn in pig manure.

Reduced anti-ferromagnetism promoted by Zn 3d 10 substitution at CuO 2 planar sites of Cu 0.5Tl 0.5Ba 2Ca 3Cu 4O 12-δ superconductors

NASA Astrophysics Data System (ADS)

Mumtaz, M.; Khan, Nawazish A.

2009-11-01

The role of charge carriers in ZnO 2/CuO 2 planes of Cu 0.5Tl 0.5Ba 2Ca 3Cu 4-yZn yO 12-δ material in bringing about superconductivity has been explained. Due to suppression of anti-ferromagnetic order with Zn 3d 10 ( S=0) substitution at Cu 3d 9(S={1}/{2}) sites in the inner CuO 2 planes of Cu 0.5Tl 0.5Ba 2Ca 3Cu 4O 12-δ superconductor, the distribution of charge carriers becomes homogeneous and optimum, which is evident from the enhanced superconductivity parameters. The decreased c-axis length with the increase of Zn doping improves interlayer coupling and hence the three dimensional (3D) conductivity in the unit cell is enhanced. Also the softening of phonon modes with the increased Zn doping indicates that the electron-phonon interaction has an essential role in the mechanism of high- Tc superconductivity in these compounds.

Molecular and biochemical characterization of a unique mutation in CCS, the human copper chaperone to superoxide dismutase.

PubMed

Huppke, Peter; Brendel, Cornelia; Korenke, Georg Christoph; Marquardt, Iris; Donsante, Anthony; Yi, Ling; Hicks, Julia D; Steinbach, Peter J; Wilson, Callum; Elpeleg, Orly; Møller, Lisbeth Birk; Christodoulou, John; Kaler, Stephen G; Gärtner, Jutta

2012-08-01

Copper (Cu) is a trace metal that readily gains and donates electrons, a property that renders it desirable as an enzyme cofactor but dangerous as a source of free radicals. To regulate cellular Cu metabolism, an elaborate system of chaperones and transporters has evolved, although no human Cu chaperone mutations have been described to date. We describe a child from a consanguineous family who inherited homozygous mutations in the SLC33A1, encoding an acetyl CoA transporter, and in CCS, encoding the Cu chaperone for superoxide dismutase. The CCS mutation, p.Arg163Trp, predicts substitution of a highly conserved arginine residue at position 163, with tryptophan in domain II of CCS, which interacts directly with superoxide dismutase 1 (SOD1). Biochemical analyses of the patient's fibroblasts, mammalian cell transfections, immunoprecipitation assays, and Lys7Δ (CCS homolog) yeast complementation support the pathogenicity of the mutation. Expression of CCS was reduced and binding of CCS to SOD1 impaired. As a result, this mutation causes reduced SOD1 activity and may impair other mechanisms important for normal Cu homeostasis. CCS-Arg163Trp represents the primary example of a human mutation in a gene coding for a Cu chaperone. © 2012 Wiley Periodicals, Inc.

Synergies between Unsaturated Zn/Cu Doping Sites in Carbon Dots Provide New Pathways for Photocatalytic Oxidation

DOE PAGES

Wu, Wenting; Zhang, Qinggang; Wang, Ruiqin; ...

2017-12-07

Unsaturated metal species (UMS) confined in nanomaterials play important roles for electron transfer in a wide range of catalytic reactions. However, the limited fabrication methods of UMS restrict their wider catalytic applications. Here in this paper, we report on the synergy of unsaturated Zn and Cu dopants confined in carbon dots (ZnCu-CDs) to produce enhanced electron transfer and photooxidation processes in the doped CDs. The Zn/Cu species chelate with the carbon matrix mainly through Cu-O(N)-Zn-O(N)-Cu complexes. Within this structure, Cu 2+ acts as a mild oxidizer that facilely increases the unsaturated Zn content and also precisely tunes the unsaturated Znmore » valence state to Zn d+, where d is between 1 and 2, instead of Zn. With the help of UMS, electron-transfer pathways are produced, enhancing both the electron donating (7.0 times) and-accepting (5.3 times) abilities relative to conventional CDs. Because of these synergistic effects, the photocatalytic efficiency of CDs in photooxidation reactions is shown to improve more than 5-fold.« less

Potential effect of CuInS2/ZnS core-shell quantum dots on P3HT/PEDOT:PSS heterostructure based solar cell

NASA Astrophysics Data System (ADS)

Jindal, Shikha; Giripunje, S. M.

2018-07-01

Nanostructured quantum dots (QDs) are quite promising in the solar cell application due to quantum confinement effect. QDs possess multiple exciton generation and large surface area. The environment friendly CuInS2/ZnS core-shell QDs were prepared by solvothermal method. Thus, the 3 nm average sized CuInS2/ZnS QDs were employed in the bulk heterojunction device and the active blend layer consisting of the P3HT and CuInS2/ZnS QDs was investigated. The energy level information of CuInS2/ZnS QDs as an electron acceptor was explored by ultra violet photoelectron spectroscopy. Bulk heterojunction hybrid device of ITO/PEDOT:PSS/P3HT: (CuInS2/ZnS QDs)/ZnO/Ag was designed by spin coating approach and its electrical characterization was investigated by solar simulator. Current density - voltage characteristics shows the enhancement in power conversion efficiency with increasing concentration of CuInS2/ZnS QDs in bulk heterojunction device.

Comparison of Cu2+ and Zn2+ thermalcatalyst in treating diazo dye

NASA Astrophysics Data System (ADS)

Lau, Y. Y.; Wong, Y. S.; Ong, S. A.; Lutpi, N. A.; Ho, L. N.

2018-05-01

This research demonstrates the comparison between copper (II) sulphate (CuSO4) and zinc oxide (ZnO) as thermalcatalysts in thermolysis process for the treatment of diazo reactive black 5 (RB 5) wastewater. CuSO4 was found to be the most effective thermalcatalyst in comparison to ZnO. The color removal efficiency of RB 5 catalysed by CuSO4 and ZnO were 91.55 % at pH 9.5 and 7.36 % at pH 2, respectively. From the UV-Vis wavelength scan, CuSO4 catalyst is able to cleave the molecular structure bonding more efficiently compared to ZnO. ZnO which only show a slight decay on the main chemical network strands: azo bond, naphthalene and benzene rings whereas CuSO4 catalyst is able to fragment azo bond and naphthalene more effectively. The degradation reactions of CuSO4 and ZnO as thermalcatalysts in thermolysis process were compared.

Toxicity of nanoparticles of CuO, ZnO and TiO2 to microalgae Pseudokirchneriella subcapitata.

PubMed

Aruoja, Villem; Dubourguier, Henri-Charles; Kasemets, Kaja; Kahru, Anne

2009-02-01

Toxicities of ZnO, TiO2 and CuO nanoparticles to Pseudokirchneriella subcapitata were determined using OECD 201 algal growth inhibition test taking in account potential shading of light. The results showed that the shading effect by nanoparticles was negligible. ZnO nanoparticles were most toxic followed by nano CuO and nano TiO2. The toxicities of bulk and nano ZnO particles were both similar to that of ZnSO4 (72 h EC50 approximately 0.04 mg Zn/l). Thus, in this low concentration range the toxicity was attributed solely to solubilized Zn2+ ions. Bulk TiO2 (EC50=35.9 mg Ti/l) and bulk CuO (EC50=11.55 mg Cu/l) were less toxic than their nano formulations (EC50=5.83 mg Ti/l and 0.71 mg Cu/l). NOEC (no-observed-effect-concentrations) that may be used for risk assessment purposes for bulk and nano ZnO did not differ (approximately 0.02 mg Zn/l). NOEC for nano CuO was 0.42 mg Cu/l and for bulk CuO 8.03 mg Cu/l. For nano TiO2 the NOEC was 0.98 mg Ti/l and for bulk TiO2 10.1 mg Ti/l. Nano TiO2 formed characteristic aggregates entrapping algal cells that may contribute to the toxic effect of nano TiO2 to algae. At 72 h EC50 values of nano CuO and CuO, 25% of copper from nano CuO was bioavailable and only 0.18% of copper from bulk CuO. Thus, according to recombinant bacterial and yeast Cu-sensors, copper from nano CuO was 141-fold more bioavailable than from bulk CuO. Also, toxic effects of Cu oxides to algae were due to bioavailable copper ions. To our knowledge, this is one of the first systematic studies on effects of metal oxide nanoparticles on algal growth and the first describing toxic effects of nano CuO towards algae.

Evidences for Cu and Zn Isotope Fractionation in Sediments and Particulate Suspended Matter of the Scheldt Estuary

NASA Astrophysics Data System (ADS)

Petit, J.; Mattielli, N.; de Jong, J.; Chou, L.

2004-05-01

Recent developments in MC-ICP-MS technology allow high precision measurements of heavy stable isotopes, such as Cu and Zn isotopes, which have been shown to undergo biotic or abiotic fractionation (1). Application of Zn isotopes to the study of aquatic ecosystems has already shown some interesting perspectives in their potential use as biogeochemical tracers in deep ocean carbonates (2) or Fe-Mn nodules (3). However, until now no investigation of possible Cu and Zn isotopic fractionation has been carried out within estuaries that are important pathways for hydrological and geochemical cycling of metals. Cu and Zn isotope geochemistry has been studied in sandy to loamy surface sediments (top 20 cm) and in suspended particulate matter (SPM) along a transect in a strong tidal estuary, the Scheldt estuary situated in Belgium and the Netherlands (November 2002). Further to separation of Cu, Fe and Zn by one step ion-exchange chromatography, Cu and Zn isotopic ratios are measured with a "Nu-Plasma" MC-ICP-MS. Instrumental mass bias is corrected using reference materials (Zn JMC, Cu NIST SRM 976 and Ga JMC standard) by simultaneous standard-sample bracketing and external normalization (500 ppb Zn doping for Cu isotopic analyses in static mode and 250 ppb Ga doping for Zn isotopic analyses in dynamic mode), together with a Ni correction. These methods lead to long-term reproducibility (2σ at 95 % confidence level) of ± 0.07 per mil for δ 66Zn (n=100 over 7 analysis sessions) and ± 0.06 per mil for δ 65Cu (n=120 over 8 analysis sessions) for 500 ppb of reference material. Average beam intensities are 6 V/ppm. Precise and reproducible results are obtained for concentration as low as 100 ppb for Cu and Zn. Expected Cu and Zn enrichment in SPM (120 ppm and 1200 ppm respectively) and sediments (being 6 to 10 times lower than SPM) in the upper estuary and progressive decrease in metal content by mixing downstream of the maximum turbidity zone (MTZ, around 5 psu) are observed. Results show that variations in Cu and Zn isotopic composition are smaller in SPM (δ 66Zn varying from 0.35 to 0.17 and δ 65Cu from -0.13 to 0.18) than in sediments. Cu and Zn isotopic signatures of sediments show a clear trend of lighter isotopes removal from the MTZ seaward with δ 66Zn varying from 0.21 at 2 psu to 1.11 per mil at 33 psu (and δ 65Cu = -0.37 to 0.24). In contrast, Zn isotopic compositions in SPM are more homogeneous with average δ 66Zn of 0.24 ± 0.18 over all the transect. Cu isotopic composition in SPM are very constant downstream of the MTZ with average δ 65Cu =-0.06 ± 0.08 but become more scattered within MTZ (varying from -0.04 to 0.18). These preliminary results pinpoint important variations in Cu and Zn isotopic compositions within estuarine systems and contrasted isotopic signatures in Cu and Zn between SPM and sediments. Results suggest the important role of early diagenesis in the isotope geochemistry of heavy metals in estuarine environment. This study provides a stepping stone for further investigation of interacting processes involved in controlling the cycling of metals in the Scheldt estuary. (1) Zhu et al., Earth Planet. Sci. Lett. 200 (2002), 47-62 (2) Pichat et al., Earth Planet. Sci. Lett. 6598 (2003), 1-12 (3) Maréchal et al., Geochem. Geophys. Geosyt., 1 (2000), GC000029

Fe{sub 3}O{sub 4}/CuO/ZnO/Nano graphene platelets (Fe{sub 3}O{sub 4}/CuO/ZnO/NGP) composites prepared by sol-gel method with enhanced sonocatalytic activity for the removal of dye

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hendry, Tju; Taufik, Ardiansyah; Saleh, Rosari, E-mail: rosari.saleh@gmail.com, E-mail: rosari.saleh@ui.ac.id

2016-04-19

In this study, an attempt has been made to synthesize nanographene platelets coupled with Fe3O4/CuO/ZnO (Fe3O4/CuO/ZnO/NGP) with various ZnO loadings using a two step methods, sol-gel followed by hydrothermal method. Characterization was carried out by X-ray diffraction, energy-dispersive X-ray spectroscopy and vibrating sample magnetometer. The sonocatalytic performance was evaluated by degradation of methylene blue under ultrasonic irradiation.The Fe3O4/CuO/ZnO/NGP showed superior sonocatalytic activity than the Fe3O4/CuO/ZnO materials. They also showed high stability and can be easily separated from the reaction system for recycling process.

Electronic absorption band broadening and surface roughening of phthalocyanine double layers by saturated solvent vapor treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jinhyun; Yim, Sanggyu, E-mail: sgyim@kookmin.ac.kr

2012-10-15

Variations in the electronic absorption (EA) and surface morphology of three types of phthalocyanine (Pc) thin film systems, i.e. copper phthalocyanine (CuPc) single layer, zinc phthalocyanine (ZnPc) single layer, and ZnPc on CuPc (CuPc/ZnPc) double layer film, treated with saturated acetone vapor were investigated. For the treated CuPc single layer film, the surface roughness slightly increased and bundles of nanorods were formed, while the EA varied little. In contrast, for the ZnPc single layer film, the relatively high solubility of ZnPc led to a considerable shift in the absorption bands as well as a large increase in the surface roughnessmore » and formation of long and wide nano-beams, indicating a part of the ZnPc molecules dissolved in acetone, which altered their molecular stacking. For the CuPc/ZnPc film, the saturated acetone vapor treatment resulted in morphological changes in mainly the upper ZnPc layer due to the significantly low solubility of the underlying CuPc layer. The treatment also broadened the EA band, which involved a combination of unchanged CuPc and changed ZnPc absorption.« less

In Situ Subcellular Imaging of Copper and Zinc in Contaminated Oysters Revealed by Nanoscale Secondary Ion Mass Spectrometry.

PubMed

Weng, Nanyan; Jiang, Haibo; Wang, Wen-Xiong

2017-12-19

Determining the in situ localization of trace elements at high lateral resolution levels in the biological system is very challenging, but critical for our understanding of metal sequestration and detoxification. Here, the cellular and subcellular distributions of Cu and Zn in contaminated oysters of Crassostrea hongkongensis were for the first time mapped using nanoscale secondary ion mass spectrometry (nanoSIMS). Three types of metal-containing cells were revealed in the gill and mantle of oysters, including Cu-specific hemocytes, Cu and Zn-containing granular hemocytes, and Cu and Zn-containing calcium cells. Obvious intercellular distribution of Cu was found in the gill tissue, indicating the potential role of hemolymph in the transportation of Cu in oysters. The distribution of Cu showed a strong colocalization with sulfur and nitrogen in Cu-specific hemocyte and intercellular hemolymph. In the Cu and Zn-containing granular hemocytes and calcium cells, the co-occurrence of Cu and Zn with phosphorus and calcium was also found. Different relationships of distributions between Cu/Zn and macronutrient elements (nitrogen, sulfur and phosphorus) implied the differential metal complexation in oysters. Interestingly, quantitative analysis of the ratios of 32 S - / 12 C 14 N - and 31 P - / 12 C 14 N - of metal-deposited sites suggested the dynamic process of transfer of Cu and Zn from the metabolized protein pool to a more thermodynamically stable and detoxified form.

Facile synthesis and photocatalytic activity of bi-phase dispersible Cu-ZnO hybrid nanoparticles

NASA Astrophysics Data System (ADS)

Liu, Xiao; Liu, HongLing; Zhang, WenXing; Li, XueMei; Fang, Ning; Wang, XianHong; Wu, JunHua

2015-04-01

Bi-phase dispersible Cu-ZnO hybrid nanoparticles were synthesized by one-pot non-aqueous nanoemulsion with the use of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO-PPO-PEO) as the surfactant. The transmission electron microscopy (TEM) and X-ray diffraction (XRD) show high crystallinity of the Cu-ZnO hybrid nanoparticles and an average particle size of ~19.4 nm. The ultraviolet-visible light absorbance spectrometry (UV-vis) and photoluminescence spectrophotometry (PL) demonstrate well dispersibility and excellent optical performance of Cu-ZnO hybrid nanoparticles both in organic and aqueous solvent. The X-ray photoelectron spectroscopy (XPS) confirms Cu1+ and Cu2+ in ZnO. The observation using Sudan red (III) as probe molecule reveals that the Cu-ZnO hybrid nanoparticles possess enhanced photocatalytic activity and stability which are promising for potential applications in photocatalysis.

Solar Absorber Cu 2 ZnSnS 4 and its Parent Multilayers ZnS/SnS 2 /Cu 2 S Synthesized by Atomic Layer Deposition and Analyzed by X-ray Photoelectron Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baryshev, Sergey V.; Riha, Shannon C.; Zinovev, Alexander V.

2015-06-01

Presented here are results of x-ray photoelectron spectroscopy (XPS) on multilayers of metal-sulfide binaries ZnS, SnS2, and Cu2S grown by atomic layer deposition (ALD) on Si substrates, and of Cu2ZnSnS4 (CZTS) formed upon 450 °C annealing of the parent multilayer ZnS/SnS2/Cu2S. Survey and detailed spectral analysis of the multilayer ZnS/SnS2/Cu2S are presented step-wise, as each layer was sequentially added by ALD. The set of data is finalized with spectra of the resulting alloy CZTS. XPS analyses indicate significant mixing between SnS2 and Cu2S, which favors CZTS formation within the ALD approach.

ZnCuInS/ZnSe/ZnS quantum dot-based downconversion light-emitting diodes and their thermal effect

DOE PAGES

Liu, Wenyan; Zhang, Yu; Wang, Dan; ...

2015-08-13

The quantum dot-based light-emitting diodes (QD-LEDs) were fabricated using blue GaN chips and red-, yellow-, and green-emitting ZnCuInS/ZnSe/ZnS QDs. The power efficiencies were measured as 14.0 lm/W for red, 47.1 lm/W for yellow, and 62.4 lm/W for green LEDs at 2.6 V. The temperature effect of ZnCuInS/ZnSe/ZnS QDs on these LEDs was investigated using CIE chromaticity coordinates, spectral wavelength, full width at half-maximum (FWHM) and power efficiencies (PE). The thermal quenching induced by the increased surface temperature of the device was confirmed to be one of the important factors to decrease power efficiencies while the CIE chromaticity coordinates changed littlemore » due to the low emission temperature coefficients of 0.022, 0.050 and 0.068 nm/°C for red-, yellow- and green-emitting ZnCuInS/ZnSe/ZnS QDs. Lastly this indicates that ZnCuInS/ZnSe/ZnS QDs are more suitable for down-conversion LEDs compared to CdSe QDs.« less

Chemical Synthesis of ZnS:Cu Nanosheets

NASA Astrophysics Data System (ADS)

Bodo, Bhaskarjyoti; Kalita, P. K.

2010-10-01

ZnS thin films are synthesized through chemical bath deposition (CBD) technique from aqueous solution of ZnSO4 and thiourea mixing in equal volume and equimolar ratio. A 1% CuSO4 solution is mixed with the ZnSO4 solution for doping before the final chemical reaction. SEM image shows the formation of mainly nanosheets, teeth and comb like structures. Absorption studies show red shift of enhanced band gap on Cu doping. Photoluminescence of ZnS:Cu reveals the enhancement of blue luminescence at 468 nm and low intensity green emission at 493 nm which is attributed to more Cu2+ lying in the interstices. XRD shows that the prepared ZnS nanophosphors possess cubic zinc blende structures.

High figure-of-merit p-type transparent conductor, Cu alloyed ZnS via radio frequency magnetron sputtering

NASA Astrophysics Data System (ADS)

Maurya, Sandeep Kumar; Liu, Ya; Xu, Xiaojie; Woods-Robinson, Rachel; Das, Chandan; Ager, Joel W., III; Balasubramaniam, K. R.

2017-12-01

p-type transparent conducting Cu alloyed ZnS thin films from Cu{x} Zn{1-x} S targets (x = 0.1 , 0.2, 0.3, 0.4, and 0.5) were deposited on glass substrates via radio frequency sputtering. x-ray diffraction and TEM-SAED analysis show that all the films have sphalerite ZnS as the majority crystalline phase. In addition, films with 30% and 40% Cu show the presence of increasing amounts of crystalline Cu2S phase. Conductivity values  ⩾400 S cm-1 were obtained for the films having 30% and 40% Cu, with the maximum conductivity of 752 S cm-1 obtained for the film with 40% Cu. Temperature dependent electrical transport measurements indicate metallic as well as degenerate hole conductivity in the deposited films. The reflection-corrected transmittance of this Cu alloyed ZnS (40% Cu) film was determined to be  ⩾75% at 550 nm. The transparent conductor figure of merit (ΦTC ) of the Cu alloyed ZnS (40% Cu), calculated with the average value of transmittance between 1.5 to 2.5 eV, was  ≈276 μS .

Influence of Cu Addition on the Structure, Mechanical and Corrosion Properties of Cast Mg-2%Zn Alloy

NASA Astrophysics Data System (ADS)

Lotfpour, M.; Emamy, M.; Dehghanian, C.; Tavighi, K.

2017-05-01

Effects of different concentrations of Cu on the structure, mechanical and corrosion properties of Mg-2%Zn alloy were studied by the use of x-ray diffraction, optical microscopy, scanning electron microscopy, energy dispersive spectroscopy, standard tensile testing, polarization and electrochemical impedance spectroscopy (EIS) measurements. The average grain size of the alloy decreased from above 1000 μm to about 200 μm with 5 wt.% Cu addition in as-cast condition. Microstructural studies revealed that Mg-2Zn- xCu alloys matrix typically consists of primary α-Mg and MgZnCu and Mg(Zn,Cu)2 intermetallics which are mainly found at the grain boundaries. The results obtained from mechanical testing ascertained that Cu addition increased the hardness values significantly. Although the addition of 0.5 wt.% Cu improved the ultimate tensile strength and elongation values, more Cu addition (i.e., 5 wt.%) weakened the tensile properties of the alloy by introducing semi-continuous network of brittle intermetallic phases. Based on polarization test results, it can be concluded that Cu eliminates a protective film on Mg-2%Zn alloy surface. Among Mg-2%Zn- x%Cu alloys, the one containing 0.1 wt.% Cu exhibited the best anti-corrosion property. However, further Cu addition increased the volume fraction of intermetallics culminating in corrosion rate enhancement due to the galvanic couple effect. EIS and microstructural analysis also confirmed the polarization results.

Lipid peroxidation and antioxidant status in colorectal cancer

PubMed Central

Skrzydlewska, Elzbieta; Sulkowski, Stanislaw; Koda, Mariusz; Zalewski, Bogdan; Kanczuga-Koda, Luiza; Sulkowska, Mariola

2005-01-01

AIM: Reactive oxygen species (ROS) can induce carcinogenesis via DNA injury. Both enzymatic and non-enzymatic parameters participate in cell protection against harmful influence of oxidative stress. The aim of the present study was to assess the levels of final lipid peroxidation products like malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) in primary colorectal cancer. Moreover, we analysed the activity of main antioxidative enzymes, superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSRG-R) and the level of non-enzymatic antioxidants (glutathione, vitamins C and E). METHODS: Investigations were conducted in 81 primary colorectal cancers. As a control, the same amount of sample was collected from macroscopically unchanged colon regions of the most distant location to the cancer. Homogenisation of specimens provided 10% homogenates for our evaluations. Activity of antioxidant enzymes and level of glutathione were determined by spectrophotometry. HPLC revealed levels of vitamins C and E and served as a method to detect terminal products of lipid peroxidation in colorectal cancer. RESULTS: Our studies demonstrated a statistically significant increase in the level of lipid peroxidation products (MDA-Adc.muc.-2.65±0.48 nmol/g, Adc.G3-2.15±0.44 nmol/g, clinical IV stage 4.04±0.47 nmol/g, P<0.001 and 4-HNE-Adc.muc. -0.44±0.07 nmol/g, Adc.G3-0.44±0.10 nmol/g, clinical IV stage 0.52±0.11 nmol/g, P<0.001) as well as increase of Cu,Zn-SOD (Adc.muc.-363±72 U/g, Adc.G3-318±48 U/g, clinical IV stage 421±58 U/g, P<0.001), GSH-Px (Adc.muc. -2143±623 U/g, Adc.G3-2005±591 U/g, clinical IV stage 2467±368 U/g, P<0.001) and GSSG-R (Adc.muc.-880±194 U/g, Adc.G3-795±228 U/g, clinical IV stage 951±243 U/g, P<0.001) in primary tumour comparison with normal colon (MDA-1.39±0.15 nmol/g, HNE-0.29±0.03 nmol/g, Cu, Zn-SOD-117±25 U/g, GSH-Px-1723±189 U/g, GSSG-R-625±112 U/g) especially in mucinous and G3-grade adenocarcinomas as well as clinical IV stage of colorectal cancer. We also observed a decrease of CAT activity (Adc.muc. -40±14 U/g, clinical IV stage 33±18 U/g vs 84±17 U/g, P<0.001) as well as a decreased level of reduced glutathione (clinical IV stage 150±48 nmol/g vs 167±15 nmol/g, P<0.05) and vitamins C and E (vit. C-clinical IV stage 325±92 nmol/g vs 513±64 nmol/g, P<0.001; vit. E-clinical IV stage 13.3±10.3 nmol/g vs 37.5±5.2 nmol/g). CONCLUSION: Colorectal carcinogenesis is associated with serious oxidative stress and confirms that gradual advancement of oxidative-antioxidative disorders is followed by progression of colorectal cancer. PMID:15637754

Green synthesis of CuInS2/ZnS core-shell quantum dots by facile solvothermal route with enhanced optical properties

NASA Astrophysics Data System (ADS)

Jindal, Shikha; Giripunje, Sushama M.; Kondawar, Subhash B.; Koinkar, Pankaj

2018-03-01

We report an eco-friendly green synthesis of highly luminescent CuInS2/ZnS core-shell quantum dots (QDs) with average particle size ∼ 3.9 nm via solvothermal process. The present study embodies the intensification of CuInS2/ZnS QDs properties by the shell growth on the CuInS2 QDs. The as-prepared CuInS2 core and CuInS2/ZnS core-shell QDs have been characterized using a range of optical and structural techniques. By adopting a low temperature growth of CuInS2 core and high temperature growth of CuInS2/ZnS core-shell growth, the tuning of absorption and photoluminescence emission spectra were observed. Optical absorption and photoluminescence spectroscopy probe the effect of ZnS passivation on the electronic structure of the CuInS2 dots. In addition, QDs have been scrutinized using ultra violet photoelectron spectroscopy (UPS) to explore their electronic band structure. The band level positions of CuInS2 and CuInS2/ZnS QDs suffices the demand of non-toxic acceptor material for electronic devices. The variation in electronic energy levels of CuInS2 core with the coating of wide band gap ZnS shell influence the removal of trap assisted recombination on the surface of the core. QDs exhibited tunable emission from red to orange region. These studies reveal the feasibility of QDs in photovoltaic and light emitting diodes.

Effects of Zn²⁺ and Cu²⁺ on loach ovaries and ova development.

PubMed

Tang, Jian-Xun; Li, Jun-Rong; Liu, Zhong-Liang; Zhao, Hua; Tao, Xiao-Min; Cheng, Zhang-Shun

2013-10-01

This study compared the accumulation of Zn²⁺ and Cu²⁺ in the ovaries and ova of loaches under different concentrations of Zn²⁺ (1.00, 2.50 and 5.00 mg/L respectively) and Cu²⁺ (0.10, 0.25 and 0.50 mg/L respectively). The results showed that both Zn²⁺ and Cu²⁺ accumulated in the ovaries, and that the relationship between accumulation and time was linear over 20 days of exposure. The accumulation of the metals in ovaries was closely related to the concentration of exposure in the solutions (P<0.05), and was obviously affected by the time and doses. However, the Cu²⁺ concentration was significantly higher than Zn²⁺ (P<0.05). The development level of ova in the ovaries also correlated with the concentration and exposure period in the Zn²⁺ and Cu²⁺ solutions. This study compared the accumulation of Zn 2+ and Cu 2+ in the ovaries and ova of loaches under different concentrations of Zn 2+ (1.00, 2.50 and 5.00 mg/L respectively) and Cu 2+ (0.10, 0.25 and 0.50 mg/L respectively). The results showed that both Zn 2+ and Cu 2+ accumulated in the ovaries, and that the relationship between accumulation and time was linear over 20 days of exposure. The accumulation of the metals in ovaries was closely related to the concentration of exposure in the solutions ( P< 0.05), and was obviously affected by the time and doses. However, the Cu 2+ concentration was significantly higher than Zn 2+ ( P< 0.05). The development level of ova in the ovaries also correlated with the concentration and exposure period in the Zn 2+ and Cu 2+ solutions.

Synthesis of Cu{sub 2}ZnSnS{sub 4} nanoparticles and controlling the morphology with polyethylene glycol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rawat, Kusum; Department of Electronic Science, University of Delhi South Campus, Delhi 110021; Kim, Hee-Joon

Highlights: • Cu{sub 2}ZnSnS{sub 4} nanoparticles were synthesized by wet chemical technique. • First report on the effect of using polyethylene glycol as a structure directing agent on Cu{sub 2}ZnSnS{sub 4} nanoparticles. • The morphology of Cu{sub 2}ZnSnS{sub 4} nanoparticles changes into nanoflakes and nanorods structures with polyethylene glycol concentration. • Polyethylene glycol assisted Cu{sub 2}ZnSnS{sub 4} nanoparticle film exhibits optical bandgap of 1.5 eV which is suitable for the application in solar cells. - Abstract: Cu{sub 2}ZnSnS{sub 4} nanoparticles were synthesized by wet chemical technique using metal thiourea precursor at 250 °C. The structural and morphological properties of asmore » grown nanoparticles have been characterized by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and transmission electron microscopy. The influence of different concentration of polyethylene glycol as structure directing agent on the morphologies of Cu{sub 2}ZnSnS{sub 4} nanoparticles are investigated on thin films deposited by spin coating technique. The mean crystallite size of the Cu{sub 2}ZnSnS{sub 4} nanoparticles was found to improve with polyethylene glycol concentration. Scanning electron microscopy images of Cu{sub 2}ZnSnS{sub 4} revealed aggregated spherical shaped nanoparticles whereas the polyethylene glycol assisted Cu{sub 2}ZnSnS{sub 4} nanoparticle films show nanoflakes and nanorods structures with increasing concentration of polyethylene glycol. Transmission electron microscopy analysis has also been performed to determine the size and structure of nanorods. UV–vis absorption spectroscopy shows the broad band absorption with optical bandgap of 1.50 eV for polyethylene glycol assisted Cu{sub 2}ZnSnS{sub 4} films.« less

Flavonoids with DNA strand-scission activity from Rhus javanica var. roxburghiana.

PubMed

Lin, Chun-Nan; Chen, Hui-Ling; Yen, Ming-Hong

2008-01-01

The flavonoids isolated from the stems of Rhus javanica var. roxburghiana, taxifolin (1), fisetin (2), fustin (3), 3,7,4'-trihydroxyflavanone (4) and 3,7,4'-trihydroxyflavone (5) caused breakage of supercoiled plasmid pBR322 DNA in the presence of Cu(II). Cu(I) was shown to be an essential intermediate by using the Cu(I)-specific sequestering reagent neocuproine. The Cu(II)-mediated DNA scissions induced by 1, 2, 3 and 5 were inhibited by the addition of catalase and exhibited DNA strand break by the addition of KI and superoxide dimutase (SOD), while in the Cu(II)-mediated DNA scissions induced by 4 was inhibited by the addition of KI, SOD, and catalase. It is concluded that 1, 2, 3, and 5 can induce H2O2 and superoxide anion, while 4 can induce OH* and H2O2 and subsequent oxidative damage of DNA in the presence of Cu(II).

Excess copper induces anoxygenic photosynthesis in Anabaena doliolum: a homology based proteomic assessment of its survival strategy.

PubMed

Bhargava, Poonam; Mishra, Yogesh; Srivastava, Ashish Kumar; Narayan, Om Prakash; Rai, Lal Chand

2008-04-01

This study is the first to demonstrate operation of anoxygenic photosynthesis in copper acclimated Anabaena doliolum and to offer proteomic comparison with the control cells. The Cu-treated control strain showed a negative correlation in growth and intracellular Cu, partial inhibition of O(2)-evolution, PS II, PS I, whole chain, chlorophyll absorption, and nitrogenase activity. However, the acclimated strain growing in 250-fold excess Cu exhibited near normal growth, ATP content, PS I activity, carbon fixation, and almost complete inhibition of O(2)-evolution, PS II and chlorophyll absorption, but increased nitrogenase activity as compared to control. Proteomic decoding of the survival strategy of Cu-treated control and the acclimated strain using two-dimensional gel electrophoresis and MALDI-TOF MS analysis of proteins displaying significant and reproducible changes demonstrated involvement of transketolase, phycoerythrocyanin alpha-chain, iron superoxide dismutase (Fe-SOD), hypothetical protein alr 0803, manganese superoxide dismutase (Mn-SOD), phosphoribulokinase, and plastocyanin (PLC). Expression pattern of these proteins was attested at the transcriptional level using RT-PCR. Time course analysis of proteins of Cu-treated control strain revealed almost no change in PLC level, and a minor accumulation of transketolase, phycoerythrocyanin alpha-chain and both isoforms of SOD after 7 and recovery after 10 days. Acclimated strain under excess Cu, however, exhibited significant accumulation of both isoforms of SOD, plastocyanin, phosphoribulokinase and transketolase, which seem to counteract oxidative damage, serve as an alternate electron carrier from cytochrome b6/f complex to photosystem I and meet the NADPH and ATP requirements, respectively, under anoxygenic photosynthesis. In view of the kinetics of the hypothetical protein alr0803 (no change in expression level for 7, maximum after 10 and decline after 15 days) its involvement in metal homeostasis is suggested.

In vivo-folded metal-metallothionein 3 complexes reveal the Cu-thionein rather than Zn-thionein character of this brain-specific mammalian metallothionein.

PubMed

Artells, Ester; Palacios, Oscar; Capdevila, Mercè; Atrian, Sílvia

2014-03-01

Metallothionein-3 (MT3) is one of the four mammalian metallothioneins (MT), and is constitutively synthesized in the brain. MT3 acts both intracellularly and extracellularly in this organ, performing functions related to neuronal growth and physiological metal (Zn and Cu) handling. It appears to be involved in the prevention of neurodegenerative disorders caused by insoluble Cu-peptide aggregates, as it triggers a Zn-Cu swap that may counteract the deleterious presence of copper in neural tissues. The literature data on MT3 coordination come from studies either on apo-MT3 reconstitution or the reaction of Zn-MT3 with Cu(2+) , an ion that is hardly present inside cells. To ascertain the MT3 metal-binding features in a scenario closer to the reductive cell cytoplasm, a study of the recombinant Zn(2+) , Cd(2+) and Cu(+) complexes of MT3, βMT3, and αMT3, as well as the in vitro Zn(2+) -Cd(2+) and Zn(2+) -Cu(+) replacement processes, is presented here. We conclude that MT3 has a Cu-thionein character that is stronger than that of the MT1 and MT2 isoforms - also present in the mammalian brain - which is mainly contributed by its β domain. In contrast, the α domain retains a high capacity to bind Zn(2+) ions, and, consequently, the entire MT3 peptide shows a peculiar dual ability to handle both metal ions. The nature of the formed Cu(+) -MT3 complexes oscillates from heterometallic Cu6 Zn4 -MT3 to homometallic Cu10 -MT3 major species, in a narrow Cu concentration range. Therefore, the entire MT3 peptide shows a high capacity to bind Cu(+) , provided that this occurs in a nonoxidative milieux. This reflects a peculiar property of this MT isoform, which accurately senses different Cu contents in the environment in which it is synthesized. © 2014 FEBS.

Direct ROS scavenging activity of CueP from Salmonella enterica serovar Typhimurium.

PubMed

Yoon, Bo-Young; Yeom, Ji-Hyun; Kim, Jin-Sik; Um, Si-Hyeon; Jo, Inseong; Lee, Kangseok; Kim, Yong-Hak; Ha, Nam-Chul

2014-02-01

Salmonella enterica serovar Typhimurium (S. Typhimurium) is an intracellular pathogen that has evolved to survive in the phagosome of macrophages. The periplasmic copper-binding protein CueP was initially known to confer copper resistance to S. Typhimurium. Crystal structure and biochemical studies on CueP revealed a putative copper binding site surrounded by the conserved cysteine and histidine residues. A recent study reported that CueP supplies copper ions to periplasmic Cu, Zn-superoxide dismutase (SodCII) at a low copper concentration and thus enables the sustained SodCII activity in the periplasm. In this study, we investigated the role of CueP in copper resistance at a high copper concentration. We observed that the survival of a cueP-deleted strain of Salmonella in macrophage phagosome was significantly reduced. Subsequent biochemical experiments revealed that CueP specifically mediates the reduction of copper ion using electrons released during the formation of the disulfide bond. We observed that the copper ion-mediated Fenton reaction in the presence of hydrogen peroxide was blocked by CueP. This study provides insight into how CueP confers copper resistance to S. Typhimurium in copper-rich environments such as the phagosome of macrophages.

Influence of cadmium on antioxidant capacity and four microelement concentrations in tomato seedlings (Lycopersicon esculentum).

PubMed

Dong, Jing; Wu, Feibo; Zhang, Guoping

2006-09-01

Tomato (Lycopersicon esculentum) seedlings were grown in four cadmium (Cd) levels of 0-10 microM in a hydroponic system to analyze the antioxidative enzymes, Cd concentration in the plants, and the interaction between Cd and four microelements. The results showed that there was a significant increase in malondialdehyde (MDA) concentration, and superoxide dismutase (SOD) and peroxidase (POD) activities in the plants subjected to 1-10 microM Cd. This indicates that Cd stress induces an oxidative stress response in tomato plants, characterized by an accumulation of MDA and increase in activities of SOD and POD. Root, stem and leaf Cd concentrations increased with its exposure Cd level, and the highest Cd concentration occurred in roots, followed by leaves and stems. A concentration- and tissue-dependent response was found in the four microelement concentrations to Cd stress in the tomato leaves, stems and roots. Regression analysis showed that there was a significantly negative correlation between Cd and Mn, implying the antagonistic effect of Cd on Mn absorption and translocation. The correlation between Cd and Zn, Cu and Fe were inconsistent among leaves, stems and roots.

Effect of the French Oak Wood Extract Robuvit on Markers of Oxidative Stress and Activity of Antioxidant Enzymes in Healthy Volunteers: A Pilot Study

PubMed Central

Orszaghova, Zuzana; Laubertova, Lucia; Sabaka, Peter; Rohdewald, Peter; Durackova, Zdenka; Muchova, Jana

2014-01-01

We examined in vitro antioxidant capacity of polyphenolic extract obtained from the wood of oak Quercus robur (QR), Robuvit, using TEAC (Trolox equivalent antioxidant capacity) method and the effect of its intake on markers of oxidative stress, activity of antioxidant enzymes, and total antioxidant capacity in plasma of 20 healthy volunteers. Markers of oxidative damage to proteins, DNA, and lipids and activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the erythrocytes. We have found an in vitro antioxidant capacity of Robuvit of 6.37 micromole Trolox equivalent/mg of Robuvit. One month intake of Robuvit in daily dose of 300 mg has significantly decreased the serum level of advanced oxidation protein products (AOPP) and lipid peroxides (LP). Significantly increased activities of SOD and CAT as well as total antioxidant capacity of plasma after one month intake of Robuvit have been shown. In conclusion, we have demonstrated for the first time that the intake of Robuvit is associated with decrease of markers of oxidative stress and increase of activity of antioxidant enzymes and total antioxidant capacity of plasma in vivo. PMID:25254080

A full-spectrum photocatalyst with strong near-infrared photoactivity derived from synergy of nano-heterostructured Er3+-doped multi-phase oxides.

PubMed

Chen, Huabin; Liu, Wenxia; Hu, Bin; Qin, Zhuozhuo; Liu, Hong

2017-12-07

The development of full-spectrum photocatalysts active in the near-infrared (NIR) region has gained increasing attention in the photodegradation of organic pollutants. Herein, we designed a full-spectrum photocatalyst with strong NIR photoactivity based on the synergy of Er 3+ -doped ZnO-CuO-ZnAl 2 O 4 multi-phase oxides (Er 3+ -doped Zn/Cu/Al-MPO) via the formation of n-p-n double heterojunctions. The photocatalyst was prepared by synthesizing nanosheets of a Zn/Cu/Al/Er hydrotalcite-like compound (Zn/Cu/Al/Er-HLC) with a co-precipitation method followed by calcination of the nanosheets at 800 °C. The as-prepared Er 3+ -doped Zn/Cu/Al-MPO inherits the nanosheet morphology of Zn/Cu/Al/Er-HLC, and displays over-doubled photoactivity in the entire ultraviolet (UV), visible and NIR regions compared to undoped Zn/Cu/Al-MPO. The excellent photocatalytic activity of Er 3+ -doped Zn/Cu/Al-MPO, especially its strong NIR photoactivity, is ascribed to its Er 3+ -doped CuO-involved multi-crystalline phase heterostructure, i.e., n-p-n double heterojunctions, which does not only offer an enhanced NIR absorption but also promotes the separation of photogenerated charge carriers. Importantly, the synergy of all the parts of the n-p-n double heterojuctions plays an important role in interface band structure regulation for the enhancement of the photocatalytic properties of Er 3+ -doped Zn/Cu/Al-MPO. This work has demonstrated the feasibility of utilizing hydrotalcite-like precursors in the design of full-spectrum photocatalysts active in the NIR region.

Zinc and copper behaviour at the soil-river interface: New insights by Zn and Cu isotopes in the organic-rich Rio Negro basin

NASA Astrophysics Data System (ADS)

Guinoiseau, Damien; Gélabert, Alexandre; Allard, Thierry; Louvat, Pascale; Moreira-Turcq, Patricia; Benedetti, Marc F.

2017-09-01

The complex behaviour of Zn and Cu at the soil-river interface was investigated in soil and riverine water samples from the Rio Negro basin, a secondary tributary of the Rio Amazonas, using their stable isotope compositions. This acidic and organic river drains two types of intensely weathered terrains: podzols in its upstream part, and lateritic soils downstream. Bulk soil particles, suspended particulate matter (SPM) as well as colloidal fractions were sampled across the whole basin during low and high water stages. In the basin, Zn and Cu are mostly exported from lateritic soils and transported by organic colloids where significant losses are observed in the downstream part of the river. The use of δ66Zn and δ65Cu measurements reveals distinct stories for these two metals in suspended sediments and colloids. In the colloids, the constant δ66Zncoll across the basin is induced by the same weak association mode between Zn and organic ligands, regardless of the origin of the water. By contrast, in SPM, the speciation of Zn and thus δ66ZnSPM differ according to the type of drained soils. Zn is associated with organic complexes in particles exported with water draining podzol whereas Zn2+ is incorporated in the structure of the remaining kaolinite clays in lateritic output. The stronger reactivity of Cu than Zn with organic ligands induces its complete complexation. Copper is controlled by refractory particulate organic matter (POM) and by reactive colloidal organic matter; the latter being enriched in 65Cu due to stronger binding interactions than in POM. While the Cu content remains constant in the upstream part of the Rio Negro, downstream, the decrease of SPM and colloidal Cu fluxes is associated with a constant δ65CuSPM and with an increase of δ65Cucoll at the Rio Negro outlet. Geochemical mass balance modelling, based on SPM, Cu and Zn fluxes in SPM and their associated isotopic signatures, confirms distinct host phases for Zn and Cu, and identifies the most probable places where losses of these two metals occur. In colloids, the observed Cu isotope fractionation (from 0.24 to 0.45‰) superimposed on the significant Cucoll loss is assumed to result from a new isotopic equilibrium in a low velocity and high productivity zone: Cu-rich colloids enriched in 63Cu aggregate and settle down, whereas the remaining heavy Cu is partially complexed on strong organic ligands secreted by phytoplankton, forming new Cu-colloids.

Characterization of free radical defense system in high glucose cultured HeLa-tat cells: consequences for glucose-induced cytotoxicity.

PubMed

Bouvard, Sophie; Faure, Patrice; Roucard, Corinne; Favier, Alain; Halimi, Serge

2002-09-01

HeLa cell line stably transfected with the tat gene from human immunodeficiency virus type 1 has a decreased antioxidant potential. In this work, we used this model to investigate the effect of a high glucose level (20 mM) on the glucose induced cytotoxicity and on the antioxidant system. In comparison to cell culture under control medium, HeLa-wild cell cultured under 20 mM glucose did not exhibit necrosis or apoptosis, contrary to HeLa-tat cell presenting a significant increase in necrotic or apoptotic state. Moreover after 48 h culture under high glucose level the HeLa-tat proliferation rate was not higher than the one of HeLa-wild cells. In HeLa-wild cell high glucose level resulted in an induction of glutathione reductase activity in opposition to HeLa-tat cells where no change was observed. High glucose level resulted in 20% increase in GSSG/GSH ratio in HeLa-wild cells and 38% increase in HeLa-tat cells. Moreover, high glucose level resulted in a dramatic cytosolic thiol decrease and an important lipid peroxidation in HeLa-tat cells. No significant change of these two parameters was observed in HeLa-wild cells. In both cell lines, high glucose resulted in an increase of total SOD activity, as a consequence of the increase in Cu,Zn-SOD activity. High glucose did not result in an increase of Mn-SOD activity in both cell lines. As a consequence of tat tranfection Mn-SOD activity was 50% lower in HeLa-tat cells in comparison to HeLa-wild cells. This work emphasizes the importance of the antioxidant system in the glucose induced cytotoxicity.

Expression and Distribution of Arylsulfatase B are Closely Associated with Neuron Death in SOD1 G93A Transgenic Mice.

PubMed

Zhang, Jie; Liang, Huiting; Zhu, Lei; Gan, Weiming; Tang, Chunyan; Li, Jiao; Xu, Renshi

2018-02-01

The known proteins only explained the partial pathogenesis of amyotrophic lateral sclerosis (ALS). Therefore, this study aimed to search the novel proteins possibly involved in ALS. In this study, we analyzed the expression and distribution of the candidate protein arylsulfatase B (ARSB) in the different segments, anatomic regions, and neural cells of spinal cord at the different stages of the wild-type and [Cu/Zn] superoxide dismutase 1 (SOD1) G93A transgenic mice using the fluorescent immunohistochemistry and the western blot. The results revealed that the ARSB was extensively expressed and distributed in the entire spinal cord; the expression and distribution of ARSB was significantly different in the different regions of spinal cord, the anterior horn of gray matter (AHGM) was significantly more than that in the posterior horn of gray matter (PHGM) and significantly more than that in the central canal, and ARSB was mainly distributed in the microglia and neuron cells in the wild-type mice. The expression of ARSB significantly increased in other anatomic regions besides the thoracic PHGM, significantly decreased at the progression stage, occurred in the redistribution from the AHGM and the PHGM to the central canal at the onset and progression stages, and no any alteration of ARSB expression and distribution occurred between the different neural cells in the SOD1 G93A mice compared with the wild-type mice. The increase of ARSB expression and distribution followed with the increased of neuron death. Our data suggested that the abnormal expression and distribution of ARSB were closely associated with the neuron death in the SOD1 G93A transgenic mice.

Superoxide Dismutase Mimetic GC4419 Enhances the Oxidation of Pharmacological Ascorbate and Its Anticancer Effects in an H₂O₂-Dependent Manner.

PubMed

Heer, Collin D; Davis, Andrew B; Riffe, David B; Wagner, Brett A; Falls, Kelly C; Allen, Bryan G; Buettner, Garry R; Beardsley, Robert A; Riley, Dennis P; Spitz, Douglas R

2018-01-19

Lung cancer, together with head and neck cancer, accounts for more than one-fourth of cancer deaths worldwide. New, non-toxic therapeutic approaches are needed. High-dose IV vitamin C (aka, pharmacological ascorbate; P-AscH - ) represents a promising adjuvant to radiochemotherapy that exerts its anti-cancer effects via metal-catalyzed oxidation to form H₂O₂. Mn(III)-porphyrins possessing superoxide dismutase (SOD) mimetic activity have been shown to increase the rate of oxidation of AscH - , enhancing the anti-tumor effects of AscH - in several cancer types. The current study demonstrates that the Mn(II)-containing pentaazamacrocyclic selective SOD mimetic GC4419 may serve as an AscH - /O₂ •- oxidoreductase as evidenced by the increased rate of oxygen consumption, steady-state concentrations of ascorbate radical, and H₂O₂ production in complete cell culture media. GC4419, but not CuZnSOD, was shown to significantly enhance the toxicity of AscH - in H1299, SCC25, SQ20B, and Cal27 cancer cell lines. This enhanced cancer cell killing was dependent upon the catalytic activity of the SOD mimetic and the generation of H₂O₂, as determined using conditional overexpression of catalase in H1299T cells. GC4419 combined with AscH - was also capable of enhancing radiation-induced cancer cell killing. Currently, AscH - and GC4419 are each being tested separately in clinical trials in combination with radiation therapy. Data presented here support the hypothesis that the combination of GC4419 and AscH - may provide an effective means by which to further enhance radiation therapy responses.

Subacute exposure to N-ethyl perfluorooctanesulfonamidoethanol results in the formation of perfluorooctanesulfonate and alters superoxide dismutase activity in female rats.

PubMed

Xie, Wei; Wu, Qian; Kania-Korwel, Izabela; Tharappel, Job C; Telu, Sanjay; Coleman, Mitchell C; Glauert, Howard P; Kannan, Kurunthachalam; Mariappan, S V S; Spitz, Douglas R; Weydert, Jamie; Lehmler, Hans-Joachim

2009-10-01

Perfluorooctanesulfonamides, such as N-ethyl perfluorooctanesulfonamidoethanol (N-EtFOSE), are large scale industrial chemicals but their disposition and toxicity are poorly understood despite significant human exposure. The hypothesis that subacute exposure to N-EtFOSE, a weak peroxisome proliferator, causes a redox imbalance in vivo was tested using the known peroxisome proliferator, ciprofibrate, as a positive control. Female Sprague-Dawley rats were treated orally with N-EtFOSE, ciprofibrate or corn oil (vehicle) for 21 days, and levels of N-EtFOSE and its metabolites as well as markers of peroxisome proliferation and oxidative stress were assessed in serum, liver and/or uterus. The N-EtFOSE metabolite profile in liver and serum was in good agreement with reported in vitro biotransformation pathways in rats and the metabolite levels decreasing in the order perfluorooctanesulfonate > perfluorooctanesulfonamide ~ N-ethyl perfluorooctanesulfonamidoacetate > perfluorooctanesulfonamidoethanol approximately N-EtFOSE. Although N-EtFOSE treatment significantly decreased the growth rate, increased relative liver weight and activity of superoxide dismutases (SOD) in liver and uterus (total SOD, CuZnSOD and MnSOD), a metabolic study revealed no differences in the metabolome in serum from N-EtFOSE-treated and control animals. Ciprofibrate treatment increased liver weight and peroxisomal acyl Co-A oxidase activity in the liver and altered antioxidant enzyme activities in the uterus and liver. According to NMR metabolomic studies, ciprofibrate treated animals had altered serum lipid profiles compared to N-EtFOSE-treated and control animals, whereas putative markers of peroxisome proliferation in serum were not affected. Overall, this study demonstrates the biotransformation of N-EtFOSE to PFOS in rats that is accompanied by N-EtFOSE-induced alterations in antioxidant enzyme activity.

Hepatoprotective and Renoprotective Effects of Lavender (Lavandula stoechas L.) Essential Oils Against Malathion-Induced Oxidative Stress in Young Male Mice.

PubMed

Selmi, Slimen; Jallouli, Manel; Gharbi, Najoua; Marzouki, Lamjed

2015-10-01

We aimed in the present study to investigate the hepato- and nephroprotective effects of Lavandula stoechas essential oils (LSEO) against malathion-induced oxidative stress in young male mice as well as the possible mechanism implicated in such protection. Animals were divided into eight groups of 12 each: Control, malathion (200 mg/kg b.w.); Various doses of LSEO (10, 30, and 50 mg/kg b.w.), malathion+various doses of LSEO. Malathion and LSEO were daily per orally (p.o.) administered by intragastric gavage during 30 days. We initially found that malathion treatment induced body weight gain decrease as well as a clear nephro- and hepatotoxicity as assessed by significant relative liver and kidney weight increase and related hemodynamic parameters deregulation. Malathion exposure of mice also induced a considerable perturbation of metabolic parameters. On the other hand, we showed that malathion administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels as well as a depletion of sulfhydril group content (-SH) and antioxidant enzyme activities such as catalase (CAT) and glutathione peroxidase (GPx), total superoxide dismutase (SOD), Cu/Zn-SOD, Mn-SOD, and Fe-SOD in the kidney and liver. More importantly, LSEO treatment abolished all malathion-induced body gain loss, liver and kidney relative weight increase, hemodynamic and metabolic disorders, as well as hepatic and renal oxidative stress. In conclusion, our data suggest that LSEO exerted potential hepato- and nephroprotective effects against malathion-induced oxidative stress in mice. The beneficial effect of LSEO might be related, in part, to its antioxidant properties.

Hepatoprotective and Renoprotective Effects of Lavender (Lavandula stoechas L.) Essential Oils Against Malathion-Induced Oxidative Stress in Young Male Mice

PubMed Central

Jallouli, Manel; Gharbi, Najoua; Marzouki, Lamjed

2015-01-01

Abstract We aimed in the present study to investigate the hepato- and nephroprotective effects of Lavandula stoechas essential oils (LSEO) against malathion-induced oxidative stress in young male mice as well as the possible mechanism implicated in such protection. Animals were divided into eight groups of 12 each: Control, malathion (200 mg/kg b.w.); Various doses of LSEO (10, 30, and 50 mg/kg b.w.), malathion+various doses of LSEO. Malathion and LSEO were daily per orally (p.o.) administered by intragastric gavage during 30 days. We initially found that malathion treatment induced body weight gain decrease as well as a clear nephro- and hepatotoxicity as assessed by significant relative liver and kidney weight increase and related hemodynamic parameters deregulation. Malathion exposure of mice also induced a considerable perturbation of metabolic parameters. On the other hand, we showed that malathion administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels as well as a depletion of sulfhydril group content (-SH) and antioxidant enzyme activities such as catalase (CAT) and glutathione peroxidase (GPx), total superoxide dismutase (SOD), Cu/Zn-SOD, Mn-SOD, and Fe-SOD in the kidney and liver. More importantly, LSEO treatment abolished all malathion-induced body gain loss, liver and kidney relative weight increase, hemodynamic and metabolic disorders, as well as hepatic and renal oxidative stress. In conclusion, our data suggest that LSEO exerted potential hepato- and nephroprotective effects against malathion-induced oxidative stress in mice. The beneficial effect of LSEO might be related, in part, to its antioxidant properties. PMID:25835641

Subacute Exposure to N-Ethyl Perfluorooctanesulfonamidoethanol Results in the Formation of Perfluorooctanesulfonate and Alters Superoxide Dismutase Activity in Female Rats

PubMed Central

Xie, Wei; Wu, Qian; Kania-Korwel, Izabela; Tharappel, Job C.; Telu, Sanjay; Coleman, Mitchell C.; Glauert, Howard P.; Kannan, Kurunthachalam; Santhana Mariappan, S. V.; Spitz, Douglas R.; Weydert, Jamie; Lehmler, Hans-Joachim

2009-01-01

Perfluorooctanesulfonamides, such as N-ethyl perfluorooctanesulfonamidoethanol (N-EtFOSE), are large scale industrial chemicals but their disposition and toxicity are poorly understood despite significant human exposure. The hypothesis that subacute exposure to N-EtFOSE, a weak peroxisome proliferator, causes a redox imbalance in vivo was tested using the known peroxisome proliferator, ciprofibrate, as a positive control. Female Sprague-Dawley rats were treated orally with N-EtFOSE, ciprofibrate or corn oil (vehicle) for 21 days, and levels of N-EtFOSE and its metabolites as well as markers of peroxisome proliferation and oxidative stress were assessed in serum, liver and/or uterus. The N-EtFOSE metabolite profile in liver and serum was in good agreement with reported in vitro biotransformation pathways in rats and the metabolite levels decreasing in the order perfluorooctanesulfonate ≫ perfluorooctanesulfonamide ∼ N-ethyl perfluorooctanesulfonamidoacetate ≫ perfluorooctanesulfonamidoethanol ∼ N-EtFOSE. Although N-EtFOSE treatment significantly decreased the growth rate, increased relative liver weight and activity of superoxide dismutases (SOD) in liver and uterus (total SOD, CuZnSOD and MnSOD), a metabolic study revealed no differences in the metabolome in serum from N-EtFOSE-treated and control animals. Ciprofibrate treatment increased liver weight and peroxisomal acyl Co-A oxidase activity in the liver and altered antioxidant enzyme activities in the uterus and liver. According to NMR metabolomic studies, ciprofibrate treated animals had altered serum lipid profiles compared to N-EtFOSE-treated and control animals, whereas putative markers of peroxisome proliferation in serum were not affected. Overall, this study demonstrates the biotransformation of N-EtFOSE to PFOS in rats that is accompanied by N-EtFOSE-induced alterations in antioxidant enzyme activity. PMID:19544052

Oxidative stress induction by Prunus necrotic ringspot virus infection in apricot seeds.

PubMed

Amari, Khalid; Díaz-Vivancos, Pedro; Pallás, Vincente; Sánchez-Pina, María Amelia; Hernández, José Antonio

2007-10-01

Prunus necrotic ringspot rvirus (PNRSV) was able to invade the immature apricot seed including the embryo. The amount of virus was very high inside the embryo compared with that present in the cotyledons. PNRSV infection produced an oxidative stress in apricot seeds as indicated by the increase in lipid peroxidation, measured as thiobarbituric acid-reactive substances. This lipid peroxidation increase was parallelled with an imbalance in the seed antioxidant enzymes. A significant decrease in the ascorbate-GSH cycle enzymes as well as in peroxidase (POX) activity took place in infected seeds, suggesting a low capability to eliminate H2O2. No changes in superoxide dismutase (SOD) or catalase activity were observed. A significant decrease in polyphenoloxidase (PPO) activity was also observed. Native PAGE revealed the presence of three different SOD activity bands in apricot seeds: a Mn-containing SOD and two CuZn-containing SODs. Only an isozyme with catalase, glutathione reductase (GR) or PPO activity was detected in both healthy and infected apricot seeds. Regarding POX staining, three bands with POX activity were detected in native gels in both healthy and infected seeds. The gel results emphasise that the drop detected in POX, GR and PPO activities in PNRSV-infected apricot seeds by kinetic analyses was also evident from the results obtained by native PAGE. The oxidative stress and the imbalance in the antioxidant systems from PNRSV-infected apricot seeds resemble the hypersensitive response observed in some virus-host interactions. This defence mechanism would inactivate PNRSV during seed formation and/or the storage period or even during seed germination. Those results can explain the decrease in seed germination and the low transmission of PNRSV by seeds in apricot trees.

Cu0-loaded SBA-15@ZnO with improved electrical properties and affinity towards hydrogen

NASA Astrophysics Data System (ADS)

Bouazizi, N.; Louhichi, S.; Ouargli, R.; Bargougui, R.; Vieillard, J.; Derf, F. Le; Azzouz, A.

2017-05-01

A core-shell material was prepared using SBA-15 crystallites as cores for the growth of a ZnO shell, followed by Cu0 dispersion. The resulting Cu/SBA-15@ZnO nanostructure displayed higher specific surface area (SSA) and higher number of smaller pores as compared to the starting materials. Dispersion of fine Cu0NPs induced a compaction of the host matrice and a marked decay of the hydrophilic character, explained in terms of the involvement of terminal hydroxyl groups in competitive sbnd HO:Cu interaction at the expense of H-bridges with water. Heating at 400-450 °C seems to trigger ZnO dehydroxylation with possible self-polycondensation and/or the formation of Si-O-Zn bridges. This is an additional explanation of the significant SSA increase and decrease in the average pore diameter. Both ZnO and Cu0NP incorporation induced shifts in the UV-vis absorption band towards higher wavelengths, indicating a decrease in the optical band gap energy and an improvement of the conductance properties. As compared to ZnO, Cu0NPs produced stronger improvement of the conductance, which was found to increase with higher frequencies. Cu/SBA-15@ZnO also displayed higher affinity towards hydrogen as compared to SBA-15@ZnO and SBA-15 at ambient conditions. These outstanding properties combined to an appreciable thermal stability are worth to be prone to deeper investigations, because they can open promising prospects for Cu/SBA-15@ZnO as sensor, electrode material, electrocatalyst and/or hydrogen capture matrice.

Growth of Cu2ZnSnSe4 Film under Controllable Se Vapor Composition and Impact of Low Cu Content on Solar Cell Efficiency.

PubMed

Li, Jianjun; Wang, Hongxia; Wu, Li; Chen, Cheng; Zhou, Zhiqiang; Liu, Fangfang; Sun, Yun; Han, Junbo; Zhang, Yi

2016-04-27

It is a challenge to fabricate high quality Cu2ZnSnSe4 (CZTSe) film with low Cu content (Cu/(Zn + Sn) < 0.8). In this work, the growth mechanisms of CZTSe films under different Se vapor composition are investigated by DC-sputtering and a postselenization approach. The composition of Se vapor has important influence on the compactability of the films and the diffusion of elements in the CZTSe films. By adjusting the composition of Se vapor during the selenization process, an optimized two step selenization process is proposed and highly crystallized CZTSe film with low Cu content (Cu/(Zn + Sn) = 0.75) is obtained. Further study of the effect of Cu content on the morphology and photovoltaic performance of the corresponding CZTSe solar cells has shown that the roughness of the CZTSe absorber film increases when Cu content decreases. As a consequence, the reflection loss of CZTSe solar cells reduces dramatically and the short circuit current density of the cells improve from 34.7 mA/cm(2) for Cu/(Zn + Sn) = 0.88 to 38.5 mA/cm(2) for Cu/(Zn + Sn) = 0.75. In addition, the CZTSe solar cells with low Cu content show longer minority carrier lifetime and higher open circuit voltage than the high Cu content devices. A champion performance CZTSe solar cell with 10.4% efficiency is fabricated with Cu/(Zn + Sn) = 0.75 in the CZTSe film without antireflection coating.

Rapid, controllable, one-pot and room-temperature aqueous synthesis of ZnO:Cu nanoparticles by pulsed UV laser and its application for photocatalytic degradation of methyl orange.

PubMed

Arabi, Mozhgan; Baizaee, Seyyed Mahdy; Bahador, Alireza; Otaqsara, Seyed Mohammad Taheri

2018-05-01

Zinc oxide (ZnO) and ZnO:Cu nanoparticles (NPs) were synthesized using a rapid, controllable, one-pot and room-temperature pulsed UV-laser assisted method. UV-laser irradiation was used as an effective energy source in order to gain better control over the NPs size and morphology in aqueous media. Parameters effective in laser assisted synthesis of NPs such as irradiation time and laser shot repetition rate were optimized. Photoluminescence (PL) spectra of ZnO NPs showed a broad emission with two trap state peaks located at 442 and 485 nm related to electronic transition from zinc interstitial level (I Zn ) to zinc vacancy level (V Zn ) and electronic transition from conduction band to the oxygen vacancy level (V O ), respectively. For ZnO:Cu NPs, trap state emissions disappeared completely and a copper (Cu)-related emission appeared. PL intensity of Cu-related emission increased with the increase in concentration of Cu 2+ , so that for molar ratio of Cu:Zn 2%, optimal value of PL intensity was obtained. The photocatalytic activity of Cu-doped ZnO revealed 50 and 100% increasement than that of undoped NPs under UV and visible irradiation, respectively. The enhanced photocatalytic activity could be attributed to smaller crystal size, as well as creation of impurity acceptor levels (T 2 ) inside the ZnO energy band gap. Copyright © 2017 John Wiley & Sons, Ltd.

Nanosized CuO and ZnO catalyst supported on titanium chip for conversion of carbon dioxide to methyl alcohol.

PubMed

Seo, Hyeong-Seok; Park, Chul-Min; Kim, Ki-Joong; Jeong, Woon-Jo; Chung, Min-Chul; Jung, Sang-Chul; Kim, Sang-Chai; Ahn, Ho-Geun

2013-08-01

In order to reutilize spent metallic titanium chips (TC) as catalyst support or photocatalytic materials, the surface of the TC was modified by thermal treatment under air atmosphere. TC-supported nanosized CuO and ZnO catalysts were prepared by impregnation (IMP) and co-precipitation (CP) method, respectively. The catalytic activity for CO2 hydrogenation to CH3OH was investigated using a flow-typed reactor under various reaction pressures. The crystals of CuO and ZnO was well formed on TC. CO2 conversion, CH3OH selectivity, and CH3OH yield were obtained as a function of time on stream over CuO-ZnO/TC catalysts. Conversion of CO2 to CH3OH over CuO-ZnO/TC catalyst by CP method and CuO/ZnO/TC catalyst by IMP method were ca. 16% and ca. 12%, respectively. Conversion of CO2 over CuO-ZnO/TC catalyst by CP method was increased with increasing reaction temperature in the range of 15-30 atm. Maximum selectivity and yield to CH3OH over CuO-ZnO/TC at 250 degrees C were ca. 90% at 20 atm and ca. 18.2% at 30 atm, respectively.

Ultrasensitive non-enzymatic glucose sensor based on three-dimensional network of ZnO-CuO hierarchical nanocomposites by electrospinning

PubMed Central

Zhou, Chunyang; Xu, Lin; Song, Jian; Xing, Ruiqing; Xu, Sai; Liu, Dali; Song, Hongwei

2014-01-01

Three-dimensional (3D) porous ZnO–CuO hierarchical nanocomposites (HNCs) nonenzymatic glucose electrodes with different thicknesses were fabricated by coelectrospinning and compared with 3D mixed ZnO/CuO nanowires (NWs) and pure CuO NWs electrodes. The structural characterization revealed that the ZnO–CuO HNCs were composed of the ZnO and CuO mixed NWs trunk (~200 nm), whose outer surface was attached with small CuO nanoparticles (NPs). Moreover, a good synergetic effect between CuO and ZnO was confirmed. The nonenzymatic biosensing properties of as prepared 3D porous electrodes based on fluorine doped tin oxide (FTO) were studied and the results indicated that the sensing properties of 3D porous ZnO–CuO HNCs electrodes were significantly improved and depended strongly on the thickness of the HNCs. At an applied potential of + 0.7 V, the optimum ZnO–CuO HNCs electrode presented a high sensitivity of 3066.4 μAmM−1cm−2, the linear range up to 1.6 mM, and low practical detection limit of 0.21 μM. It also showed outstanding long term stability, good reproducibility, excellent selectivity and accurate measurement in real serum sample. The formation of special hierarchical heterojunction and the well-constructed 3D structure were the main reasons for the enhanced nonenzymatic biosensing behavior. PMID:25488502

Electrical Study of Trapped Charges in Copper-Doped Zinc Oxide Films by Scanning Probe Microscopy for Nonvolatile Memory Applications

PubMed Central

Su, Ting; Zhang, Haifeng

2017-01-01

Charge trapping properties of electrons and holes in copper-doped zinc oxide (ZnO:Cu) films have been studied by scanning probe microscopy. We investigated the surface potential dependence on the voltage and duration applied to the copper-doped ZnO films by Kelvin probe force microscopy. It is found that the Fermi Level of the 8 at.% Cu-doped ZnO films shifted by 0.53 eV comparing to undoped ZnO films. This shift indicates significant change in the electronic structure and energy balance in Cu-doped ZnO films. The Fermi Level (work function) of zinc oxide films can be tuned by Cu doping, which are important for developing this functional material. In addition, Kelvin probe force microscopy measurements demonstrate that the nature of contact at Pt-coated tip/ZnO:Cu interface is changed from Schottky contact to Ohmic contact by increasing sufficient amount of Cu ions. The charge trapping property of the ZnO films enhance greatly by Cu doping (~10 at.%). The improved stable bipolar charge trapping properties indicate that copper-doped ZnO films are promising for nonvolatile memory applications. PMID:28135335

The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice.

PubMed

Kojima, Takashi; Dogru, Murat; Ibrahim, Osama M; Nagata, Taeko; Higa, Kazunari; Shimizu, Takahiko; Shirasawa, Takuji; Satake, Yoshiyuki; Shimazaki, Seika; Shimazaki, Jun; Tsubota, Kazuo

2014-01-01

To investigate the role of a water and mucin secretagogue (3% diquafosol sodium eye drops) on the tear function and conjunctival ocular surface changes in Sod1(-/-) in comparison to the wild-type (WT) mice. Fourteen eyes of 7 Sod1(-/-) male mice with C57BL/background and 14 eyes of 7 C57BL6 strain wild-type male mice were examined at 40 weeks in this study. All mice had application of 3% diquafosol ophthalmic solution six times a day for 2 weeks. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was performed before and after eye drop instillations. Aqueous tear quantity was measured with phenol red-impregnated cotton threads without anesthesia. Animals were sacrificed at 42 weeks after diquafosol treatment and the whole globe specimens were subjected to periodic acid Schiff staining. Goblet cell density was quantified by J Image software. Quantitative real-time PCR for conjunctival muc 5AC messenger RNA expression was also performed. Sod1(-/-) mice had significantly higher fluorescein staining scores compared to the WT mice before eye drop instillation. The mean tear film breakup time, Rose Bengal staining scores, and muc5 messenger RNA expression improved significantly with diquafosol treatment in both the WT and the knockout mice. The mean fluorescein staining score and aqueous tear quantity significantly improved in the Sod1(-/-) mice with treatment. A notable and consistent increase in goblet cells and decrease in inflammatory cell infiltrates could be confirmed in all specimens after 2 weeks of diquafosol eye drop application. Three percent diquafosol ophthalmic solution appears to be effective in the treatment of ocular surface disease in this age-related dry eye disease mouse model.

Study on room temperature gas-sensing performance of CuO film-decorated ordered porous ZnO composite by In2O3 sensitization

NASA Astrophysics Data System (ADS)

Li, Tian-tian; Bao, Na; Geng, Ai-fang; Yu, Hui; Yang, Ying; Dong, Xiang-ting

2018-02-01

For the first time, ordered mesoporous ZnO nanoparticles have been synthesized by a template method. The electroplating after chemical plating method was creatively used to form copper film on the surface of the prepared ZnO, and then a CuO film-decorated ordered porous ZnO composite (CuO/ZnO) was obtained by a high-temperature oxidation method. In2O3 was loaded into the prepared CuO film-ZnO by an ultrasonic-assisted method to sensitize the room temperature gas-sensing performance of the prepared CuO/ZnO materials. The doped In2O3 could effectively improve the gas-sensing properties of the prepared materials to nitrogen oxides (NOx) at room temperature. The 1% In2O3 doped CuO/ZnO sample (1 wt% In2O3-CuO/ZnO) showed the best gas-sensing properties whose response to 100 ppm NOx reached 82%, and the detectable minimum concentration reached 1 ppm at room temperature. The prepared materials had a good selectivity, better response, very low detection limit, and high sensitivity to NOx gas at room temperature, which would have a great development space in the gas sensor field and a great research value.

Magnetically engineered Cd-free quantum dots as dual-modality probes for fluorescence/magnetic resonance imaging of tumors.

PubMed

Ding, Ke; Jing, Lihong; Liu, Chunyan; Hou, Yi; Gao, Mingyuan

2014-02-01

Magnetically engineered Cd-free CuInS2@ZnS:Mn quantum dots (QDs) were designed, synthesized, and evaluated as potential dual-modality probes for fluorescence and magnetic resonance imaging (MRI) of tumors in vivo. The synthesis of Mn-doped core-shell structured CuInS2@ZnS mainly comprised three steps, i.e., the preparation of fluorescent CuInS2 seeds, the particle surface coating of ZnS, and the Mn-doping of the ZnS shells. Systematic spectroscopy studies were carried out to illustrate the impacts of ZnS coating and the following Mn-doping on the optical properties of the QDs. In combination with conventional fluorescence, fluorescence excitation, and time-resolved fluorescence measurements, the structure of CuInS2@ZnS:Mn QDs prepared under optimized conditions presented a Zn gradient CuInS2 core and a ZnS outer shell, while Mn ions were mainly located in the ZnS shell, which well balanced the optical and magnetic properties of the resultant QDs. For the following in vivo imaging experiments, the hydrophobic CuInS2@ZnS:Mn QDs were transferred into water upon ligand exchange reactions by replacing the 1-dodecanethiol ligand with dihydrolipoic acid-poly(ethylene glycol) (DHLA-PEG) ligand. The MTT assays based on HeLa cells were carried out to evaluate the cytotoxicity of the current Cd-free CuInS2@ZnS:Mn QDs for comparing with that of water soluble CdTe QDs. Further in vivo fluorescence and MR imaging experiments suggested that the PEGylated CuInS2@ZnS:Mn QDs could well target both subcutaneous and intraperitoneal tumors in vivo. Copyright © 2013 Elsevier Ltd. All rights reserved.

Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas

DOE PAGES

Hong-Hermesdorf, Anne; Miethke, Marcus; Gallaher, Sean D.; ...

2014-10-26

Here we identified a Cu-accumulating structure with a dynamic role in intracellular Cu homeostasis. During Zn limitation, Chlamydomonas reinhardtii hyperaccumulates Cu, a process dependent on the nutritional Cu sensor CRR1, but it is functionally Cu deficient. Visualization of intracellular Cu revealed major Cu accumulation sites coincident with electron-dense structures that stained positive for low pH and polyphosphate, suggesting that they are lysosome-related organelles. Nano-secondary ion MS showed colocalization of Ca and Cu, and X-ray absorption spectroscopy was consistent with Cu + accumulation in an ordered structure. Zn resupply restored Cu homeostasis concomitant with reduced abundance of these structures. Cu isotopemore » labeling demonstrated that sequestered Cu + became bioavailable for the synthesis of plastocyanin, and transcriptome profiling indicated that mobilized Cu became visible to CRR1. Cu trafficking to intracellular accumulation sites may be a strategy for preventing protein mismetallation during Zn deficiency and enabling efficient cuproprotein metallation or remetallation upon Zn resupply.« less

IR-Spectroscopic Study on the Interface of Cu-Based Methanol Synthesis Catalysts: Evidence for the Formation of a ZnO Overlayer

DOE PAGES

Schumann, Julia; Kröhnert, Jutta; Frei, Elias; ...

2017-08-28

Carbon monoxide was applied as probe molecule to compare the surface of a ZnO-containing (Cu/ZnO:Al) and a ZnO-free (Cu/MgO) methanol synthesis catalyst (copper content 70 atomic %) after reduction in hydrogen at 523 K by DRIFT spectroscopy. Nano-structured, mainly metallic copper was detected on the surface of the Cu/MgO catalyst. In contrast, the high energy of the main peak in the spectrum of CO adsorbed on reduced Cu/ZnO:Al (2125 cm -1) proves that metallic copper is largely absent on the surface of this catalyst. The band is assigned to Zn δ+–CO. The presence of not completely reduced Cu δ+–CO speciesmore » cannot be excluded. The results are interpreted in terms of a partial coverage of the copper nano-particles in the Cu/ZnO:Al catalyst by a thin layer of metastable, defective zinc oxide. Minor contributions in the spectrum at 2090 and 2112 cm -1 due to nano-structured Cu 0–CO and CO adsorbed on highly defective Cu 0, respectively, indicate that the coverage of metallic copper is not complete.« less

IR-Spectroscopic Study on the Interface of Cu-Based Methanol Synthesis Catalysts: Evidence for the Formation of a ZnO Overlayer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schumann, Julia; Kröhnert, Jutta; Frei, Elias

Carbon monoxide was applied as probe molecule to compare the surface of a ZnO-containing (Cu/ZnO:Al) and a ZnO-free (Cu/MgO) methanol synthesis catalyst (copper content 70 atomic %) after reduction in hydrogen at 523 K by DRIFT spectroscopy. Nano-structured, mainly metallic copper was detected on the surface of the Cu/MgO catalyst. In contrast, the high energy of the main peak in the spectrum of CO adsorbed on reduced Cu/ZnO:Al (2125 cm -1) proves that metallic copper is largely absent on the surface of this catalyst. The band is assigned to Zn δ+–CO. The presence of not completely reduced Cu δ+–CO speciesmore » cannot be excluded. The results are interpreted in terms of a partial coverage of the copper nano-particles in the Cu/ZnO:Al catalyst by a thin layer of metastable, defective zinc oxide. Minor contributions in the spectrum at 2090 and 2112 cm -1 due to nano-structured Cu 0–CO and CO adsorbed on highly defective Cu 0, respectively, indicate that the coverage of metallic copper is not complete.« less

Metal accumulation and oxidative stress biomarkers in octopus (Octopus vulgaris) from Northwest Atlantic.

PubMed

Semedo, Miguel; Reis-Henriques, Maria Armanda; Rey-Salgueiro, Ledicia; Oliveira, Marta; Delerue-Matos, Cristina; Morais, Simone; Ferreira, Marta

2012-09-01

Metals are ubiquitous in the environment and accumulate in aquatic organisms and are known for their ability to enhance the production of reactive oxygen species (ROS). In aquatic species, oxidative stress mechanisms have been studied by measuring antioxidant enzyme activities and oxidative damages in tissues. The aim of this study was to apply and validate a set of oxidative stress biomarkers and correlate responses with metal contents in tissues of common octopus (Octopus vulgaris). Antioxidant enzyme activity (catalase--CAT, superoxide dismutase--SOD and glutathione S-transferases--GST), oxidative damages (lipid peroxidation--LPO and protein carbonyl content--PCO) and metal content (Cu, Zn, Pb, Cd and As) in the digestive gland and arm of octopus, collected in the NW Portuguese coast in different periods, were assessed after capture and after 14 days in captivity. CAT and SOD activities were highly responsive to fluctuations in metal concentrations and able to reduce oxidative damage, LPO and PCO in the digestive gland. CAT activity was also positively correlated with SOD and GST activities, which emphasizes that the three enzymes respond in a coordinated way to metal induced oxidative stress. Our results validate the use of oxidative stress biomarkers to assess metal pollution effects in this ecological and commercial relevant species. Moreover, octopus seems to have the ability to control oxidative damage by triggering an antioxidant enzyme coordinated response in the digestive gland. Copyright © 2012 Elsevier B.V. All rights reserved.

Diverse fission yeast genes required for responding to oxidative and metal stress: Comparative analysis of glutathione-related and other defense gene deletions.

PubMed

Pluskal, Tomáš; Sajiki, Kenichi; Becker, Joanne; Takeda, Kojiro; Yanagida, Mitsuhiro

2016-06-01

Living organisms have evolved multiple sophisticated mechanisms to deal with reactive oxygen species. We constructed a collection of twelve single-gene deletion strains of the fission yeast Schizosaccharomyces pombe designed for the study of oxidative and heavy metal stress responses. This collection contains deletions of biosynthetic enzymes of glutathione (Δgcs1 and Δgsa1), phytochelatin (Δpcs2), ubiquinone (Δabc1) and ergothioneine (Δegt1), as well as catalase (Δctt1), thioredoxins (Δtrx1 and Δtrx2), Cu/Zn- and Mn- superoxide dismutases (SODs; Δsod1 and Δsod2), sulfiredoxin (Δsrx1) and sulfide-quinone oxidoreductase (Δhmt2). First, we employed metabolomic analysis to examine the mutants of the glutathione biosynthetic pathway. We found that ophthalmic acid was produced by the same enzymes as glutathione in S. pombe. The identical genetic background of the strains allowed us to assess the severity of the individual gene knockouts by treating the deletion strains with oxidative agents. Among other results, we found that glutathione deletion strains were not particularly sensitive to peroxide or superoxide, but highly sensitive to cadmium stress. Our results show the astonishing diversity in cellular adaptation mechanisms to various types of oxidative and metal stress and provide a useful tool for further research into stress responses. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Proteasomes remain intact, but show early focal alteration in their composition in a mouse model of amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Agar, Jeffrey N; Hong, Yu; Taylor, David M; Minotti, Sandra; Figlewicz, Denise A; Durham, Heather D

2008-06-01

In amyotrophic lateral sclerosis caused by mutations in Cu/Zn-superoxide dismutase (SOD1), altered solubility and aggregation of the mutant protein implicates failure of pathways for detecting and catabolizing misfolded proteins. Our previous studies demonstrated early reduction of proteasome-mediated proteolytic activity in lumbar spinal cord of SOD1(G93A) transgenic mice, tissue particularly vulnerable to disease. The purpose of this study was to identify any underlying abnormalities in proteasomal structure. In lumbar spinal cord of pre-symptomatic mice [postnatal day 45 (P45) and P75], normal levels of structural 20S alpha subunits were incorporated into 20S/26S proteasomes; however, proteasomal complexes separated by native gel electrophoresis showed decreased immunoreactivity with antibodies to beta3, a structural subunit of the 20S proteasome core, and beta5, the subunit with chymotrypsin-like activity. This occurred prior to increase in beta5i immunoproteasomal subunit. mRNA levels were maintained and no association of mutant SOD1 with proteasomes was identified, implicating post-transcriptional mechanisms. mRNAs also were maintained in laser captured motor neurons at a later stage of disease (P100) in which multiple 20S proteins are reduced relative to the surrounding neuropil. Increase in detergent-insoluble, ubiquitinated proteins at P75 provided further evidence of stress on mechanisms of protein quality control in multiple cell types prior to significant motor neuron death.

Protective role of melatonin on oxidative stress status and RNA expression in cerebral cortex and cerebellum of AbetaPP transgenic mice after chronic exposure to aluminum.

PubMed

García, Tania; Esparza, José L; Giralt, Montserrat; Romeu, Marta; Domingo, José L; Gómez, Mercedes

2010-06-01

Aluminum (Al) has been associated with pro-oxidant effects, as well as with various serious neurodegenerative diseases such as Alzheimer's disease (AD). On the other hand, melatonin (Mel) is a known antioxidant, which can directly act as free radical scavenger, or indirectly by inducing the expression of some genes linked to the antioxidant defense. In this study, 5-month-old AssPP female transgenic (Tg2576) (Tg) and wild-type mice were fed with Al lactate supplemented in the diet (1 mg Al/g diet). Concurrently, animals received oral Mel (10 mg/kg) until the end of the study at 11 months of age. Four treatment groups were included for both Tg and wild-type mice: control, Al only, Mel only, and Al + Mel. At the end of the treatment period, cortex and cerebellum were removed and processed to examine the following oxidative stress markers: reduced glutathione, oxidized glutathione, cytosolic Cu-Zn superoxide dismutase (SOD1), glutathione reductase (GR), glutathione peroxidase, catalase (CAT), and thiobarbituric acid reactive substances. Moreover, the gene expression of SOD1, GR, and CAT was evaluated by real-time RT-PCR. The biochemical changes observed in cortex and cerebellum suggest that Al acted as a pro-oxidant agent. Melatonin exerted an antioxidant action by increasing the mRNA levels of the enzymes SOD1, CAT, and GR evaluated in presence of Al and Mel, independently on the animal model.

Interplay of Cu and oxygen vacancy in optical transitions and screening of excitons in ZnO:Cu films

NASA Astrophysics Data System (ADS)

Darma, Yudi; Seng Herng, Tun; Marlina, Resti; Fauziah, Resti; Ding, Jun; Rusydi, Andrivo

2014-02-01

We study room temperature optics and electronic structures of ZnO:Cu films as a function of Cu concentration using a combination of spectroscopic ellipsometry, photoluminescence, and ultraviolet-visible absorption spectroscopy. Mid-gap optical states, interband transitions, and excitons are observed and distinguishable. We argue that the mid-gap states are originated from interactions of Cu and oxygen vacancy (Vo). They are located below conduction band (Zn4s) and above valence band (O2p) promoting strong green emission and narrowing optical band gap. Excitonic states are screened and its intensities decrease upon Cu doping. Our results show the importance of Cu and Vo driving the electronic structures and optical transitions in ZnO:Cu films.

Hints for Metal-Preference Protein Sequence Determinants: Different Metal Binding Features of the Five Tetrahymena thermophila Metallothioneins

PubMed Central

Espart, Anna; Marín, Maribel; Gil-Moreno, Selene; Palacios, Òscar; Amaro, Francisco; Martín-González, Ana; Gutiérrez, Juan C.; Capdevila, Mercè; Atrian, Sílvia

2015-01-01

The metal binding preference of metallothioneins (MTs) groups them in two extreme subsets, the Zn/Cd- and the Cu-thioneins. Ciliates harbor the largest MT gene/protein family reported so far, including 5 paralogs that exhibit relatively low sequence similarity, excepting MTT2 and MTT4. In Tetrahymena thermophila, three MTs (MTT1, MTT3 and MTT5) were considered Cd-thioneins and two (MTT2 and MTT4) Cu-thioneins, according to gene expression inducibility and phylogenetic analysis. In this study, the metal-binding abilities of the five MTT proteins were characterized, to obtain information about the folding and stability of their cognate- and non-cognate metal complexes, and to characterize the T. thermophila MT system at protein level. Hence, the five MTTs were recombinantly synthesized as Zn2+-, Cd2+- or Cu+-complexes, which were analyzed by electrospray mass spectrometry (ESI-MS), circular dichroism (CD), and UV-vis spectrophotometry. Among the Cd-thioneins, MTT1 and MTT5 were optimal for Cd2+ coordination, yielding unique Cd17- and Cd8- complexes, respectively. When binding Zn2+, they rendered a mixture of Zn-species. Only MTT5 was capable to coordinate Cu+, although yielding heteronuclear Zn-, Cu-species or highly unstable Cu-homometallic species. MTT3 exhibited poor binding abilities both for Cd2+ and for Cu+, and although not optimally, it yielded the best result when coordinating Zn2+. The two Cu-thioneins, MTT2 and MTT4 isoforms formed homometallic Cu-complexes (major Cu20-MTT) upon synthesis in Cu-supplemented hosts. Contrarily, they were unable to fold into stable Cd-complexes, while Zn-MTT species were only recovered for MTT4 (major Zn10-MTT4). Thus, the metal binding preferences of the five T. thermophila MTs correlate well with their previous classification as Cd- and Cu-thioneins, and globally, they can be classified from Zn/Cd- to Cu-thioneins according to the gradation: MTT1>MTT5>MTT3>MTT4>MTT2. The main mechanisms underlying the evolution and specialization of the MTT metal binding preferences may have been internal tandem duplications, presence of doublet and triplet Cys patterns in Zn/Cd-thioneins, and optimization of site specific amino acid determinants (Lys for Zn/Cd- and Asn for Cu-coordination). PMID:25798065

Changing the thickness of two layers: i-ZnO nanorods, p-Cu2O and its influence on the carriers transport mechanism of the p-Cu2O/i-ZnO nanorods/n-IGZO heterojunction.

PubMed

Ke, Nguyen Huu; Trinh, Le Thi Tuyet; Phung, Pham Kim; Loan, Phan Thi Kieu; Tuan, Dao Anh; Truong, Nguyen Huu; Tran, Cao Vinh; Hung, Le Vu Tuan

2016-01-01

In this study, two layers: i-ZnO nanorods and p-Cu2O were fabricated by electrochemical deposition. The fabricating process was the initial formation of ZnO nanorods layer on the n-IGZO thin film which was prepared by sputtering method, then a p-Cu2O layer was deposited on top of rods to form the p-Cu2O/i-ZnO nanorods/n-ZnO heterojunction. The XRD, SEM, UV-VIS, I-V characteristics methods were used to define structure, optical and electrical properties of these heterojunction layers. The fabricating conditions and thickness of the Cu2O layers significantly affected to the formation, microstructure, electrical and optical properties of the junction. The length of i-ZnO nanorods layer in the structure of the heterojunction has strongly affected to the carriers transport mechanism and performance of this heterojunction.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Wenting; Zhang, Qinggang; Wang, Ruiqin

Unsaturated metal species (UMS) confined in nanomaterials play important roles for electron transfer in a wide range of catalytic reactions. However, the limited fabrication methods of UMS restrict their wider catalytic applications. Here in this paper, we report on the synergy of unsaturated Zn and Cu dopants confined in carbon dots (ZnCu-CDs) to produce enhanced electron transfer and photooxidation processes in the doped CDs. The Zn/Cu species chelate with the carbon matrix mainly through Cu-O(N)-Zn-O(N)-Cu complexes. Within this structure, Cu 2+ acts as a mild oxidizer that facilely increases the unsaturated Zn content and also precisely tunes the unsaturated Znmore » valence state to Zn d+, where d is between 1 and 2, instead of Zn. With the help of UMS, electron-transfer pathways are produced, enhancing both the electron donating (7.0 times) and-accepting (5.3 times) abilities relative to conventional CDs. Because of these synergistic effects, the photocatalytic efficiency of CDs in photooxidation reactions is shown to improve more than 5-fold.« less

Comment on "Active sites for CO2 hydrogenation to methanol on Cu/ZnO catalysts".

PubMed

Nakamura, Junji; Fujitani, Tadahiro; Kuld, Sebastian; Helveg, Stig; Chorkendorff, Ib; Sehested, Jens

2017-09-01

Kattel et al (Reports, 24 March 2017, p. 1296) report that a zinc on copper (Zn/Cu) surface undergoes oxidation to zinc oxide/copper (ZnO/Cu) during carbon dioxide (CO 2 ) hydrogenation to methanol and conclude that the Cu-ZnO interface is the active site for methanol synthesis. Similar experiments conducted two decades ago by Fujitani and Nakamura et al demonstrated that Zn is attached to formate rather than being fully oxidized. Copyright © 2017, American Association for the Advancement of Science.

Efficiency enhancement using a Zn1- x Ge x -O thin film as an n-type window layer in Cu2O-based heterojunction solar cells

NASA Astrophysics Data System (ADS)

Minami, Tadatsugu; Nishi, Yuki; Miyata, Toshihiro

2016-05-01

Efficiency enhancement was achieved in Cu2O-based heterojunction solar cells fabricated with a zinc-germanium-oxide (Zn1- x Ge x -O) thin film as the n-type window layer and a p-type Na-doped Cu2O (Cu2O:Na) sheet prepared by thermally oxidizing Cu sheets. The Ge content (x) dependence of the obtained photovoltaic properties of the heterojunction solar cells is mainly explained by the conduction band discontinuity that results from the electron affinity difference between Zn1- x Ge x -O and Cu2O:Na. The optimal value of x in Zn1- x Ge x -O thin films prepared by pulsed laser deposition was observed to be 0.62. An efficiency of 8.1% was obtained in a MgF2/Al-doped ZnO/Zn0.38Ge0.62-O/Cu2O:Na heterojunction solar cell.

Towards Stable CuZnAl Slurry Catalysts for the Synthesis of Ethanol from Syngas

NASA Astrophysics Data System (ADS)

Dong, Weibing; Gao, Zhihua; Zhang, Qian; Huang, Wei

2018-07-01

A stable CuZnAl slurry catalyst for the synthesis of ethanol from syngas has been developed by adjusting the heat treatment conditions of the complete liquid-phase method. The activity evaluation results showed that the CuZnAl catalyst, when heat-treated under a high pressure and temperature, was a stable catalyst for the synthesis of ethanol. The selectivity of ethanol using the CuZnAl slurry catalyst, which was heat-treated at 553 K under 4.0 MPa, increased continuously with time and was stable at approximately 26.00% after 144 h. The characterization results indicated that the CuZnAl slurry catalyst heat-treated under high pressure conditions could facilitate the formation of a more perfect structure with a larger specific surface area. The prepared catalyst contained a balance of strong and weak acid sites, an appropriate form of Cu2O and a high Cu/Zn atomic ratio at the catalyst surface, providing its stability in ethanol synthesis from syngas.

Room temperature ferromagnetism in Cu doped ZnO

NASA Astrophysics Data System (ADS)

Ali, Nasir; Singh, Budhi; Khan, Zaheer Ahmed; Ghosh, Subhasis

2018-05-01

We report the room temperature ferromagnetism in 2% Cu doped ZnO films grown by RF magnetron sputtering in different argon and oxygen partial pressure. X-ray photoelectron spectroscopy was used to ascertain the oxidation states of Cu in ZnO. The presence of defects within Cu-doped ZnO films can be revealed by electron paramagnetic resonance. It has been observed that saturated magnetic moment increase as we increase the zinc vacancies during deposition.

Effect of Gold Nanoparticles Addition to CuO–ZnO/A₂O₃ Catalyst in Conversion of Carbon Dioxide to Methanol.

PubMed

Kim, Ki-Joong; Ahn, Ho-Geun

2017-04-01

Hydrogenation of carbon dioxide (CO₂) into methanol (CH₃OH) was carried out in the CuO–ZnO based supported gold catalyst prepared by the co-precipitation method. When gold nanoparticles were added to the CuO–ZnO/Al2O₃ catalysts (CuO–ZnO/Au/Al₂O₃), the CO₂ conversion and CH₃OH yield were increased (two times higher than that of CuO–ZnO/Al₂O₃ catalyst) with increasing reaction pressure, but selectivity of CH3OH was decreased. The main reason of this result could suggest the importance gold-oxides interface in CH₃OH formation through hydrogenation of CO₂. Maximum selectivity and yield to CH₃OH over CuO–ZnO/Au/Al₂O₃ were obtained at 250°C and under 15–20 bars.

Effect of Cu-Dopant on the Structural, Magnetic and Electrical Properties of ZnO

NASA Astrophysics Data System (ADS)

Aryanto, D.; Kurniawan, C.; Subhan, A.; Sudiro, T.; Sebayang, P.; Ginting, M.; Siregar, S. M. K.; Nasruddin, M. N.

2017-05-01

Zn1- x Cu x O (x = 0, 2, 3, and 4 at.%) was synthesized by using solid-state reaction technique. The ZnO and CuO powders were mixed and then milled by using high-speed shaker mill. The influence of Cu dopants on the structure, magnetic, and electrical properties was investigated by using XRD, VSM, and I-V and C-V measurements. The XRD analysis showed that the Zn1- x Cu x O had hexagonal wurtzite polycrystalline. The diffraction intensity decreased and the peak position shifted directly to a higher 2θ angle with increasing the dopant concentration. Furthermore, the lattice parameters decreased when the ZnO was doped with x = 0.04, which indicated that the crystal structure changed. The increase of Cu dopants was believed to affect the magnetic and electrical properties of ZnO.

Photoluminescence of vapor and solution grown ZnTe single crystals

NASA Astrophysics Data System (ADS)

Biao, Y.; Azoulay, M.; George, M. A.; Burger, A.; Collins, W. E.; Silberman, E.; Su, C.-H.; Volz, M. E.; Szofran, F. R.; Gillies, D. C.

1994-04-01

ZnTe single crystals grown by horizontal physical vapor transport (PVT) and by vertical traveling heater method (THM) from a Te solution were characterized by photoluminescence (PL) at 10.6 K and by atomic force microscopy (AFM). Copper was identified by PL as a major impurity existing in both crystals, forming a substitutional acceptor, Cu Zn. The THM ZnTe crystals were found to contain more Cu impurity than the PVT ZnTe crystals. The formation of Cu Zn-V Te complexes and the effects of annealing, oxygen contamination and intentional Cu doping were also studied. Finally, the surface morphology analyzed by AFM was correlated to the PL results.

Cyclotron production of {sup 61}Cu using natural Zn and enriched {sup 64}Zn targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asad, A. H.; Smith, S. V.; Chan, S.

2012-12-19

Copper-61 ({sup 61}Cu) shares with {sup 64}Cu certain advantages for PET diagnostic imaging, but has a shorter half-life (3.4hr vs. 12.7hr) and a greater probability of positron production per disintegration (61% vs. 17.9%). One important application is for in vivo imaging of hypoxic tissue. In this study {sup 61}Cu was produced using the {sup 64}Zn(p,{alpha}){sup 61}Cu reaction on natural Zn or enriched {sup 64}Zn targets. The enriched {sup 64}Zn (99.82%) was electroplated onto high purity gold or silver foils or onto thin Al discs. A typical target bombardment used 30{mu}A; at 11.7, 14.5 or 17.6MeV over 30-60min. The {sup 61}Cumore » (radiochemical purity of >95%) was separated using a combination of cation and anion exchange columns. The {sup 64}Zn target material was recovered after each run, for re-use. In a direct comparison with enriched {sup 64}Zn-target results, {sup 61}Cu production using the cheaper {sup nat}Zn target proved to be an effective alternative.« less

Fibroblast responses and antibacterial activity of Cu and Zn co-doped TiO2 for percutaneous implants

NASA Astrophysics Data System (ADS)

Zhang, Lan; Guo, Jiaqi; Yan, Ting; Han, Yong

2018-03-01

In order to enhance skin integration and antibacterial activity of Ti percutaneous implants, microporous TiO2 coatings co-doped with different doses of Cu2+ and Zn2+ were directly fabricated on Ti via micro-arc oxidation (MAO). The structures of coatings were investigated; the behaviors of fibroblasts (L-929) as well as the response of Staphylococcus aureus (S. aureus) were evaluated. During the MAO process, a large number of micro-arc discharges forming on Ti performed as penetrating channels; O2-, Ca2+, Zn2+, Cu2+ and PO43- delivered via the channels, giving rise to the formation of doped TiO2. Surface characteristics including phase component, topography, surface roughness and wettability were almost the same for different coatings, whereas, the amount of Cu doped in TiO2 decreased with the increased Zn amount. Compared with Cu single-doped TiO2 (0.77 Wt% Cu), the co-doped with appropriate amounts of Cu and Zn, for example, 0.55 Wt% Cu and 2.53 Wt% Zn, further improved proliferation of L-929, facilitated fibroblasts to switch to fibrotic phenotype, and enhanced synthesis of collagen I as well as the extracellular collagen secretion; the antibacterial properties including contact-killing and release-killing were also enhanced. By analyzing the relationship of Cu/Zn amount in TiO2 and the behaviors of L-929 and S. aureus, it can be deduced that when the doped Zn is in a low dose (<1.79 Wt%), the behaviors of L-929 and S. aureus are sensitive to the reduced amount of Cu2+, whereas, Zn2+ plays a key role in accelerating fibroblast functions and reducing S. aureus when its dose obviously increases from 2.63 to 6.47 Wt%.

Potential risks of copper, zinc, and cadmium pollution due to pig manure application in a soil-rice system under intensive farming: a case study of Nanhu, China.

PubMed

Shi, Jiachun; Yu, Xiulin; Zhang, Mingkui; Lu, Shenggao; Wu, Weihong; Wu, Jianjun; Xu, Jianming

2011-01-01

Heavy metal (copper [Cu], zinc [Zn], and cadmium [Cd]) pollution of soils from pig manures in soil-rice ( L.) systems under intensive farming was investigated, taking Nanhu, China, as the case study area. Two hundred pig manures and 154 rice straws, brown rice samples, and corresponding surface soil (0-15 cm) samples were collected in paddy fields from 150 farms in 16 major villages within the study area. The mean Cu and Zn concentrations in pig manures consistently exceeded the related standard. About 44 and 60% of soil samples exceed the Chinese Soil Cu and Cd Environmental Quality Standards, respectively. The concentration of Cu, Zn, and Cd in brown rice did not exceed the Chinese Food Hygiene Standard. There was a significant positive correlation between total Cu and Zn contents in soil and application rate of pig manures. Strong correlation was observed between the extractable Cu, Zn, and Cd in soil and the Cu, Zn, and Cd contents in the brown rice. The spatial distribution maps of Cu and Zn concentrations in brown rice, straw, and extractable soil Cu and Zn concentration also showed similar geographical trends. Further analyses on heavy metals loading flux and accumulation rates from pig manure applied suggested that Cu and Cd contents in soil currently have already exceeded the maximum permissible limit, and Zn, if still at current manure application rates, will reach the ceiling concentration limits in 9 yr. This study assists in understanding the risk of heavy metals accumulating from pig manure applications to agricultural soils. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Improved Heterojunction Quality in Cu2O-based Solar Cells Through the Optimization of Atmospheric Pressure Spatial Atomic Layer Deposited Zn1-xMgxO

PubMed Central

Ievskaya, Yulia; Hoye, Robert L. Z.; Sadhanala, Aditya; Musselman, Kevin P.; MacManus-Driscoll, Judith L.

2016-01-01

Atmospheric pressure spatial atomic layer deposition (AP-SALD) was used to deposit n-type ZnO and Zn1-xMgxO thin films onto p-type thermally oxidized Cu2O substrates outside vacuum at low temperature. The performance of photovoltaic devices featuring atmospherically fabricated ZnO/Cu2O heterojunction was dependent on the conditions of AP-SALD film deposition, namely, the substrate temperature and deposition time, as well as on the Cu2O substrate exposure to oxidizing agents prior to and during the ZnO deposition. Superficial Cu2O to CuO oxidation was identified as a limiting factor to heterojunction quality due to recombination at the ZnO/Cu2O interface. Optimization of AP-SALD conditions as well as keeping Cu2O away from air and moisture in order to minimize Cu2O surface oxidation led to improved device performance. A three-fold increase in the open-circuit voltage (up to 0.65 V) and a two-fold increase in the short-circuit current density produced solar cells with a record 2.2% power conversion efficiency (PCE). This PCE is the highest reported for a Zn1-xMgxO/Cu2O heterojunction formed outside vacuum, which highlights atmospheric pressure spatial ALD as a promising technique for inexpensive and scalable fabrication of Cu2O-based photovoltaics. PMID:27500923

The effect of Cu/Zn molar ratio on CO{sub 2} hydrogenation over Cu/ZnO/ZrO{sub 2}/Al{sub 2}O{sub 3} catalyst

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaharun, Salina, E-mail: salinashaharun@gmail.com, E-mail: maizats@petronas.com.my; Shaharun, Maizatul S., E-mail: salinashaharun@gmail.com, E-mail: maizats@petronas.com.my; Taha, Mohd F., E-mail: faisalt@petronas.com.my

2014-10-24

Catalytic hydrogenation of carbon dioxide (CO{sub 2}) to methanol is an attractive way to recycle and utilize CO{sub 2}. A series of Cu/ZnO/Al{sub 2}O{sub 3}/ZrO{sub 2} catalysts (CZAZ) containing different molar ratios of Cu/Zn were prepared by the co-precipitation method and investigated in a stirred slurry autoclave system. The catalysts were characterized by temperature-programmed reduction (TPR), field emission scanning electron microscopy-energy dispersive analysis (FESEM-EDX), X-ray diffraction (XRD) and N{sub 2} adsorption-desorption. Higher surface area, SA{sub BET} values (42.6–59.9 m{sup 2}/g) are recorded at low (1) and high (5) Cu/Zn ratios with the minimum value of 35.71 m{sup 2}/g found formore » a Cu/Zn of 3. The reducibility of the metal oxides formed after calcination of catalyst samples was also affected due to change in metal-support interaction. At a low reaction temperature of 443 K, total gas pressure of 3.0 MPa and 0.1 g/mL of the CZAZ catalyst, the selectivity to methanol decreased as the Cu/Zn molar ratio increased, and the maximum selectivity of 67.73 was achieved at Cu/Zn molar ratio of 1. With a reaction time of 3h, the best performing catalyst was CZAZ75 with Cu/Zn molar ratio of 5 giving methanol yield of 79.30%.« less