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Sample records for dismutase mimics synthesis

  1. Synthesis, Structural Diversity and Mimic Superoxide Dismutase of Mn(II) Complexes Derived from N, O-donor Schiff bases.

    Science.gov (United States)

    Qin, Jie; Yin, Qiang; Zhao, Shan-Shan; Wang, Jun-Zheng; Qian, Shao-Song

    2016-01-01

    Two new potentially tetradentate Schiff base ligands N'-(pyridin-2-ylmethylene)nicotinohydrazide (L1), and N'-(pyridin-2-ylmethylene)isonicotinohydrazide (L(2)) were synthesized. Reactions of hydrazone ligands L(1) and L(2) with Mn(NO(3))(2) afford two mononuclear Mn(II) complexes, [Mn(L(1))(NO(3))(H(2)O)(2)]•(NO(3)) (1) and [Mn(L(2))(2)(NO(3))(H(2)O)]•(NO(3)) (2). For complexes 1 and 2, L(1) and L(2) act as pincer-like tridentate or bidentate ligands, respectively. The Mn(II) ions in the two compounds are both in heptacoordinated environment, while the two molecules display diverse solid-state supramolecular structures because of the different orientation of Npyridine and hydrogen bonding patterns of nitrate anions. Complex 1 features 2D supramolecular sheet, while complex 2 is double-chain supramolecular structure. Both of the two complexes exhibit moderate superoxide dismutase (SOD) mimetic activity.

  2. Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend life span of Saccharomyces cerevisiae.

    Science.gov (United States)

    Ribeiro, Thales de P; Fonseca, Fernanda L; de Carvalho, Mariana D C; Godinho, Rodrigo M da C; de Almeida, Fernando Pereira; Saint'Pierre, Tatiana D; Rey, Nicolás A; Fernandes, Christiane; Horn, Adolfo; Pereira, Marcos D

    2017-01-15

    Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl2]NO3, [Cu(HPClNOL)(CH3CN)](ClO4)2 and Mn(HPClNOL)(Cl)2}, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's.

  3. Stereocontrolled Synthesis of Methyl Silanediol Peptide Mimics

    DEFF Research Database (Denmark)

    Nielsen, Lone; Lindsay, Karl; Faber, Jesper;

    2007-01-01

    with methanolic HCl and the resulting amine extended into peptide chains accordingly. The diphenylsilyl moiety is a resilient protecting group for the corresponding silanediol, which can be unmasked via treatment with TfOH, followed by aqueous hydrolysis. The crude silanediol may be isolated and purified as its...... corresponding bis-TMS siloxane via protection with TMSCl, and converted back to the desired silanediol via hydrolysis with aqueous KOH. Efforts to apply this approach to biologically relevant silanediol peptide mimics, with a view to protease inhibition, are described....

  4. Effects of mimic of manganese superoxide dismutase on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats.

    Science.gov (United States)

    Wang, Yan-Hong; Dong, Jiao; Zhang, Jian-Xin; Zhai, Jing; Ge, Bin

    2016-09-01

    The mimic of manganese superoxide dismutase (MnSODm) has been synthesized and reported to have anti-inflammatory properties. However, whether MnSODm has anti-inflammatory effects on colitis and any underlying mechanisms are poorly understood. This study was to investigate therapeutic effects and mechanism of MnSODm on 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model in rats. Rats were intragastrically administered MnSODm (10, 20, and 40 mg/kg) per day for 7 days after colitis was induced by TNBS. After treated with MnSODm, the colonic macroscopic and microscopic damage scores and colonic weight/length ratios were significantly decreased compared with colitis model group. Myeloperoxidase (MPO) activity, malonyldialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 levels in colon tissues were also significantly decreased in MnSODm treatment groups. However, superoxide dismutase (SOD) activity significantly increased and phosphorylated inhibitory kappa B-alpha (IκBα), inhibitor kappa B kinase (IKKα/β), and nuclear factor-kappa Bp65 (NF-κBp65) as well as Toll-like receptor 4 (TLR4) and myeloid differentiation actor 88 (MyD88) in the colonic mucosa were significantly inhibited by MnSODm treatment. Thus, MnSODm was protective against colitis via antioxidant activity and by inhibiting inflammatory mediators by down-regulating TLR4/MyD88/NF-κB signaling pathways. These data suggest a potential therapeutic effect of MnSODm in colitis.

  5. Insight into the structure and mechanism of nickel-containing superoxide dismutase derived from peptide-based mimics.

    Science.gov (United States)

    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

  6. A Study on Some Copper(Ⅱ) Complexes of Polyaza Cryptandsand Planar Macrocycles-Synthesis, Characterization and Superoxide Dismutase Activity

    Institute of Scientific and Technical Information of China (English)

    GAO, You-Liang; SHEN, Cheng-Yu; TANG, Yin-Yan; LUO, Qin-Hui; YU, Shu-Yan

    2001-01-01

    Two kinds of macrocyclic copper(Ⅱ) complexes were synthesized. One of them is composed of copper(Ⅱ) cryptates of ligands L1-L4 which are condensation products of 5-R-2methoxy-1,3-phenyldialdehyde (R= OCH3, L1) with tris(2-aminoethyl)amine and 5-R-2-methothoxy-1, 3-phenyldialdehyde (R = CH3, L3) with tris(2-aminopropyi)amine as well as their reduced products of L1 and L3 (L2 and L4). The other is composed of two-dimensional macrocyclic copper(Ⅱ) complexcs of ligands L5-L8 of condensation products of diethylene triamine with 4-R-1-methoxy-2, 6-phenyldialdehyde (R = Cl,Br, CH3, OCH3). Therelationship between their structurcs and superoxide dismutase (SOD) activity was investigated.The results can provide some clues to the synthesis of SOD mimics.

  7. Synthesis of aminocyclopentanols: a-D-galacto configured sugar mimics

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Lundt, Inge

    2005-01-01

    Four aminocyclopentanols, as mimics of putative intermediates in hydrolysis of a-D-galactosides, have been synthesized through a number of stereoselective transformations, using the cis-fused cyclopentane-1,4-lactone (1R, 5S, 7R, 8R)-7,8-dihydroxy-2-oxabicyclo[3.3.0]oct-3-one 1 as a chiral building...

  8. Synthesis of aminocyclopentanols: a-D-galacto configured sugar mimics

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Lundt, Inge

    2005-01-01

    Four aminocyclopentanols, as mimics of putative intermediates in hydrolysis of a-D-galactosides, have been synthesized through a number of stereoselective transformations, using the cis-fused cyclopentane-1,4-lactone (1R, 5S, 7R, 8R)-7,8-dihydroxy-2-oxabicyclo[3.3.0]oct-3-one 1 as a chiral buildi...

  9. CRADA Final Report: Mucin Mimic and Glycopeptide Synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Bertozzi, Carolyn R.

    2002-10-22

    Mucus has several constituents but the most important are the mucins, heavily O-glycosylated proteins characterized by long stretches of tandem repeat sequences rich in glycosylated serine and threonine residues, with N- and C-terminal domains that have determined to a large extent by the viscous and viscoelastic properties of mucin glycoproteins. Indeed, these properties are evident in reconstituted purified mucin glycoproteins. Oligomeric mucin can be deconstructed into its monomeric components and then further into the domains that comprise each mucin molecule. There are two major domain types. "Glycodomains" are defined by stretches of the tandemly repeated Thr/Ser-rich segments that bear the characteristic O-linked glycans of the mucin molecule. The goal of this project is to synthesize polymeric materials that mimic mucin glycodomains. In order to mimic the central features of mucin, these materials should have dense clusters of glycans that bear a similar structure to those found in native mucins, and a fairly rigid polymer backbone. Four different polymers bearing ketone groups for the attachment of sugars were synthesized. GalNAc{alpha}-ONH{sub 2} and Sia{alpha}2,6GaINAc{alpha}·ONH{sub 2} both of which could be ligated to the polymer scaffolds were synthesized. Mucin glycodomain mimics were successfully synthesized by ligation of glycans to polymers.

  10. Addition of superoxide dismutase mimics during cooling process prevents oxidative stress and improves semen quality parameters in frozen/thawed ram spermatozoa.

    Science.gov (United States)

    Santiani, Alexei; Evangelista, Shirley; Sepúlveda, Néstor; Risopatrón, Jennie; Villegas, Juana; Sánchez, Raúl

    2014-10-01

    High levels of reactive oxygen species (ROS), which may be related to reduced semen quality, are detected during semen cryopreservation in some species. The objectives of this study were to measure the oxidative stress during ram semen cryopreservation and to evaluate the effect of adding 2 antioxidant mimics of superoxide dismutase (Tempo and Tempol) during the cooling process on sperm motility, viability, acrosomal integrity, capacitation status, ROS levels, and lipid peroxidation in frozen and/or thawed ram spermatozoa. Measuring of ROS levels during the cooling process at 35, 25, 15, and 5 °C and after freezing and/or thawing showed a directly proportional increase (P ram spermatozoa are exposed to oxidative stress during the cooling process, specifically when maintained at 5 °C and that lipid peroxidation induced by high levels of ROS decreases sperm motility and induces premature sperm capacitation. In contrast, the addition of Tempo or Tempol at 0.5 to 1 mM during the cooling process (10 °C) protects ram spermatozoa from oxidative stress.

  11. Synthesis of substituted benzimidazolyl curcumin mimics and their anticancer activity.

    Science.gov (United States)

    Woo, Ho Bum; Eom, Young Woo; Park, Kyu-Sang; Ham, Jungyeob; Ahn, Chan Mug; Lee, Seokjoon

    2012-01-15

    A novel curcumin mimic library (14a-14h and 15a-15h) possessing variously substituted benzimidazole groups was synthesized through the aldol reaction of (E)-4-(4-hydroxy-3-methoxyphenyl)but-3-en-2-one (7) or (E)-4-(3-hydroxy-4-methoxyphenyl)but-3-en-2-one (13) with diversely substituted benzimidazolyl-2-carbaldehyde (12a-12h). The MTT assay of the cancer cells MCF-7, SH-SY5Y, HEP-G2, and H460 showed that compound 14c with IC(50) of 1.0 and 1.9μM has a strong inhibitory effect on the growth of SH-SY5Y and Hep-G2 cells, respectively, and that compound 15h with IC(50) of 1.9μM has a strong inhibitory effect on the growth of MCF-7 cancer cells.

  12. Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

    Directory of Open Access Journals (Sweden)

    Markus Leibeling

    2013-10-01

    Full Text Available A synthesis of anthracycline aglycone derivatives is described. The key step utilizes a powerful domino carbopalladation approach and subsequent ring closure. During this process two of the four rings of the anthracycline scaffold are formed. Differently substituted carbohydrates and dialkyne chains serve as versatile and simple starting materials for the reaction sequence. Diverse building blocks lead to a variety of different products and a broad range of structural diversity.

  13. Synthesis of oxime-linked mucin mimics containing thetumor-related TN and sialyl TN antigens

    Energy Technology Data Exchange (ETDEWEB)

    Marcaurelle, Lisa A.; Shin, Youngsook; Goon, Scarlett; Bertozzi,Carolyn R.

    2001-08-21

    The synthesis of oxime-linked mucin mimics was accomplished via the incorporation of multiple ketone residues into a peptide followed by reaction with aminooxy sugars corresponding to the tumor-related T{sub N} and sialyl T{sub N} (ST{sub N}) antigens.

  14. Superoxide dismutase mimic, MnTE-2-PyP5+ ameliorates acute and chronic proctitis following focal proton irradiation of the rat rectum

    Directory of Open Access Journals (Sweden)

    John O. Archambeau

    2013-01-01

    Full Text Available Radiation proctitis, an inflammation and damage to the lower part of colon, is a common adverse event of the radiotherapy of tumors in the abdominal and pelvic region (colon, prostate, cervical. Several Mn(III porphyrin-based superoxide dismutase mimics have been synthesized and successfully evaluated in preclinical models as radioprotectants. Here we report for the first time the remarkable rectal radioprotection of frequently explored Mn(III meso-tetrakis(N-ethylpyridinium-2-ylporphyrin, MnTE-2-PyP5+. A batch prepared in compliance with good manufacturing practice (GMP, which has good safety/toxicity profile, was used for this study. MnTE-2-PyP5+ was given subcutaneously at 5 mg/kg, either 1 h before or 1 h after irradiation, with additional drug administered at weekly intervals thereafter. MnTE-2-PyP5+ ameliorated both acute and chronic radiation proctitis in male Sprague-Dawley rats irradiated with 20–30 Gy protons delivered to 2.5 cm span of rectum using spread-out Bragg peak of a proton treatment beam. Focal irradiation of the rectum produced acute proctitis, which healed, followed by chronic rectal dilation and symptomatic proctitis. MnTE-2-PyP5+ protected rectal mucosa from radiation-induced crypt loss measured 10 days post-irradiation. Significant effects were observed with both pre- and post-treatment regimens. However, only MnTE-2-PyP5+ pre-treatment, but not post-treatment, prevented the development of rectal dilation, indicating that proper dosing regimen is critical for radioprotection. The pre-treatment also prevented or delayed the development of chronic proctitis depending on the radiation dose. Further work aimed at developing MnTE-2-PyP5+ and similar drugs as adjunctive agents for radiotherapy of pelvic tumors is warranted. The present study substantiates the prospects of employing this and similar analogs in preserving normal tissue during cancer radiation as well as any other radiation exposure.

  15. The Superoxide Dismutase Mimics of Metal Complexes of Schiff-bases%席夫碱金属SOD模型配合物

    Institute of Scientific and Technical Information of China (English)

    李金芳; 屠淑洁; 周荫庄

    2005-01-01

      The design and application of the synthesis of low molecular weight metal complexes containing Cu, Zn, Mn etc. as SOD mimics have received considerable attention during the last decades. Large number of the complexes of Cu, Zn, Mn etc with various donor ligands have been characterized as O promising models of the enzyme, including Schiff-base ligands.The results showed that the Schiff-base complexes exhibited that the abilities of eliminating•2 O are much higher than that of other•2 kinds of complexes. The research progress in the studies of the SOD model complexes with Schiff-base ligands and its biological activities have been introduced in this paper.%  席夫碱为配体的Cu、Zn、Mn等单核、双核配合物对•2O 的清除表现出一定的活性且明显高于非席夫碱单核及双核配合物。近年来该领域新化合物的合成、结构表征及构效关系的研究甚为活跃,对CuZn-SOD、Mn-SOD、Fe-SOD的席夫碱SOD模型配合物的研究已取得进展。本文介绍了席夫碱金属SOD模型配合物的合成、表征及相关活性的研究进展。

  16. Synthesis and biological activity of conformationally restricted gypsy moth pheromone mimics.

    Science.gov (United States)

    Chen, Hao; Gong, Yongmei; Gries, Regine M; Plettner, Erika

    2010-04-15

    The design and synthesis of a series of conformationally constrained mimics of gypsy moth sex pheromone, (+)-disparlure (7R,8S)-2-methyl-7,8-epoxyoctadecane, are described. The core structure of the mimics is derived from 5-(2'-hydroxyethyl)cyclopent-2-en-1-ol. Substituent optimization of the analogs was accomplished through the synthesis of mini-libraries and pure individual compounds, followed by electrophysiological experiments with male gypsy moth antennae. The electroantennogram results show that the analogs elicited weak to no antennal responses themselves. There was a clear structure-activity pattern for odorant activity, with ethyl substituents being best. Further, when puffed simultaneously with the pheromone, some of the compounds gave a significant enhancement of the antennal depolarization, indicating an additive or synergistic effect. A pure pheromone stimulus following a mixed compound/pheromone stimulus was generally not affected, with two exceptions: one compound enhanced and another inhibited a subsequent stimulus. The compounds also prolonged the stimulation of the antenna, which manifested itself in widened electroantennogram peaks. We tested the hypothesis that this prolonged stimulation may be due to the stabilization of a particular conformer of the pheromone-binding protein (PBP). Compounds that caused PBP2 to adopt a similar conformation than in the presence of pheromone also caused peak widening. This was not the case with PBP1.

  17. Inhibition effect of expression of Cu/Zn superoxide dismutase from rice on synthesis of Glutathione in Saccharomyces cerevisiae

    Institute of Scientific and Technical Information of China (English)

    AI Yu-zhuo; DU Ye-jie; ZU Yuan-gang; AN Zhi-gang

    2008-01-01

    The expression of a rice Cu/Zn superoxide dismutase (Cu/Zn-SOD) in Saccharomyces cerevisiae regulated by GAPDH promoter, involved in the inhibition of endogenous Glutathione (GSH) synthesis, and the competitive expression was detected by constructing the expression vector transferred Cu/Zn-SOD gene into wild-type S. Cerevisiae. Transcription and expression of the Cu/Zn-SOD gene in S. Cerevisiawere were confirmed by northern blot and SDS-PAGE, respectively, and activity of the Cu/Zn-SOD from crude extracts was enzymatically detected based on the effect of nitroblue tetrazolium (NBT) after running a native polyacrylamide gel. The GSH synthesis was also tested by DTNB (5, 5′-Dithiobis (2-nitrobenzoic acid)) method. Results showed that GSH synthesis was evidently suppressed by the expression of Cu/Zn-SOD gene in both control and heat shock strains. It implied that the expression of the Cu/Zn-SOD gene in S. Cerevisiae has more potential facility in response to oxidative exposure than that of endogenous GSH, although Cu/Zn-SOD and GSH were both contributed to the function of oxygen radical oxidoreduction.

  18. Pharmacokinetics, tissue distribution and excretion of manganese (III) meso-tetra [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, a novel superoxide dismutase mimic, in Wistar rats.

    Science.gov (United States)

    Li, Bao-Qiu; Fang, Shi-Hong; Dong, Xin; Li, Na; Gao, Ji-You; Yang, Gui-Qin; Gong, Xian-Chang; Wang, Shu-Juan; Wang, Feng-Shan

    2013-12-01

    Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel superoxide dismutase mimic. It exhibits strong free-radical scavenging activities in vitro and in vivo. The aim of the present study was to investigate the pharmacokinetics, tissue distribution and excretion of HSJ-0017 in Wistar rats following a single intravenous administration. Wistar rats were given different doses of HSJ-0017 by single intravenous injection. Biological samples of rats were collected and were assayed by the HPLC method. The pharmacokinetics, tissue distribution and excretion of HSJ-0017 were investigated. The pharmacokinetic data of HSJ-0017 in rats following intravenous injection was best-fit by a two-compartment model. T max of HSJ-0017 in plasma following intravenous injection was 0.083 h. AUC and plasma drug concentration were found to increase in a dose-related fashion. The highest concentrations of HSJ-0017 were detected in the liver (82.25 ± 13.99 μg/g) of rats, followed by the kidney, small intestine, lung, plasma, heart, spleen, and stomach within 2 h postdose. No HSJ-0017 was detected in the uterus, parorchis or brain of rats during the 24-h period of examination. The total cumulative excretion of HSJ-0017 in rat bile and urine were found to be 78.85 and 67.58 %, respectively. Our study has led to the view that the HSJ-0017 can be rapidly distributed to tissues after intravenous administration, but cannot diffuse through the blood-brain barrier. The faecal and biliary excretion of unchanged HSJ-0017 are the major routes of HSJ-0017 elimination.

  19. Synthesis, Electrochemical, Spectroscopic, Antimicrobial, and Superoxide Dismutase Activity of Nickel (II Complexes with Bidentate Schiff Bases

    Directory of Open Access Journals (Sweden)

    R. N. Patel

    2013-01-01

    Full Text Available Five new nickel (II complexes, namely, [Ni(L12](ClO42(1; [Ni(L22](ClO42(2; [Ni(L32](ClO42(3; [Ni(L42](ClO42(4; [Ni(L52](ClO42(5, where L1 = benzoylhydrazide; L2 = N-[(1-1-(2-methylphenylethylidene]benzohydrazide; L3=N-[(1-1-(4-methylphenylethylidene]benzohydrazide; L4=N-[(1-1-(2-methoxyphenylethylidene]benzohydrazide; L5 = N-[(1-1-(4-methoxy-phenylethylidene]benzohydrazide, have been synthesized and characterized by various physicochemical and spectroscopic techniques. The synthesized complexes are stable powders, insoluble in common organic solvents such as ethanol, benzene, carbon tetrachloride, chloroform, and diethyl ether, and are nonelectrolytes. The magnetic and spectroscopic data indicate a distorted square planar geometry for all complexes. The superoxide dismutase activity of these complexes has been measured and discussed. Antibacterial and antifungal properties of these complexes were also tested.

  20. Retro-Curcuminoids as Mimics of Dehydrozingerone and Curcumin: Synthesis, NMR, X-ray, and Cytotoxic Activity

    OpenAIRE

    2016-01-01

    Curcumin and its derivatives have been extensively studied for their remarkable medicinal properties, and their chemical synthesis has been an important step in the optimization of well-controlled laboratory production. A family of new compounds that mimic the structure of curcumin and curcuminoids, here named retro-curcuminoids (7–14), was synthesized and characterized using 1D 1H- and 13C-NMR, IR, and mass spectrometry; the X-ray structure of 7, 8, 9, 10, 12, 13, and 14 are reported here fo...

  1. Synthesis of high-mannose oligosaccharide analogues through click chemistry: true functional mimics of their natural counterparts against lectins?

    Science.gov (United States)

    François-Heude, Marc; Méndez-Ardoy, Alejandro; Cendret, Virginie; Lafite, Pierre; Daniellou, Richard; Ortiz Mellet, Carmen; García Fernández, José M; Moreau, Vincent; Djedaïni-Pilard, Florence

    2015-01-26

    Terminal "high-mannose oligosaccharides" are involved in a broad range of biological and pathological processes, from sperm-egg fusion to influenza and human immunodeficiency virus infections. In spite of many efforts, their synthesis continues to be very challenging and actually represents a major bottleneck in the field. Whereas multivalent presentation of mannopyranosyl motifs onto a variety of scaffolds has proven to be a successful way to interfere in recognition processes involving high-mannose oligosaccharides, such constructs fail at reproducing the subtle differences in affinity towards the variety of protein receptors (lectins) and antibodies susceptible to binding to the natural ligands. Here we report a family of functional high-mannose oligosaccharide mimics that reproduce not only the terminal mannopyranosyl display, but also the core structure and the branching pattern, by replacing some inner mannopyranosyl units with triazole rings. Such molecular design can be implemented by exploiting "click" ligation strategies, resulting in a substantial reduction of synthetic cost. The binding affinities of the new "click" high-mannose oligosaccharide mimics towards two mannose specific lectins, namely the plant lectin concanavalin A (ConA) and the human macrophage mannose receptor (rhMMR), have been studied by enzyme-linked lectin assays and found to follow identical trends to those observed for the natural oligosaccharide counterparts. Calorimetric determinations against ConA, and X-ray structural data support the conclusion that these compounds are not just another family of multivalent mannosides, but real "structural mimics" of the high-mannose oligosaccharides.

  2. Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT)

    Science.gov (United States)

    2015-01-01

    3-Hydroxy-4-pyridinones and 5-hydroxy-4-pyrimidinones were identified as inhibitors of catechol-O-methyltransferase (COMT) in a high-throughput screen. These heterocyclic catechol mimics exhibit potent inhibition of the enzyme and an improved toxicity profile versus the marketed nitrocatechol inhibitors tolcapone and entacapone. Optimization of the series was aided by X-ray cocrystal structures of the novel inhibitors in complex with COMT and cofactors SAM and Mg2+. The crystal structures suggest a mechanism of inhibition for these heterocyclic inhibitors distinct from previously disclosed COMT inhibitors. PMID:25815153

  3. Synthesis of Oxylipin Mimics and Their Antifungal Activity against the Citrus Postharvest Pathogens

    Directory of Open Access Journals (Sweden)

    Jimei Ma

    2016-02-01

    Full Text Available Nine oxylipin mimics were designed and synthesized starting from d-mannose. Their antifungal activity against three citrus postharvest pathogens was evaluated by spore germination assay. The results indicated that all the compounds significantly inhibited the growth of Penicillium digitatum, Penicillium italicum and Aspergillus niger. The compound (3Z,6Z,8S,9R,10R-octadeca-3,6-diene-8,9,10-triol (3 exhibited excellent inhibitory effect on both Penicillium digitatum (IC50 = 34 ppm and Penicillium italicum (IC50 = 94 ppm. Their in vivo antifungal activities against citrus postharvest blue mold were tested with fruit inoculated with the pathogen Penicillium italicum. The compound (3R,4S-methyl 3,4-dihydroxy-5-octyltetrahydrofuran-2-carboxylate (9 demonstrated significant efficacy by reducing the disease severity to 60%. The antifungal mechanism of these oxylipin mimics was postulated in which both inhibition of pathogenic mycelium and stimuli of the host oxylipin-mediated defense response played important roles.

  4. Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe.

    Science.gov (United States)

    Plutschack, Matthew B; McQuade, D Tyler; Valenti, Giulio; Seeberger, Peter H

    2013-01-01

    We describe the synthesis of 1-amino-2,5-anhydro-D-mannose ("mannitolamine"), a key intermediate to the 7-nitro-1,2,3-benzadiazole conjugate (NBDM), using commercially available fluidic devices to increase the throughput. The approach is the first example of a flow-based Tiffeneau-Demjanov rearrangement. Performing this step in flow enables a ~64-fold throughput enhancement relative to batch. The flow process enables the synthesis to be accomplished three times faster than the comparable batch route. The high throughput enabled the production of larger quantities of the fluorescent fructose transport probe NBDM, enabling us to measure key photophysical properties that will facilitate future uptake studies.

  5. Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe

    Directory of Open Access Journals (Sweden)

    Matthew B. Plutschack

    2013-10-01

    Full Text Available We describe the synthesis of 1-amino-2,5-anhydro-D-mannose (“mannitolamine”, a key intermediate to the 7-nitro-1,2,3-benzadiazole conjugate (NBDM, using commercially available fluidic devices to increase the throughput. The approach is the first example of a flow-based Tiffeneau–Demjanov rearrangement. Performing this step in flow enables a ~64-fold throughput enhancement relative to batch. The flow process enables the synthesis to be accomplished three times faster than the comparable batch route. The high throughput enabled the production of larger quantities of the fluorescent fructose transport probe NBDM, enabling us to measure key photophysical properties that will facilitate future uptake studies.

  6. ROMP- and RAFT-Based Guanidinium-Containing Polymers as Scaffolds for Protein Mimic Synthesis.

    Science.gov (United States)

    Sarapas, Joel M; Backlund, Coralie M; deRonde, Brittany M; Minter, Lisa M; Tew, Gregory N

    2017-05-17

    Cell-penetrating peptides are an important class of molecules with promising applications in bioactive cargo delivery. A diverse series of guanidinium-containing polymeric cell-penetrating peptide mimics (CPPMs) with varying backbone chemistries was synthesized and assessed for delivery of both GFP and fluorescently tagged siRNA. Specifically, we examined CPPMs based on norbornene, methacrylate, and styrene backbones to determine how backbone structure impacted internalization of these two cargoes. Either charge content or degree of polymerization was held constant at 20, with diguanidinium norbornene molecules being polymerized to both 10 and 20 repeat units. Generally, homopolymer CPPMs delivered low amounts of siRNA into Jurkat T cells, with no apparent backbone dependence; however, by adding a short hydrophobic methyl methacrylate block to the guanidinium-rich methacrylate polymer, siRNA delivery to nearly the entire cell population was achieved. Protein internalization yielded similar results for most of the CPPMs, though the block polymer was unable to deliver proteins. In contrast, the styrene-based CPPM yielded the highest internalization for GFP (≈40 % of cells affected), showing that indeed backbone chemistry impacts protein delivery, specifically through the incorporation of an aromatic group. These results demonstrate that an understanding of how polymer structure affects cargo-dependent internalization is critical to designing new, more effective CPPMs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Scleroderma mimics.

    Science.gov (United States)

    Nashel, Jennifer; Steen, Virginia

    2012-02-01

    Scleroderma is a rare systemic autoimmune disease with multiple organ manifestations, including skin fibrosis. The groups of disorders classified as scleroderma mimics share the common thread of skin thickening but are otherwise quite incongruous in terms of underlying disease process and other organ involvement. This article reviews the clinical presentation, etiology, and treatment options available for scleroderma mimics, including morphea, scleredema, diabetic cheiroarthropathy, scleromyxedema, nephrogenic systemic fibrosis, and eosinophilic fasciitis. Through greater understanding of these diseases and the associated extradermal implications, we hope to facilitate recognition of scleroderma and its mimics.

  8. Retro-Curcuminoids as Mimics of Dehydrozingerone and Curcumin: Synthesis, NMR, X-ray, and Cytotoxic Activity

    Directory of Open Access Journals (Sweden)

    Marco A. Obregón-Mendoza

    2016-12-01

    Full Text Available Curcumin and its derivatives have been extensively studied for their remarkable medicinal properties, and their chemical synthesis has been an important step in the optimization of well-controlled laboratory production. A family of new compounds that mimic the structure of curcumin and curcuminoids, here named retro-curcuminoids (7–14, was synthesized and characterized using 1D 1H- and 13C-NMR, IR, and mass spectrometry; the X-ray structure of 7, 8, 9, 10, 12, 13, and 14 are reported here for the first time. The main structural feature of these compounds is the reverse linkage of the two aromatic moieties, where the acid chloride moiety is linked to the phenolic group while preserving α, β-unsaturated ketone functionality. The cytotoxic screening of 7, 8, 9, and 10 at 50 and 10 µg/mL was carried out with human cancer cell lines K562, MCF-7, and SKLU-1. Lipid peroxidation on rat brain was also tested for compounds 7 and 10. Compounds 7, 8, and 10 showed relevant cytotoxic activity against these cancer cell lines, and 10 showed a protective effect against lipid peroxidation. The molecular resemblance to curcuminoids and analogs with ortho substituents suggests a potential source of useful bioactive compounds.

  9. Models of Superoxide Dismutases

    Energy Technology Data Exchange (ETDEWEB)

    Cabelli, Diane E.; Riley, Dennis; Rodriguez, Jorge A.; Valentine, Joan Selverstone; Zhu, Haining

    1998-05-20

    In this review we have focused much of our discussion on the mechanistic details of how the native enzymes function and how mechanistic developments/insights with synthetic small molecule complexes possessing SOD activity have influenced our understanding of the electron transfer processes involved with the natural enzymes. A few overriding themes have emerged. Clearly, the SOD enzymes operate at near diffusion controlled rates and to achieve such catalytic turnover activity, several important physical principles must be operative. Such fast electron transfer processes requires a role for protons; i.e., proton-coupled electron transfer (''H-atom transfer'') solves the dilemma of charge separation developing in the transition state for the electron transfer step. Additionally, outer-sphere electron transfer is likely a most important pathway for manganese and iron dismutases. This situation arises because the ligand exchange rates on these two ions in water never exceed {approx}10{sup +7} s{sup -1}; consequently, 10{sup +9} catalytic rates require more subtle mechanistic insights. In contrast, copper complexes can achieve diffusion controlled (>10{sup +9}) exchange rates in water; thus inner-sphere electron transfer processes are more likely to be operative in the Cu/Zn enzymes. Recent studies have continued to expand our understanding of the mechanism of action of this most important class of redox active enzymes, the superoxide dismutases, which have been critical in the successful adaptation of life on this planet to an oxygen-based metabolism. The design of SOD mimic drugs, synthetic models compounds that incorporate this superoxide dismutase catalytic activity and are capable of functioning in vivo, offers clear potential benefits in the control of diseases, ranging from the control of neurodegenerative conditions, such as Parkinson's or Alzheimer's disease, to cancer.

  10. Synthesis and characterization of a monomeric mutant Cu/Zn superoxide dismutase with partially reconstituted enzymic activity.

    Science.gov (United States)

    Banci, L; Bertini, I; Chiu, C Y; Mullenbach, G T; Viezzoli, M S

    1995-12-15

    A monomeric analog of human Cu/Zn superoxide dismutase (F50E/G51E SOD), previously characterized and found to have reduced enzymic activity, was here further modified by replacing Glu133 with Gln. This substitution does not dramatically affect the coordination geometry at the active site, but enhances enzymic activity, and also increases the affinity for anions at the active site. This behavior parallels earlier published results in which this point mutation was made in the dimeric wild-type enzyme. The analog described here has afforded for the first time a monomeric superoxide dismutase with substantial activity. This point mutation does not significantly influence the protein structure but interactions with anions, including superoxide, are altered with respect to the monomeric form. The present monomeric Glu133Gln mutant has partially restored enzymic activity. The diminished activity of the monomeric analogs is discussed in the light of possible minor structural changes and some of their characteristics are compared with those of naturally occurring mutants associated with various neurological diseases.

  11. Synthesis, characterization and superoxide dismutase activity of bi-copper(II)-bisacetato-−phthalicacid[bis(benzyloxy)ethyl]ester

    Indian Academy of Sciences (India)

    Babita Sarma; Pradip K Bhattacharyya; Diganta Kumar Das

    2015-03-01

    A new binuclear copper(II) complex, bridged by the ligand phthalicacid[bis(benzyloxy)ethyl]ester, where each copper(II) is coordinated to one carboxylate (from ligand) and one acetate in square planar mode is reported. The ligand synthesized by the reaction of phthalic anhydride and ethylene glycol, has been characterized by FT-IR, 1HNMR and LCMS. The binuclear Copper(II) complex has been characterized by UV/visible spectra, FTIR spectra, EPR spectra, ESI-MS spectra, magnetic moment measurement and thermogravimetric analysis. DFT calculation has shown a Z type structure for the complex. Excellent superoxide dismutase activity with IC50 value 8.6 × 10−6 M for the complex has been observed.

  12. Synthesis of Pyridinic-Rich N, S Co-doped Carbon Quantum Dots as Effective Enzyme Mimics

    Science.gov (United States)

    Liu, Teng; Cui, Zhi-wei; Zhou, Jun; Wang, Ying; Zou, Zhi-gang

    2017-05-01

    N and S co-doped carbon quantum dots (N, S-CQDs) with high N- and S-doping level were synthesized by microwave solid-phase pyrolysis within 50 s. Owing to the dominant pyridinic N injection into the conjugated framework, both high enzyme mimics catalytic activity and photoluminescence quantum yield are achieved simultaneously.

  13. Synthesis and Kinetics of a Novel Mimic with Glutathione Peroxidase Activity-Tellurium-containing Hyaluronic Acid (TeHA)

    Institute of Scientific and Technical Information of China (English)

    Zhi Bo CHEN; Lan Ying LIU; Bo Xun ZHANG; Zhong Xiu HUANG; Qing Lin PENG; Jia CHEN; Yu WANG; Jian Guo ZHANG; Guang Zhi JIANG; Wen Shu LI

    2006-01-01

    A novel mimic was synthesized by modifying hyaluronic acid (HA) with tellurium,whose function is similar to that of glutathione peroxidase (GPX). The structure of TeHA was characterized by means of IR and NMR, the target-Te was located at -CH2OH of the N-acetyl-D-glucosamine of HA. The H2O2 reducing activity of TeHA, by glutathione (GSH), was 163.6U/μmol according to Wilson's method. In contrast to other mimics, TeHA displayed the highest activity. Moreover, TeHA accepted many hydroperoxides as its substrates, such as H2O2, cumenyl hydroperoxide (CuOOH) and tert-butyl hydroperoxide (t-BuOOH), and CuOOH was the optimal substrate of TeHA. A ping-pong mechanism was observed in the steady-state kinetic studies of the reactions catalyzed by TeHA.

  14. Synthesis and characterization of a lubricin mimic (mLub) to reduce friction and adhesion on the articular cartilage surface.

    Science.gov (United States)

    Lawrence, Alexandra; Xu, Xin; Bible, Melissa D; Calve, Sarah; Neu, Corey P; Panitch, Alyssa

    2015-12-01

    The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; decreased expression of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated type II collagen and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction, and adhesion, to control levels as assessed over macro-to micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury.

  15. Bringing research into a first semester organic chemistry laboratory with the multistep synthesis of carbohydrate-based HIV inhibitor mimics.

    Science.gov (United States)

    Pontrello, Jason K

    2015-01-01

    Benefits of incorporating research experiences into laboratory courses have been well documented, yet examples of research projects designed for the first semester introductory organic chemistry lab course are extremely rare. To address this deficiency, a Carbohydrate-Based human immunodeficiency virus (HIV) Inhibitor project consisting of a synthetic scheme of four reactions was developed for and implemented in the first semester organic lab. Students carried out the synthetic reactions during the last 6 of 10 total labs in the course, generating carbohydrate-based dimeric target molecules modeled after published dimers with application in HIV therapy. The project was designed to provide a research experience through use of literature procedures for reactions performed, exploration of variation in linker length in the target structure, and synthesis of compounds not previously reported in the scientific literature. Project assessment revealed strong student support, indicating enhanced engagement and interest in the course as a direct result of the use of scientific literature and the applications of the synthesized carbohydrate-based molecules. Regardless of discussed challenges in designing a research project for the first semester lab course, the finding from data analysis that a project implemented in the first semester lab had significantly greater student impact than a second semester project should provide motivation for development of additional research projects for a first semester organic course. © 2015 The International Union of Biochemistry and Molecular Biology.

  16. Synthesis, characterization and application of iron (II, III) oxide (Fe3O4) magnetic nanoparticles in mimic of wound healing model

    Science.gov (United States)

    Konyala, Divya

    The research study focused on synthesis, characterization and applications of Fe3O4 core-shelled magnetic nanomaterials. This Fe3O4 magnetic nanomaterials will be prepared by using cost effective and convenient wet-chemistry method and will encapsulated using aqueous extracts of medicinal natural products. Three natural products namely Symplocos racemosa, Picrorhiza kurroa and Butea monosperma used to encapsulate Fe3O 4 MNMs due to their scope to reduce the risk of cancer, improves health, increase energy and enhance the immunity. These three medicinal natural products are synthesize by using water as a solvents to derive its active constituents, which will further used to functionalize the magnetic nanomaterials. The magnetic nanoparticles characterization studies performed using X-ray powder diffraction, Scanning electron microscope, Transmission electron microscope, Ultraviolet-visible spectroscopy, Fourier Transform Infrared spectroscopy (FT-IR) and Magnetic property. Fe3O4 magnetic nanomaterials biological activity was tested on Gram-negative bacteria (Escherichia coli). The results pointed out that, due to the adequate coating of Fe 3O4 (Iron Oxide) core by the medicinal chemical constituents from the natural products, the absorption of Fe3O4 magnetic nanomaterials was not detected in the UV-VIS Spectroscopy. TEM images showed that Fe3O4 coated with natural product extract in core-shelled structure, and the size of the particle ranges from 6 nm to 10 nm. Fourier Transform Infrared spectroscopy (FT-IR) was performed to determine the nature of chemicals present in natural extracts and functionalized Fe3O 4 magnetic nanomaterials. The model of wound healing mimic and antibacterial activity performed on gram-negative (Escherichia coli), indicating steady increasing cell growth after adding Fe3O4 MNMs. It was also found that MNMs synthesized at high temperatures shows less wound healing activity, when compared to MNMs prepared at room temperature due to formation

  17. Synthesis, spectroscopic characterisation, DNA cleavage, superoxidase dismutase activity and antibacterial properties of some transition metal complexes of a novel bidentate Schiff base derived from isatin and 2-aminopyrimidine

    Science.gov (United States)

    Nitha, L. P.; Aswathy, R.; Mathews, Niecy Elsa; Sindhu kumari, B.; Mohanan, K.

    2014-01-01

    Complexes of manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II) with a Schiff base, formed by the condensation of isatin with 2-aminopyrimidine have been synthesised and characterised through elemental analysis, molar conductance measurements, magnetic susceptibility, IR, UV-Vis, 1HNMR, FAB mass and EPR spectral studies. The spectral data revealed that the ligand acts as neutral bidentate, coordinating to the metal ion through the carbonyl oxygen and azomethine nitrogen. Molar conductance values adequately support the electrolytic nature of the complexes. On the basis of the above observations the complexes have been formulated as [M(ISAP)2]X2, where M = Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); X = Cl, OAc; ISAP = 2-[N-indole-2-one]aminopyrimidine. The ligand and copper(II) complex were subjected to X-ray diffraction studies. The DNA cleavage study was monitored by gel electrophoresis method. The superoxide dismutase (SOD) mimetic activities of the ligand and the metal complexes were checked using NBT assay. The in vitro antibacterial activity of the synthesized compounds has been tested against gram negative and gram positive bacteria.

  18. Synthesis, spectroscopic characterisation, DNA cleavage, superoxidase dismutase activity and antibacterial properties of some transition metal complexes of a novel bidentate Schiff base derived from isatin and 2-aminopyrimidine.

    Science.gov (United States)

    Nitha, L P; Aswathy, R; Mathews, Niecy Elsa; Kumari, B Sindhu; Mohanan, K

    2014-01-24

    Complexes of manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II) with a Schiff base, formed by the condensation of isatin with 2-aminopyrimidine have been synthesised and characterised through elemental analysis, molar conductance measurements, magnetic susceptibility, IR, UV-Vis, (1)HNMR, FAB mass and EPR spectral studies. The spectral data revealed that the ligand acts as neutral bidentate, coordinating to the metal ion through the carbonyl oxygen and azomethine nitrogen. Molar conductance values adequately support the electrolytic nature of the complexes. On the basis of the above observations the complexes have been formulated as [M(ISAP)2]X2, where M=Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); X=Cl, OAc; ISAP=2-[N-indole-2-one]aminopyrimidine. The ligand and copper(II) complex were subjected to X-ray diffraction studies. The DNA cleavage study was monitored by gel electrophoresis method. The superoxide dismutase (SOD) mimetic activities of the ligand and the metal complexes were checked using NBT assay. The in vitro antibacterial activity of the synthesized compounds has been tested against gram negative and gram positive bacteria.

  19. Carbocyclic Carbohydrate Mimics as Potential Glycosidase Inhibitors

    DEFF Research Database (Denmark)

    Fanefjord, Mette; Lundt, Inge

    functionalities was introduced by either epoxidation or dihydroxylation of 7. Finally, reduction of the lactone ring led to the sugar mimics 8. The synthesis of several isomers of 8 will be presented. [1] a) Kleban, M. ; Hilgers, P. ; Greul, J.N. ; Kugler, R.D. ; Li, J. ; Picasso, S. ; Vogel, P. ; Jäger, V. Chem...

  20. Synthetic mimics of antimicrobial peptides--a versatile ring-opening metathesis polymerization based platform for the synthesis of selective antibacterial and cell-penetrating polymers.

    Science.gov (United States)

    Lienkamp, Karen; Tew, Gregory N

    2009-11-09

    Natural macromolecules exhibit an extensive arsenal of properties, many of which have proven difficult to recapitulate in simpler synthetic systems. Over the last couple of years, foldamers have emerged as one important step toward increased functionality in synthetic systems. While the great majority of work in this area has focused on folded structures, hence the name, more recent progress has centered on polymers that mimic protein function. These efforts have resulted in the design of relatively simple macromolecules; one example are the synthetic mimics of antimicrobial peptides (SMAMPs) that capture the central physicochemical features of their natural archetypes irrespective of the specific folded form. Here we present our recent efforts to create polymers which display biological activity similar to natural proteins, including antimicrobial and cell-penetrating peptides.

  1. Design, synthesis, and characterization of a 39 amino acid peptide mimic of the main immunogenic region of the Torpedo acetylcholine receptor.

    Science.gov (United States)

    Trinh, Vu B; Foster, Alex J; Fairclough, Robert H

    2014-05-01

    We have designed a 39 amino acid peptide mimic of the conformation-dependent main immunogenic region (MIR) of the Torpedo acetylcholine receptor (TAChR) that joins three discontinuous segments of the Torpedo α-subunit, α(1-12), α(65-79), and α(110 - 115) with two GS linkers: This 39MIR-mimic was expressed in E. coli as a fusion protein with an intein-chitin-binding domain (IChBD) to permit affinity collection on chitin beads. Six MIR-directed monoclonal antibodies (mAbs) bind to this complex and five agonist/antagonist site directed mAbs do not. The complex of MIR-directed mAb-132A with 39MIR has a Kd of (2.11±0.11)×10(-10)M, which is smaller than (7.13±1.20)×10(-10)M for the complex of mAb-132A with α(1-161) and about the same as 3.4×10(-10)M for that of mAb-132A with TAChR. Additionally, the 39MIR-IChBD adsorbs all MIR-directed antibodies (Abs) from an experimental autoimmune myasthenia gravis (EAMG) rat serum. Hence, the 39MIR-mimic has the potential to inactivate or remove pathogenic Torpedo MIR-directed Abs from EAMG sera and to direct a magic bullet to the memory B-cells that produce those pathogenic Abs. The hope is to use this as a guide to produce a mimic of the human MIR on the way to an antigen specific therapeutic agent to treat MG.

  2. Conjugates of Superoxide Dismutase 1 with Amphiphilic Poly(2-oxazoline) Block Copolymers for Enhanced Brain Delivery: Synthesis, Characterization and Evaluation in Vitro and in Vivo

    KAUST Repository

    Tong, Jing

    2013-01-07

    Superoxide dismutase 1 (SOD1) efficiently catalyzes dismutation of superoxide, but its poor delivery to the target sites in the body, such as brain, hinders its use as a therapeutic agent for superoxide-associated disorders. Here to enhance the delivery of SOD1 across the blood-brain barrier (BBB) and in neurons the enzyme was conjugated with poly(2-oxazoline) (POx) block copolymers, P(MeOx-b-BuOx) or P(EtOx-b-BuOx), composed of (1) hydrophilic 2-methyl-2-oxazoline (MeOx) or 2-ethyl-2-oxazoline (EtOx) and (2) hydrophobic 2-butyl-2-oxazoline (BuOx) repeating units. The conjugates contained from 2 to 3 POx chains joining the protein amino groups via cleavable -(ss)- or noncleavable -(cc)- linkers at the BuOx block terminus. They retained 30% to 50% of initial SOD1 activity, were conformationally and thermally stable, and assembled in 8 or 20 nm aggregates in aqueous solution. They had little if any toxicity to CATH.a neurons and displayed enhanced uptake in these neurons as compared to native or PEGylated SOD1. Of the two conjugates, SOD1-(cc)-P(MeOx-b-BuOx) and SOD1-(cc)-P(EtOx-b-BuOx), compared, the latter was entering cells 4 to 7 times faster and at 6 h colocalized predominantly with endoplasmic reticulum (41 ± 3%) and mitochondria (21 ± 2%). Colocalization with endocytosis markers and pathway inhibition assays suggested that it was internalized through lipid raft/caveolae, also employed by the P(EtOx-b-BuOx) copolymer. The SOD activity in cell lysates and ability to attenuate angiotensin II (Ang II)-induced superoxide in live cells were increased for this conjugate compared to SOD1 and PEG-SOD1. Studies in mice showed that SOD1-POx had ca. 1.75 times longer half-life in blood than native SOD1 (28.4 vs 15.9 min) and after iv administration penetrated the BBB significantly faster than albumin to accumulate in brain parenchyma. The conjugate maintained high stability both in serum and in brain (77% vs 84% at 1 h postinjection). Its amount taken up by the brain

  3. Diastereoselective Pictet-Spengler approach for the synthesis of pyrrolo[3,2-e][1,4]diazepin-2-one peptide turn mimics.

    Science.gov (United States)

    Deaudelin, Philippe; Lubell, William D

    2008-07-03

    Sixteen pyrrolo[3,2- e][1,4]diazepin-2-ones 1 were synthesized in 4-5 steps and 5-48% overall yields from 4-oxoproline 8 by a route featuring a diastereoselective Pictet-Spengler reaction to close the seven-membered diazepinone ring. Crystallographic analysis of pyrrolo[3,2- e][1,4]diazepin-2-one 1b by X-ray diffraction demonstrated that the alpha-amino acid residue adopted dihedral angle geometry similar to an ideal gamma-turn, illustrating the potential for employing these novel heterocycles as peptide turn mimics.

  4. MIMIC en Robin Hood

    NARCIS (Netherlands)

    R.A. de Mooij (Ruud); A.L. Bovenberg (Lans); F. van der Ploeg (Ploeg)

    1994-01-01

    textabstractVerlaging van het belastingtarief in de eerste schijf, gefinancierd met verhoging van het tarief in de andere schijven, is in het MIMIC-model van het Centraal Planbureau goed voor de werkgelegenheid. Onlangs werd .in E5B betwijfeld of het CPB de gevolgen van zo'n 'Robin Hood'- beleid

  5. Bacteriocuprein superoxide dismutases in pseudomonads

    Energy Technology Data Exchange (ETDEWEB)

    Steinman, H.M.

    1985-06-01

    Two new instances of the rare bacteriocuprein form of superoxide dismutase have been discovered in Pseudomonas diminuta and P. maltophilia. Each species contains a manganese superoxide dismutase as well. Eight other strains of Pseudomonas and Xanthomonas spp. lacked bacteriocupreins and contained either a manganese or an iron superoxide dismutase. Native molecular weights and isoelectric points were determined for all these bacterial dismutases. A monospecific polyclonal antibody was prepared against the bacteriocuprein from Photobacterium leiognathi; it was not cross-reactive with the bacteriocuprein from either Pseudomonas strain. Bacteriocupreins have previously been identified in only two procaryotes, P. leiognathi and Caulobacter crescentus. The discovery of the Pseudomonas bacteriocupreins reveals a broader distribution, raising the possibility that bacteriocupreins are a continuous line of descent among procryotes and not isolated evolutionary occurrences, as previous data suggested.

  6. Facile synthesis of enzyme-embedded magnetic metal-organic frameworks as a reusable mimic multi-enzyme system: mimetic peroxidase properties and colorimetric sensor

    Science.gov (United States)

    Hou, Chen; Wang, Yang; Ding, Qinghua; Jiang, Long; Li, Ming; Zhu, Weiwei; Pan, Duo; Zhu, Hao; Liu, Mingzhu

    2015-11-01

    This work reports a facile and easily-achieved approach for enzyme immobilization by embedding glucose oxidase (GOx) in magnetic zeolitic imidazolate framework 8 (mZIF-8) via a de novo approach. As a demonstration of the power of such materials, the resulting GOx embedded mZIF-8 (mZIF-8@GOx) was utilized as a colorimetric sensor for rapid detection of glucose. This method was constructed on the basis of metal-organic frameworks (MOFs), which possessed very fascinating peroxidase-like properties, and the cascade reaction for the visual detection of glucose was combined into one step through the mZIF-8@GOx based mimic multi-enzyme system. After characterization by electron microscopy, X-ray diffraction, nitrogen sorption, fourier transform infrared spectroscopy and vibrating sample magnetometry, the as-prepared mZIF-8@GOx was confirmed with the robust core-shell structure, the monodisperse nanoparticle had an average diameter of about 200 nm and displayed superparamagnetism with a saturation magnetization value of 40.5 emu g-1, it also exhibited a large surface area of 396.10 m2 g-1. As a peroxidase mimic, mZIF-8 was verified to be highly stable and of low cost, and showed a strong affinity towards H2O2. Meanwhile, the mZIF-8 embedded GOx also exhibited improved activity, stability and greatly enhanced selectivity in glucose detection. Moreover, the mZIF-8@GOx had excellent recyclability with high activity (88.7% residual activity after 12 times reuse).This work reports a facile and easily-achieved approach for enzyme immobilization by embedding glucose oxidase (GOx) in magnetic zeolitic imidazolate framework 8 (mZIF-8) via a de novo approach. As a demonstration of the power of such materials, the resulting GOx embedded mZIF-8 (mZIF-8@GOx) was utilized as a colorimetric sensor for rapid detection of glucose. This method was constructed on the basis of metal-organic frameworks (MOFs), which possessed very fascinating peroxidase-like properties, and the cascade

  7. MIMIC en Robin Hood

    OpenAIRE

    Mooij, Ruud; Bovenberg, Lans; Ploeg, Ploeg

    1994-01-01

    textabstractVerlaging van het belastingtarief in de eerste schijf, gefinancierd met verhoging van het tarief in de andere schijven, is in het MIMIC-model van het Centraal Planbureau goed voor de werkgelegenheid. Onlangs werd .in E5B betwijfeld of het CPB de gevolgen van zo'n 'Robin Hood'- beleid goed weergeeft. Het is echter de vraag of de niet-kwantificeerbare effecten wel van zo 'n groot belang zijn.

  8. Antimicrobial activities of squalamine mimics.

    OpenAIRE

    1997-01-01

    We investigated the antimicrobial properties of compounds with structural features that were designed to mimic those of squalamine, an antibiotic isolated from the stomach of the dogfish shark. The mimics, like squalamine, are sterol-polyamine conjugates. Unlike squalamine, the mimics were simple to prepare, at high yield, from readily available starting materials. Several squalamine mimics showed activity against gram-negative rods, gram-positive cocci including methicillin-resistant Staphyl...

  9. Synthesis and biological evaluation of cis-restricted triazole/tetrazole mimics of combretastatin-benzothiazole hybrids as tubulin polymerization inhibitors and apoptosis inducers.

    Science.gov (United States)

    Subba Rao, A V; Swapna, Konderu; Shaik, Siddiq Pasha; Lakshma Nayak, V; Srinivasa Reddy, T; Sunkari, Satish; Shaik, Thokhir Basha; Bagul, Chandrakant; Kamal, Ahmed

    2017-02-01

    A series of colchicine site binding tubulin inhibitors were synthesized by the modification of the combretastatin pharmacophore. The ring B was replaced by the pharmacologically relevant benzothiazole scaffolds, and the cis configuration of the olefinic bond was restricted by the incorporation of a triazole and tetrazole rings which is envisaged by the structural resemblance to a tubulin inhibitor like combretastatin (CA-4). These compounds were evaluated for their antiproliferative activity on selected cancer cell lines and an insight in the structure activity relationship was developed. The most potent compounds (9a and 9b) demonstrated an antiproliferative effect comparable to that of CA-4. Mitotic cell cycle arrest in G2/M phase revealed the disruption of microtubule dynamics that was confirmed by tubulin polymerization assays and immunocytochemistry studies at the cellular level. Western blot analysis revealed that these compounds accumulate more tubulin in the soluble fraction. The colchicine competitive binding assay and the molecular docking studies suggested that the binding of these mimics at the colchicine site of the tubulin is similar to that of CA-4. Moreover, the triggering of apoptotic cell death after mitotic arrest was investigated by studying their effect by Hoechst staining, Annexin-V-FITC assay, mitochondrial membrane potential, ROS generation and caspase-3 activation.

  10. Design and synthesis of cis-restricted benzimidazole and benzothiazole mimics of combretastatin A-4 as antimitotic agents with apoptosis inducing ability.

    Science.gov (United States)

    Ashraf, Md; Shaik, Thokhir B; Malik, M Shaheer; Syed, Riyaz; Mallipeddi, Prema L; Vardhan, M V P S Vishnu; Kamal, Ahmed

    2016-09-15

    A series of colchicine site binding tubulin inhibitors were designed and synthesized by the modification of the combretastatin A-4 (CA4) pharmacophore. The ring B was replaced by the pharmacologically relevant benzimidazole or benzothiazole scaffolds, and the cis-configuration of the olefinic bond was restricted by the incorporation of a pyridine ring which is envisaged by the structural resemblance to a tubulin inhibitor like E7010. These compounds were evaluated for their antiproliferative activity on selected cancer cell lines and an insight in the structure activity relationship was developed. The most potent compounds (6c and 6l) demonstrated an antiproliferative effect comparable and superior to that of CA4 (GI50 up to 40nM). Mitotic cell cycle arrest in G2/M phase revealed the disruption of microtubule dynamics that was confirmed by tubulin polymerization assays and immunocytochemistry studies at the cellular level. The molecular docking studies suggested that the binding of these mimics at the colchicine site of the tubulin is similar to that of combretastatin A-4.

  11. Parasomnias and their mimics.

    Science.gov (United States)

    Malhotra, Raman K; Avidan, Alon Y

    2012-11-01

    Parasomnias are classified into nonrapid eye movement and rapid eye movement sleep parasomnias. It is important for the clinician to consider other parasomnia mimics that present to the sleep disorders clinic. These conditions can be differentiated by taking a detailed sleep history and conducting nocturnal polysomnograms to evaluate for potential comorbidities and better characterize the disorder. Mainstays of treatment include treating any underlying primary sleep disorders that induce sleep fragmentation and could trigger the parasomnia, as well as implementing safety precautions to protect patients and their household. Pharmacologic treatment of many parasomnias is also available if needed and clinically indicated.

  12. 联二萘酚类磷酸吡哆醛模拟酶的合成与应用研究进展%Progress in Synthesis and Application of Binaphthol Type Pyridoxal Phosphate Mimic Enzyme

    Institute of Scientific and Technical Information of China (English)

    汤立军; 魏恭繁; 王楠楠

    2012-01-01

    Study on synthesis and application of artificial enzyme has important theoretical and applicable significance.Some recently studied binaphthol type pyridoxal phosphate mimic enzymes bearing the function of amino acid chiral conversion can be applied to enantioselective recognition of chiral 1,2-amino alcohols.Their synthesis and the application in chiral conversion of amino acids,enantioselective recognition of chiral 1,2-amino alcohols and extractive separation of amino acids as well as 1,2-amino alcohols were reviewed in this paper.%模拟酶化合物的合成与应用研究具有重要的理论和实际意义。近年来研究的一些联二萘酚类磷酸吡哆醛模拟酶具有氨基酸构型转换的功能,并可用于手性氨基醇的对映选择性识别。本文简要介绍了该类化合物的合成方法,综述了近年来联二萘酚类磷酸吡哆醛模拟酶在手性氨基酸构型转换、手性氨基醇对映选择性识别以及萃取拆分等方面的应用。

  13. Copper complexes of bioactive ligands with superoxide dismutase activity.

    Science.gov (United States)

    Khalid, Huma; Hanif, Muhammad; Hashmi, Muhammad Ali; Mahmood, Tariq; Ayub, Khurshid; Monim-Ul-Mehboob, Muhammad

    2013-11-01

    Free radicals or reactive oxygen species (ROS) are highly toxic and their damaging effects result in a variety of detrimental health issues such as neurodegenerative, cardiovascular and age-related diseases. Human body has evolved an effective defense system including superoxide dismutase (SOD) and catalase against the toxicity of these free radicals. SOD is a metalloenzyme and it acts as an excellent antioxidant to protect the body from superoxide radicals that are generated in the biological system. However, the clinical use of SOD is limited due to its short in vivo life span, and its large size that hampered its penetration across the cell membranes. Pharmaceuticals that provide ROS scavenging systems are the most effective when the production of ROS exceeds the scavenging capacity of endogenous SOD as a result of aging or pathological processes. Inspired by the Nature, scientists have designed metal-based mimics of the superoxide dismutase. This review focuses on different copper complexes that are developed from bioactive ligands and mimic the protecting action of the SOD.

  14. Antimicrobial activities of squalamine mimics.

    Science.gov (United States)

    Kikuchi, K; Bernard, E M; Sadownik, A; Regen, S L; Armstrong, D

    1997-07-01

    We investigated the antimicrobial properties of compounds with structural features that were designed to mimic those of squalamine, an antibiotic isolated from the stomach of the dogfish shark. The mimics, like squalamine, are sterol-polyamine conjugates. Unlike squalamine, the mimics were simple to prepare, at high yield, from readily available starting materials. Several squalamine mimics showed activity against gram-negative rods, gram-positive cocci including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and fungi. Some had little or no hemolytic activity. The hydrophobicity of the sterol backbone and the length and the cationic charge of the side chains appeared to be critical determinants of activity. One of the squalamine mimics, SM-7, was bactericidal against Escherichia coli, Pseudomonas aeruginosa, and S. aureus; its activity was decreased by divalent or monovalent cations and by bovine serum albumin. Subinhibitory concentrations of SM-7 markedly enhanced the antimicrobial activity of rifampin against gram-negative rods. These results suggest that the compounds may disrupt an outer membrane of gram-negative rods. Squalamine mimics are a new class of broad-spectrum antimicrobial agents. The antagonism of their activity by serum and albumin and their hemolytic properties may limit their use as systemic agents. The squalamine mimics, because of their potencies, broad spectra of antimicrobial activity, and potential for systemic toxicity, appear to be good candidates for development as topical antimicrobial agents.

  15. Synthesis of Triazole Bridged Vancomycin Mimics

    NARCIS (Netherlands)

    Zhang, J.

    2012-01-01

    Cyclic peptides are an important class of compounds with broad biological activities. Both natural as well as synthetic cyclic peptides have been recognized as a great resource and inspiration for drug discovery. Macrocyclization is recognized as an efficient way to restrict the conformational

  16. Synthesis of Triazole Bridged Vancomycin Mimics

    NARCIS (Netherlands)

    Zhang, J.

    2012-01-01

    Cyclic peptides are an important class of compounds with broad biological activities. Both natural as well as synthetic cyclic peptides have been recognized as a great resource and inspiration for drug discovery. Macrocyclization is recognized as an efficient way to restrict the conformational freed

  17. Synthesis of Triazole Bridged Vancomycin Mimics

    NARCIS (Netherlands)

    Zhang, J.|info:eu-repo/dai/nl/341589756

    2012-01-01

    Cyclic peptides are an important class of compounds with broad biological activities. Both natural as well as synthetic cyclic peptides have been recognized as a great resource and inspiration for drug discovery. Macrocyclization is recognized as an efficient way to restrict the conformational freed

  18. Manganese Superoxide Dismutase: Guardian of the Powerhouse

    Directory of Open Access Journals (Sweden)

    Daret K. St. Clair

    2011-10-01

    Full Text Available The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD acting as the chief ROS scavenging enzyme in the cell. Factors that affect the expression and/or the activity of MnSOD, resulting in diminished antioxidant capacity of the cell, can have extraordinary consequences on the overall health of the cell by altering mitochondrial metabolic function, leading to the development and progression of numerous diseases. A better understanding of the mechanisms by which MnSOD protects cells from the harmful effects of overproduction of ROS, in particular, the effects of ROS on mitochondrial metabolic enzymes, may contribute to the development of novel treatments for various diseases in which ROS are an important component.

  19. Superoxide dismutases in chronic gastritis.

    Science.gov (United States)

    Švagelj, Dražen; Terzić, Velimir; Dovhanj, Jasna; Švagelj, Marija; Cvrković, Mirta; Švagelj, Ivan

    2016-04-01

    Human gastric diseases have shown significant changes in the activity and expression of superoxide dismutase (SOD) isoforms. The aim of this study was to detect Mn-SOD activity and expression in the tissue of gastric mucosa, primarily in chronic gastritis (immunohistochemical Helicobacter pylori-negative gastritis, without other pathohistological changes) and to evaluate their possible connection with pathohistological diagnosis. We examined 51 consecutive outpatients undergoing endoscopy for upper gastrointestinal symptoms. Patients were classified based on their histopathological examinations and divided into three groups: 51 patients (archive samples between 2004-2009) with chronic immunohistochemical Helicobacter pylori-negative gastritis (mononuclear cells infiltration were graded as absent, moderate, severe) divided into three groups. Severity of gastritis was graded according to the updated Sydney system. Gastric tissue samples were used to determine the expression of Mn-SOD with anti-Mn-SOD Ab immunohistochemically. The Mn-SOD expression was more frequently present in specimens with severe and moderate inflammation of gastric mucosa than in those with normal mucosa. In patients with normal histological finding, positive immunoreactivity of Mn-SOD was not found. Our results determine the changes in Mn-SOD expression occurring in the normal gastric mucosa that had undergone changes in the intensity of chronic inflammatory infiltrates in the lamina propria. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  20. Versatile convergent synthesis of a three peptide loop containing protein mimic of whooping cough pertactin by successive Cu(I)-catalyzed azide alkyne cycloaddition on an orthogonal alkyne functionalized TAC-scaffold

    NARCIS (Netherlands)

    Werkhoven, Paul R; van de Langemheen, Helmus|info:eu-repo/dai/nl/341566667; van der Wal, Steffen|info:eu-repo/dai/nl/314571671; Kruijtzer, John A W|info:eu-repo/dai/nl/15207449X; Liskamp, Rob M J|info:eu-repo/dai/nl/069091315

    2014-01-01

    Synthetic mimics of discontinuous epitopes may have a wide range of potential applications, including synthetic vaccines and inhibition of protein-protein interactions. However, synthetic access to these relatively complex peptide molecular constructs is limited. This paper describes a versatile con

  1. Versatile convergent synthesis of a three peptide loop containing protein mimic of whooping cough pertactin by successive Cu(I)-catalyzed azide alkyne cycloaddition on an orthogonal alkyne functionalized TAC-scaffold

    NARCIS (Netherlands)

    Werkhoven, Paul R; van de Langemheen, Helmus; van der Wal, Steffen; Kruijtzer, John A W; Liskamp, Rob M J

    2014-01-01

    Synthetic mimics of discontinuous epitopes may have a wide range of potential applications, including synthetic vaccines and inhibition of protein-protein interactions. However, synthetic access to these relatively complex peptide molecular constructs is limited. This paper describes a versatile con

  2. A new mononuclear manganese(III) complex of an unsymmetrical hexadentate N3O3 ligand exhibiting superoxide dismutase and catalase-like activity: synthesis, characterization, properties and kinetics studies.

    Science.gov (United States)

    Ledesma, Gabriela N; Eury, Hélène; Anxolabéhère-Mallart, Elodie; Hureau, Christelle; Signorella, Sandra R

    2015-05-01

    A mononuclear Mn(III) complex MnL·4H2O (H3L=1-[N-(2-pyridylmethyl),N-(2-hydroxybenzyl)amino]-3-[N'-(2-hydroxybenzyl),N'-(4-methylbenzyl)amino]propan-2-ol) has been prepared and characterized. This complex catalyzes the dismutation of superoxide efficiently, with catalytic rate constant kcat=1.7×10(6)M(-1)s(-1) and IC50 1.26μM, obtained through the nitro blue tetrazolium photoreduction inhibition superoxide dismutase assay, in aqueous solution of pH7.8. MnL is also able to disproportionate more than 300 equivalents of H2O2 in CH3CN, with initial rate of H2O2 decomposition given by ri=kcat [MnL](2) [H2O2] and kcat=1.32(2)mM(-2)min(-1). The accessibility of the Mn(IV) state (E(p)=0.53V vs. saturated calomel electrode), suggests MnL employs a high-valent catalytic cycle to decompose O2(-) and H2O2. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Synthesis, crystal structures and spectroscopy of meclofenamic acid and its metal complexes with manganese(II), copper(II), zinc(II) and cadmium(II). Antiproliferative and superoxide dismutase activity.

    Science.gov (United States)

    Kovala-Demertzi, Dimitra; Staninska, Malgorzata; Garcia-Santos, Isabel; Castineiras, Alfonso; Demertzis, Mavroudis A

    2011-09-01

    Some new complexes of meclofenamic acid (N-(2,6-dichloro-m-tolyl)anthranilic acid), Hmeclo (1), with potentially interesting biological activities are described. Complexes [Mn(meclo)(2)] (2), [Cu(meclo)(2)(H(2)O)(2)] (3), [Zn(meclo)(2)(H(2)O)(2)] (4) and [Cd(meclo)(2)(H(2)O)(2)] (5) were prepared and structurally characterized by means of vibrational, electronic and (1)H and (13)C NMR spectroscopies. The crystal structure of complexes [Cu(4)(meclo)(6)(OH)(2)(DMSO)(2)]2DMSO (3a) and [Cd(meclo)(2)(DMSO)(3)] (5a) have been determined by X-ray crystallography. Complex (3a) is a centrosymmetric tetramer built up around the planar cyclic Cu(2)(OH)(2) unit. Complex 5a is mononuclear seven-coordinated complex with the meclofenamato ligand behaving as a bidentate deprotonated chelating ligand. Intra and intermolecular hydrogen bonds stabilize these two structures, while the crystal packing is determined by π-π and C-H--π interactions. Meclofenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), and A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. Complex 5 exhibits the highest selectivity against MCF-7 and 4 shows the highest selectivity against T-24. Complexes 2-5 were found to be more potent cytotoxic agents against T-24 and complex 5 against MCF-7 cancer cell lines than the prevalent benchmark metallodrug, cis-platin. The superoxide dismutase activity was measured by the Fridovich test which showed that complex [Cu(meclo)(2)(H(2)O)(2)] is a good superoxide scavenger.

  4. Manganese superoxide dismutase and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Christensen, Mariann; Lash, Timothy L

    2014-01-01

    BACKGROUND: Manganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast...

  5. Triazacyclophane (TAC)-scaffolded histidine and aspartic acid residues as mimics of non-heme metalloenzyme active sites

    NARCIS (Netherlands)

    Albada, H.B.; Soulimani, F.; Jacobs, H.J.F.; Versluis, C.; Weckhuysen, B.M.; Liskamp, R.M.J.

    2012-01-01

    We describe the synthesis and coordination behaviour to copper(II) of two close structural triazacyclophane-based mimics of two often encountered aspartic acid and histidine containing metalloenzyme active sites. Coordination of these mimics to copper(I) and their reaction with molecular oxygen lead

  6. One-pot synthesis of porphyrin functionalized γ-Fe{sub 2}O{sub 3} nanocomposites as peroxidase mimics for H{sub 2}O{sub 2} and glucose detection

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qingyun, E-mail: qyliu@sdust.edu.cn; Zhang, Leyou; Li, Hui; Jia, Qingyan; Jiang, Yanling; Yang, Yanting; Zhu, Renren

    2015-10-01

    Meso-tetrakis(4-carboxyphenyl)-porphyrin-functionalized γ-Fe{sub 2}O{sub 3} nanoparticles (H{sub 2}TCPP-γ-Fe{sub 2}O{sub 3}) were successfully prepared by one-pot method under hydrothermal conditions and were found to possess intrinsic peroxidase-like activity. The H{sub 2}TCPP-γ-Fe{sub 2}O{sub 3} nanocomposites can catalytically oxidize peroxidase substrate 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H{sub 2}O{sub 2} to produce a blue color reaction, which can be easily observed by the naked eye. Furthermore, kinetic studies indicate that the H{sub 2}TCPP-γ-Fe{sub 2}O{sub 3} nanocomposites have an even higher affinity to TMB than that of the natural enzyme, horseradish peroxidase (HRP). On the basis of the high activity, the reaction provides a simple, sensitive and selective method for colorimetric detection of H{sub 2}O{sub 2} over a range of 10–100 μM with a minimum detection limit of 1.73 μM. Moreover, H{sub 2}TCPP-γ-Fe{sub 2}O{sub 3}/glucose oxidase (GOx)/TMB system provides a novel colorimetric sensor for glucose and shows good response toward glucose detection over a range of 5–25 μM with a minimum detection limit of 2.54 μM. The results indicated that it is a simple, cheap, convenient, highly selective, sensitive and easy handling colorimetric assay. Results of a fluorescent probe suggest that the catalase-mimic activity of the H{sub 2}TCPP-γ-Fe{sub 2}O{sub 3} nanocomposites effectively catalyze the decomposition of H{sub 2}O{sub 2} into H{sub 2}O and O{sub 2}. - Graphical abstract: 5,10,15,20-Tetrakis(4-carboxyl phenyl)-porphyrin (H{sub 2}TCPP)-γ-Fe{sub 2}O{sub 3} nanocomposites were demonstrated to possess intrinsic peroxidase-like activity and showed a higher catalytic activity, compared to that of γ-Fe{sub 2}O{sub 3} nanoparticles alone. - Highlights: • Porphyrin-functionalized γ-Fe{sub 2}O{sub 3} nanoparticles were prepared by one-pot method. • The porphyrin-γ-Fe{sub 2}O{sub 3} nanocomposites were found to possess

  7. Synthesis of mimic molecularly imprinted ordered mesoporous silica adsorbent by thermally reversible semicovalent approach for pipette-tip solid-phase extraction-liquid chromatography fluorescence determination of estradiol in milk.

    Science.gov (United States)

    Wang, Lu; Yan, Hongyuan; Yang, Chunliu; Li, Zan; Qiao, Fengxia

    2016-07-22

    A mimic molecularly imprinted ordered mesoporous silica (MIOMS) adsorbent was prepared utilizing a thermally reversible semicovalent approach. The thermally reversible covalent template-monomer complex was firstly synthesized by employing 4,4'-sulfonyldiphenol (BPS) and (3-isocyanatopropyl) triethoxysilane (ICPTES) as template and monomer, respectively. The template-monomer complex was incorporated into ordered mesoporous silica via a simple self-assembly process. The adsorption experiment illustrated that the imprint-removed silica (MIOMS-ir) had higher special recognition ability (250μgg(-1)) for estradiol (E2) than the non-imprinted silica (NIOMS-ir) (25μgg(-1)). MIOMS-ir was applied as an adsorbent in pipette-tip solid-phase extraction (PT-SPE) coupled with liquid chromatography-fluorescence detector (LC-FLD) for determination of E2 in milk samples. Under the optimized conditions, only 3mg of the adsorbent, 0.3mL of water as washing solvent, and 0.5mL of acetonitrile-acetic acid (96:4, v/v) as elution solvent were used in the pretreatment procedure of milk samples. Good calibration linearity was obtained in a range of 25ngL(-1) to 1000ngL(-1), and the recoveries at three spiked levels were ranged from 95.4% to 107.0% with relative standard deviations (RSDs) ≤3.1% (n=3). The proposed MIOMS-ir-PT-SPE-LC-FLD method combined the advantages of PT-SPE and ordered mesoporous material such as ease assembly, low cost, high extraction efficiency and large specific surface area, so it is a potential pretreatment strategy for the extraction and determination of E2 in complex milk samples.

  8. Phase transfer synthesis of N,N'(1,2-phenylene)bis-hippuricamide tethered metal based functionalized nanoparticles: A study on some novel microbial targeting peptide-mimic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Raman, N., E-mail: drn_raman@yahoo.co.in [Research Department of Chemistry, VHNSN College, Virudhunagar 626 001 (India); Sudharsan, S. [Research Department of Chemistry, VHNSN College, Virudhunagar 626 001 (India)

    2011-10-01

    This paper presents the novel synthesis of peptide, N,N'(1,2-phenylene)bis-hippuricamide tethered metal [Cu(II), Zn(II), Ni(II) and Co(II)] based functionalized nanoparticles via modified Brust-Schiffrin methodology. The growth, organic composition and morphology of these functionalized nanoparticles have been evaluated by UV-Vis, FT-IR spectroscopy and scanning electron microscopy. They are structurally and thermally characterized by X-ray diffraction and thermogravimetric analysis. Moreover, the interfacial dealings of these functionalized nanoparticles with Calf-thymus DNA and pUC19 DNA reveal that the functionalized nanoparticles of cobalt is an effective DNA damaging agent under physiological conditions. This has been supported by its efficient antimicrobial character against few fungal and bacterial strains, thereby steering its way towards biomedical applications as a metal based nanocarrier.

  9. Extracellular superoxide dismutase of boar seminal plasma.

    Science.gov (United States)

    Kowalowka, M; Wysocki, P; Fraser, L; Strzezek, J

    2008-08-01

    Superoxide dismutase (SOD) is an enzymatic component of the antioxidant defense system that protects spermatozoa by catalysing the dismutation of superoxide anions to hydrogen peroxide and oxygen. Age and season effects on SOD activity in the seminal plasma were measured in boars at the onset of 8 months through a 35-month period. It was found that age-related changes in SOD activity in the seminal plasma were markedly higher in boars less than 2 years of age. However, it appeared that SOD activity was established at the early sexual maturity age (8-12 months). There were variations in SOD activity throughout the season, being significantly higher in spring and autumn than in summer. A secretory extracellular form of SOD (EC-SOD) was purified to homogeneity (350-fold) from boar seminal plasma, using a three-step purification protocol (affinity chromatography followed by ion exchange and ceramic hydroxyapatite chromatography). The molecular properties and specificity of SOD (molecular mass, isoelectric point, optimum pH, thermostability and susceptibility to inhibitors) confirmed that the purified enzyme is an extracellular form of Cu/Zn-superoxide dismutase occurring in boar seminal plasma. The results of this study indicate that EC-SOD is an important antioxidant enzyme of boar seminal plasma, which plays an important physiological role in counteracting oxidative stress in spermatozoa.

  10. Molecularly-imprinted polymers as synythetic mimics of bioreceptors. 2. Applications in modern biotechnology

    Directory of Open Access Journals (Sweden)

    Sergeyeva T. A.

    2009-12-01

    Full Text Available The review is devoted to the analysis of publications on the synthesis of artificial mimics of biological receptors as well as their application in biotechnology. The special attention is paid to such areas of biotechnology: sensor technology, solid-phase extraction, pseudoimmunoassay, and chromatography.

  11. Carbocyclic Carbohydrate Mimics as Potential Glycosidase Inhibitors

    DEFF Research Database (Denmark)

    Fanefjord, Mette; Lundt, Inge

    It has been proven that aminocyclopentanols having the aminogroup adjacent to a carbon sidechain could be potential anomer-selective glycosidase inhibitors [1]. A successful pathway for synthesising mimics to L-carbohydrates 2, by introducing nitrogen to the C6 position in compound 1, has been...... developed in our group. A similar strategy has been used for synthesising mimics of D-carbohydrates. The α,β-unsaturated lactone 3 was cyclised to compound 4 which was further transformed into 5. The nitrogen functionality in compound 7 is introduced by an Overman rearrangement of 6 and the hydroxyl...

  12. Carbonic anhydrase mimics for enhanced CO2 absorption in an amine-based capture solvent.

    Science.gov (United States)

    Kelsey, Rachael A; Miller, David A; Parkin, Sean R; Liu, Kun; Remias, Joe E; Yang, Yue; Lightstone, Felice C; Liu, Kunlei; Lippert, Cameron A; Odom, Susan A

    2016-01-07

    Two new small-molecule enzyme mimics of carbonic anhydrase were prepared and characterized. These complexes contain the salen-like ligand bis(hydroxyphenyl)phenanthroline. This ligand is similar to the salen-type ligands previously incorporated into carbonic anhydrase mimics but contains no hydrolyzable imine groups and therefore serves as a promising ligand scaffold for the synthesis of a more robust CO2 hydration catalyst. These homogeneous catalysts were investigated for CO2 hydration in concentrated primary amine solutions through which a dilute CO2 (14%) fluid stream was flowed and showed exceptional activity for increased CO2 absorption rates.

  13. A chemical system that mimics decoding operations.

    Science.gov (United States)

    Giansante, Carlo; Ceroni, Paola; Venturi, Margherita; Sakamoto, Junji; Schlüter, A Dieter

    2009-02-23

    The chemical information stored in equilibrium mixtures of molecular species is larger than the sum of information carried by the individual molecules. Protonation equilibria in dilute dichloromethane solution of a shape-persistent macrocycle bearing two 2,2'-bipyridine units and two Coumarin 2 moieties (see figure) can be exploited to mimic decoding operations.

  14. Permanent female mimics in a lekking shorebird

    NARCIS (Netherlands)

    Jukema, Joop; Piersma, Theunis

    2006-01-01

    Female mimics are known from many species, but permanent, non-conditional, alternative mating strategies are only known from an isopod, a fish, a lizard and a bird. The single bird example refers to lek-breeding ruffs Philomachus pugnax, a shorebird for which two strategies (independent and satellit

  15. Bovine Serum Albumin Metal Complexes for Mimic of SOD

    Indian Academy of Sciences (India)

    GUIFANG YAN; YUFENG HE; GANG LI; YUBING XIONG; PENGFEI SONG; RONG-MIN WANG

    2016-11-01

    Superoxide anion radical (O•−₂ ) is a noxious reactive oxygen species (ROS). Transition metal ion complexes have been generally used as antioxidants to eliminate ROS. In this work, a neoteric watersoluble biopolymer metal complex (BSA-M) was prepared by conjugating the soluble biopolymer bovineserum albumin (BSA) with three transition metal ions (M, M=Cu, Co, Mn). The binding mode and ratio of metal ions bound to albumin were investigated. The BSA-M complexes were characterized by UV-Vis, circular dichroism (CD) spectra and polyacrylamide gel electrophoresis (PAGE). BSA served as polymerscaffold and the metal complex functioned as the catalytic active center. The results demonstrated that the structure of BSA remained unchanged when the binding ratio of transition metal ion complex to BSA was 5:1. Furthermore, the scavenging superoxide anion free radical (O•−₂ ) activity of biopolymer-metal complexes were determined by nitroblue tetrazolium light reduction assay method. The antioxidant capacity of BSA-M has markedly increased. The conjugated BSA-M (M=Cu, Mn) showed preeminent scavenging activity for O•−₂ , and the EC₅₀ value of the BSA-Cu was 0.038±0.0013μmol·L⁻¹, which is comparable to EC₅₀ value (0.041±0.001μmol·L⁻¹) of the natural superoxide dismutase (SOD), the analog quantity reached 107%. As a consequence, it can be considered as a bio-functional mimic of enzyme SOD and has a promising application prospect in antioxidant drug field.

  16. Mimics and chameleons in motor neurone disease.

    Science.gov (United States)

    Turner, Martin R; Talbot, Kevin

    2013-06-01

    The progression of motor neurone disease (MND) is currently irreversible, and the grave implications of diagnosis naturally fuels concern among neurologists over missing a potential mimic disorder. There is no diagnostic test for MND but in reality there are few plausible mimics in routine clinical practice. In the presence of a progressive pure motor disorder, signs such as florid fasciculations, bilateral tongue wasting, the 'split hand', head drop, emotionality, and cognitive or behavioural impairment carry high positive predictive value. MND is clinically heterogeneous, however, with some important chameleon-like presentations and considerable variation in clinical course. Lack of confidence about the scope of such variation, or an approach to diagnosis emphasising investigations over clinical common sense, has the potential to exacerbate diagnostic delay in MND and impede timely planning of the care which is essential to maximising quality of life.

  17. Role of extracellular superoxide dismutase in hypertension.

    Science.gov (United States)

    Gongora, Maria Carolina; Qin, Zhenyu; Laude, Karine; Kim, Ha Won; McCann, Louise; Folz, J Rodney; Dikalov, Sergey; Fukai, Tohru; Harrison, David G

    2006-09-01

    We previously found that angiotensin II-induced hypertension increases vascular extracellular superoxide dismutase (ecSOD), and proposed that this is a compensatory mechanism that blunts the hypertensive response and preserves endothelium-dependent vasodilatation. To test this hypothesis, we studied ecSOD-deficient mice. ecSOD(-/-) and C57Blk/6 mice had similar blood pressure at baseline; however, the hypertension caused by angiotensin II was greater in ecSOD(-/-) compared with wild-type mice (168 versus 147 mm Hg, respectively; P<0.01). In keeping with this, angiotensin II increased superoxide and reduced endothelium-dependent vasodilatation in small mesenteric arterioles to a greater extent in ecSOD(-/-) than in wild-type mice. In contrast to these findings in resistance vessels, angiotensin II paradoxically improved endothelium-dependent vasodilatation, reduced intracellular and extracellular superoxide, and increased NO production in aortas of ecSOD(-/-) mice. Whereas aortic expression of endothelial NO synthase, Cu/ZnSOD, and MnSOD were not altered in ecSOD(-/-) mice, the activity of Cu/ZnSOD was increased by 80% after angiotensin II infusion. This was associated with a concomitant increase in expression of the copper chaperone for Cu/ZnSOD in the aorta but not in the mesenteric arteries. Moreover, the angiotensin II-induced increase in aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity was diminished in ecSOD(-/-) mice as compared with controls. Thus, during angiotensin II infusion, ecSOD reduces hypertension, minimizes vascular superoxide production, and preserves endothelial function in resistance arterioles. We also identified novel compensatory mechanisms involving upregulation of copper chaperone for Cu/ZnSOD, increased Cu/ZnSOD activity, and decreased reduced nicotinamide-adenine dinucleotide phosphate oxidase activity in larger vessels. These compensatory mechanisms preserve large vessel function when ecSOD is absent in

  18. Engineering hydrogels as extracellular matrix mimics

    OpenAIRE

    Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun; Demirci, Utkan

    2010-01-01

    Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell–cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable....

  19. Synthesis of conformationally restricted beta-turn mimics

    NARCIS (Netherlands)

    IJsselstijn, Maarten

    2006-01-01

    This thesis aims at developing methods for introducing conformational restriction in Beta-turns, the turn elements present in Beta-sheets. A conformationally restricted peptide might either be formed via incorporation of a bridging diamino acids in a growing peptide chain, or via covalent bond formi

  20. Rationally designed squaryldiamides - a novel class of sugar-nucleotide mimics?

    Science.gov (United States)

    Niewiadomski, Sven; Beebeejaun, Zeenat; Denton, Helen; Smith, Terry K; Morris, Richard J; Wagner, Gerd K

    2010-08-07

    Sugar-nucleotides such as GDP-mannose, GDP-fucose and UDP-glucose are important biomolecules with a central role in carbohydrate and glycoconjugate biosynthesis, metabolism and cell signalling. Analogues and mimics of naturally occurring sugar-nucleotides are sought after as chemical tools and inhibitor candidates for sugar-nucleotide-dependent enzymes including glycosyltransferases. Many sugar-nucleotides bind to their target glycosyltransferases via coordination of the diphosphate group to a divalent metal cofactor in the active site. The identification of uncharged, chemically stable surrogates for the diphosphate group, with the ability to coordinate to a divalent metal, is therefore an important design criteria for the development of sugar-nucleotide mimics. Here, we describe the rational design and synthesis of a novel class of sugar-nucleotide mimics based on a squaryldiamide scaffold, an uncharged phosphate isostere. We demonstrate by comprehensive NMR titration experiments that the new sugar-nucleotide mimics coordinate efficiently to Mg(2+), and provide results from biological studies with a therapeutically relevant mannosyltransferase from Trypanosoma brucei. Our findings suggest that squaryldiamides are a promising template for the development of sugar-nucleotide mimics, and illustrate the considerable potential of the squarylamide group as a fragment for inhibitor design.

  1. A bioconjugate approach toward squalamine mimics: Insight into the mechanism of biological action.

    Science.gov (United States)

    Chen, Wen-Hua; Shao, Xue-Bin; Moellering, Robert; Wennersten, Christine; Regen, Steven L

    2006-01-01

    A short and efficient synthesis has been devised for a family of squalamine mimics, based on the use of cholic acid, deoxycholic acid, lithocholic acid, putrescine, and spermine as starting materials. Those mimics that contain two facially amphiphilic sterol-spermidine conjugates show strong antibacterial activity against a broad spectrum of Gram-positive bacteria; their corresponding activities against a broad spectrum of Gram-negative bacteria are relatively moderate. Larger mimics, containing four such sterol-spermidine conjugates, exhibit very weak activities. Reversal of the pendent spermidine moiety and a putrescine linkage on the A- and D-rings had little consequence on the antibacterial activity for the most active of the squalamine mimics, which contained two sterol-polyamine units; similar results were obtained with squalamine mimics made from only one sterol unit. Detailed structure-activity measurements, in combination with kinetic studies carried out using liposomes as model membranes, support a mechanism of action involving noncovalent dimers as ion transporting species, most probably via the formation of pores or channels.

  2. Combinatorial Chemistry of Piperidine Based Carbohydrate Mimics

    DEFF Research Database (Denmark)

    Byrgesen, Elisabeth Vang; Nielsen, John; Willart, Marianne

    1997-01-01

    Piperidine carboxylic acids and 4-hydroxypiperidine-3-carboxylic acid, the latter obtained from bakers yeast reduction of the corresponding piperidone, were coupled in solid-phase synthesis to form simplified oligosaccharide analogues. A split-and-mix synthesis approach was used to create small c...

  3. Combinatorial Chemistry of Piperidine Based Carbohydrate Mimics

    DEFF Research Database (Denmark)

    Byrgesen, Elisabeth Vang; Nielsen, John; Willart, Marianne

    1997-01-01

    Piperidine carboxylic acids and 4-hydroxypiperidine-3-carboxylic acid, the latter obtained from bakers yeast reduction of the corresponding piperidone, were coupled in solid-phase synthesis to form simplified oligosaccharide analogues. A split-and-mix synthesis approach was used to create small c...

  4. Oxidative stress and superoxide dismutase activity in brain of rats ...

    African Journals Online (AJOL)

    JTEkanem

    effect of superoxide dismutase (SOD) activity in brain homogenates of Wistar rats. Oxidative stress measured as ... SOD is an important enzyme family in living cells for maintaining ..... one unit of activity with oxidation rate of organic substrate in.

  5. Recognition of extended linear and cyclised polyketide mimics by a Type II acyl carrier protein

    OpenAIRE

    Dong, Xu; Bailey, Christopher; Williams, Christopher; Crosby, John; Simpson, Tom; Willis, Chris; Crump, Matthew

    2016-01-01

    Polyketides are secondary metabolites which display both valuable pharmaceutical and agrochemical properties. Biosynthesis is performed by polyketide synthases (PKSs), and the acyl carrier protein (ACP), a small acidic protein, that transports the growing polyketide chain and is essential for activity. Here we report the synthesis of two aromatic probes and a linear octaketide mimic that have been tethered to actinorhodin ACP. These experiments were aimed at probing the ACP’s capacity to sequ...

  6. Molecularly imprinted polymers as synthetic mimics of bioreceptors. 1. General principles of molecular imprinting

    Directory of Open Access Journals (Sweden)

    Sergeyeva T. A.

    2009-08-01

    Full Text Available The review is devoted to analysis of the publications in the area of synthesis of artificial mimics of biological receptors using the method of molecular imprinting. General principles of molecular imprinting as well as main types of polymers being used in molecular imprinting are described. The special attention is paid to the polymers-biomimics synthesized using the method of non-covalent molecular imprinting.

  7. Molecularly imprinted polymers as synthetic mimics of bioreceptors. 1. General principles of molecular imprinting

    OpenAIRE

    Sergeyeva T. A.

    2009-01-01

    The review is devoted to analysis of the publications in the area of synthesis of artificial mimics of biological receptors using the method of molecular imprinting. General principles of molecular imprinting as well as main types of polymers being used in molecular imprinting are described. The special attention is paid to the polymers-biomimics synthesized using the method of non-covalent molecular imprinting.

  8. Can strange stars mimic dark energy stars?

    CERN Document Server

    Deb, Debabrata; Guha, B K; Ray, Saibal

    2016-01-01

    The possibility of strange stars mixed with dark energy to be one of candidates for dark energy stars is the main issue of the present study. Our investigation shows that quark matter is acting as dark energy after certain yet unknown critical condition inside the quark stars. Our proposed model reveals that strange stars mixed with dark energy feature not only a physically acceptable stable model but also mimic characteristics of dark energy stars. The plausible connections are shown through the mass-radius relation as well as the entropy and temperature. We particulary note that two-fluid distribution is the major reason for anisotropic nature of the spherical stellar system.

  9. Oxidoreductase mimic activity of natural pyrrhotite

    Science.gov (United States)

    Ibáñez de Aldecoa, A. L.; Velasco, F.; Menor-Salván, C.

    2012-09-01

    The theory of the chemo-autotrophic origin of life, also called the "iron-sulfur world hypothesis", proposes that the system FeS/FeS2 present in the primitive Earth crust gave the reductive power necessary to conduct the first protometabolic redox reactions. Some experimental studies demonstrated the redox activity of the FeS/SH2 system, but none of them used natural FeS. Here, we show that the iron sulfide mineral pyrrhotite is able to mimic the redox activity of the enzyme lactate dehydrogenase, which reversibly reduces the pyruvate in lactate, under prebiotic conditions with pyrite formation.

  10. Meningeal fibroma: a rare meningioma mimic.

    Science.gov (United States)

    Kakkar, Aanchal; Sharma, Mehar C; Goyal, Nishant; Sarkar, Chitra; Suri, Vaishali; Garg, Ajay; Kale, Shashank S; Suri, Ashish

    2014-08-01

    Meningeal fibromas are rare intracranial tumors that mimic meningiomas radiologically as well as histologically. The authors report 2 cases of meningeal fibroma with detailed clinical, radiological, histopathological, and immunohistochemical features, and discuss the differential diagnosis of this entity. Knowledge of this rare tumor is essential for pathologists to be able distinguish it from more common meningeal tumors, especially in younger patients. This knowledge is also essential for neurosurgeons, as incomplete resection may lead to tumor recurrence, and such patients require close follow-up.

  11. Do benzodiazepines mimic reverse-turn structures?

    Science.gov (United States)

    Hata, Masayuki; Marshall, Garland R.

    2006-05-01

    The role of benzodiazepine derivatives (BZD) as a privileged scaffold that mimics β-turn structures (Ripka et al. (1993) Tetrahedron 49:3593-3608) in peptide/protein recognition was reexamined in detail. Stable BZD ring conformers were determined with MM3, and experimental reverse-turn structures were extracted from the basis set of protein crystal structures previously defined by Ripka et al. Ideal β-turns were also modeled and similarly compared with BZD conformers. Huge numbers of conformers were generated by systematically scanning the torsional degrees of freedom for BZDs, as well as those of ideal β-turns for comparison. Using these structures, conformers of BZDs were fit to experimental structures as suggested by Ripka et al., or modeled classical β-turn conformers, and the root-mean-square deviation (RMSD) values were calculated for each pairwise comparison. Pairs of conformers with the smallest RMSD values for overlap of the four α-β side-chain orientations were selected. All overlaps of BZD conformers with experimental β-turns yielded one or more comparisons where the least RMSD was significantly small, 0.48-0.86 Å, as previously suggested. Utilizing a different methodology, the overall conclusion that benzodiazepines could serve as reverse-turn mimetics of Ripka et al. is justified. The least RMSD values for the overlap of BZDs and modeled classical β-turns were also less than 1 Å. When comparing BZDs with experimental or classical β-turns, the set of experimental β-turns selected by Ripka et al. fit the BZD scaffolds better than modeled classical β-turns; however, all the experimental β-turns did not fit a particular BZD scaffold better. A single BZD ring conformation, and/or chiral orientation, can mimic some, but not all, of the experimental β-turn structures. BZD has two central ring conformations and one chiral center that explains why the four variations of the BZD scaffold can mimic all types of β-turn structure examined. It was

  12. Right-sided diverticulitis mimics appendicitis.

    Science.gov (United States)

    Gilmore, Thomas; Jordan, Charlton; Edelstein, Elisabeth

    2013-01-01

    Right-sided diverticulitis is a rare source of right lower quadrant pain in Western society; however, it is quite common in Asian societies. Right-sided diverticulitis presents very similarly to appendicitis, with right lower quadrant pain, fever, nausea, and laboratory abnormalities, and is often seen in young patients. In this report, we present a case of right-sided diverticulitis. We review right-sided diverticulitis' diagnosis and management. It is important to diagnose right-sided diverticulitis because it is a good mimic of appendicitis and ideally should be diagnosed before a patient has unnecessary surgery. A 26-year-old Asian woman presented for evaluation of right lower quadrant pain and fever. She was initially thought to have appendicitis clinically, but had right-sided diverticulitis diagnosed by computed tomography (CT) scan. She was admitted and received intravenous antibiotics and bowel rest. Her right-sided diverticulitis resolved in 3 days. Severe right lower quadrant pain in young patients of Asian descent can be right-sided diverticulitis. Right-sided diverticulitis is a benign condition managed medically that mimics appendicitis. CT imaging seems to be the best way to avoid unnecessary surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Engineering hydrogels as extracellular matrix mimics.

    Science.gov (United States)

    Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun; Demirci, Utkan

    2010-04-01

    Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell-cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine.

  14. Preparation of highly efficient manganese catalase mimics.

    Science.gov (United States)

    Triller, Michael U; Hsieh, Wen-Yuan; Pecoraro, Vincent L; Rompel, Annette; Krebs, Bernt

    2002-10-21

    The series of compounds [Mn(bpia)(mu-OAc)](2)(ClO(4))(2) (1), [Mn(2)(bpia)(2)(muO)(mu-OAc)](ClO(4))(3).CH(3)CN (2), [Mn(bpia)(mu-O)](2)(ClO(4))(2)(PF(6)).2CH(3)CN (3), [Mn(bpia)(Cl)(2)](ClO)(4) (4), and [(Mn(bpia)(Cl))(2)(mu-O)](ClO(4))(2).2CH(3)CN (5) (bpia = bis(picolyl)(N-methylimidazol-2-yl)amine) represents a structural, spectroscopic, and functional model system for manganese catalases. Compounds 3 and 5 have been synthesized from 2 via bulk electrolysis and ligand exchange, respectively. All complexes have been structurally characterized by X-ray crystallography and by UV-vis and EPR spectroscopies. The different bridging ligands including the rare mono-mu-oxo and mono-mu-oxo-mono-mu-carboxylato motifs lead to a variation of the Mn-Mn separation across the four binuclear compounds of 1.50 A (Mn(2)(II,II) = 4.128 A, Mn(2)(III,III) = 3.5326 and 3.2533 A, Mn(2)(III,IV) = 2.624 A). Complexes 1, 2, and 3 are mimics for the Mn(2)(II,II), the Mn(2)(III,III), and the Mn(2)(III,IV) oxidation states of the native enzyme. UV-vis spectra of these compounds show similarities to those of the corresponding oxidation states of manganese catalase from Thermus thermophilus and Lactobacillus plantarum. Compound 2 exhibits a rare example of a Jahn-Teller compression. While complexes 1 and 3 are efficient catalysts for the disproportionation of hydrogen peroxide and contain an N(4)O(2) donor set, 4 and 5 show no catalase activity. These complexes have an N(4)Cl(2) and N(4)OCl donor set, respectively, and serve as mimics for halide inhibited manganese catalases. Cyclovoltammetric data show that the substitution of oxygen donor atoms with chloride causes a shift of redox potentials to more positive values. To our knowledge, complex 1 is the most efficient binuclear functional manganese catalase mimic exhibiting saturation kinetics to date.

  15. Superoxide dismutase phenotypes in duodenal ulcers: A genetic marker?

    Directory of Open Access Journals (Sweden)

    Sulekha S

    2006-01-01

    Full Text Available Background:Cu-Zn superoxide dismutases are antioxidative defensive enzymes that catalyze the reduction of superoxide anions to hydrogen peroxide. Aim:The study focuses on the association of electromorph of superoxide dismutase with duodenal ulcers, which result due to an imbalance between aggressive and defensive factors. Materials and Methods:Endoscopically confirmed 210 duodenal ulcer patients and 185 healthy individuals for comparative analysis were considered for the present study. Phenotyping of superoxide dismutase was carried out by subjecting the RBC membranes to polyacrylamide gel electrophoresis, using appropriate staining protocols. Results:Statistical analysis of SOD phenotypes revealed a significant increase of SOD AFNx012 allele and Superoxide dismutases (SOD 2-2 phenotype in duodenal ulcer group. Among these individuals, a predominance of Helicobacter pylori infection was observed. The increased preponderance of homozygotes can be explained on the basis of reduced and altered enzyme activity, which may lead to disturbance in homeostasis of antioxidant/oxidant culminating in high lipid peroxidative gastric mucosal tissue damage and ulceration. No variation in the distribution of SOD phenotypes with respect to Helicobacter pylori indicates the role of Mn-SOD rather than Cu-Zn SOD in the Helicobacter pylori infected cases as reported earlier. Conclusions:Superoxide dismutase as a genetic marker / gene modifier, encoding for an antioxidant enzyme in maintaining tissue homeostasis of the gastric mucosa is discussed.

  16. Recognizing asthma mimics and asthma complications.

    Science.gov (United States)

    Amundson, Dennis; Seda, Gilbert; Daheshia, Massoud

    2011-10-01

    Asthma is a chronic inflammatory disorder of the airways characterized by airflow obstruction, bronchial hyperreactivity, and underlying inflammation. Two common reasons asthmatics fail standard therapy are incorrect diagnosis and failure to recognize underlying contributing factors. A correct diagnosis of asthma is of great importance to military practitioners since misdiagnosis or uncontrolled asthma affects an individual's operational readiness or determines whether one can receive a medical waiver to enlist in military service. This article presents four cases of patients with dyspnea that have conditions which mimic asthma or complicate asthma management: vocal cord dysfunction misdiagnosed as asthma, respiratory bronchiolitis interstitial lung disease mistaken as asthma, difficult-to-control asthma because of bronchiectasis and allergic bronchopulmonary aspergillosis, and difficult and fatal asthma. Asthma is contrasted to other respiratory disorders, and an outlined approach to asthma diagnosis and management is presented using the Global Initiative for Asthma guidelines.

  17. Renewable polyethylene mimics derived from castor oil.

    Science.gov (United States)

    Türünç, Oĝuz; Montero de Espinosa, Lucas; Meier, Michael A R

    2011-09-01

    An increasing number of reports on the syntheses of carbohydrate- and plant oil-based polymers has been published in ongoing efforts to produce plastic materials from renewable resources. Although many of these polymers are biodegradable and this is a desirable property for certain applications, in some cases non-degradable polymers are needed for long-term use purposes. Polyolefins are one of the most important classes of materials that have already taken their places in our daily life. On the other hand, their production relies on fossil resources. Therefore, within this contribution, we discuss synthetic routes toward a number of polyethylene mimics derived from fatty acids via thiol-ene and ADMET polymerization reactions in order to establish more sustainable routes toward this important class of polymers. Two different diene monomers were thus prepared from castor oil derived platform chemicals, their polymerization via the two mentioned routes was optimized and compared to each other, and their thermal properties were investigated.

  18. Berberine inhibits PTP1B activity and mimics insulin action.

    Science.gov (United States)

    Chen, Chunhua; Zhang, Yuebo; Huang, Cheng

    2010-07-02

    Type 2 diabetes patients show defects in insulin signal transduction that include lack of insulin receptor, decrease in insulin stimulated receptor tyrosine kinase activity and receptor-mediated phosphorylation of insulin receptor substrates (IRSs). A small molecule that could target insulin signaling would be of significant advantage in the treatment of diabetes. Berberine (BBR) has recently been shown to lower blood glucose levels and to improve insulin resistance in db/db mice partly through the activation of AMP-activated protein kinase (AMPK) signaling and induction of phosphorylation of insulin receptor (IR). However, the underlying mechanism remains largely unknown. Here we report that BBR mimics insulin action by increasing glucose uptake ability by 3T3-L1 adipocytes and L6 myocytes in an insulin-independent manner, inhibiting phosphatase activity of protein tyrosine phosphatase 1B (PTP1B), and increasing phosphorylation of IR, IRS1 and Akt in 3T3-L1 adipocytes. In diabetic mice, BBR lowers hyperglycemia and improves impaired glucose tolerance, but does not increase insulin release and synthesis. The results suggest that BBR represents a different class of anti-hyperglycemic agents.

  19. Decorin mimic inhibits vascular smooth muscle proliferation and migration.

    Directory of Open Access Journals (Sweden)

    Rebecca A Scott

    Full Text Available Over the past 10 years, the number of percutaneous coronary intervention procedures performed in the United States increased by 33%; however, restenosis, which inhibits complete functional recovery of the vessel wall, complicates this procedure. A wide range of anti-restenotic therapeutics have been developed, although many elicit non-specific effects that compromise vessel healing. Drawing inspiration from biologically-relevant molecules, our lab developed a mimic of the natural proteoglycan decorin, termed DS-SILY, which can mask exposed collagen and thereby effectively decrease platelet activation, thus contributing to suppression of vascular intimal hyperplasia. Here, we characterize the effects of DS-SILY on both proliferative and quiescent human SMCs to evaluate the potential impact of DS-SILY-SMC interaction on restenosis, and further characterize in vivo platelet interactions. DS-SILY decreased proliferative SMC proliferation and pro-inflammatory cytokine secretion in vitro in a concentration dependent manner as compared to untreated controls. The addition of DS-SILY to in vitro SMC cultures decreased SMC migration and protein synthesis by 95% and 37%, respectively. Furthermore, DS-SILY decreased platelet activation, as well as reduced neointimal hyperplasia by 60%, in vivo using Ossabaw swine. These results indicate that DS-SILY demonstrates multiple biological activities that may all synergistically contribute to an improved treatment paradigm for balloon angioplasty.

  20. Designing mimics of membrane active proteins.

    Science.gov (United States)

    Sgolastra, Federica; Deronde, Brittany M; Sarapas, Joel M; Som, Abhigyan; Tew, Gregory N

    2013-12-17

    As a semipermeable barrier that controls the flux of biomolecules in and out the cell, the plasma membrane is critical in cell function and survival. Many proteins interact with the plasma membrane and modulate its physiology. Within this large landscape of membrane-active molecules, researchers have focused significant attention on two specific classes of peptides, antimicrobial peptides (AMPs) and cell penetrating peptides (CPPs), because of their unique properties. In this Account, we describe our efforts over the last decade to build and understand synthetic mimics of antimicrobial peptides (SMAMPs). These endeavors represent one specific example of a much larger effort to understand how synthetic molecules interact with and manipulate the plasma membrane. Using both defined molecular weight oligomers and easier to produce, but heterogeneous, polymers, we have generated scaffolds with biological potency exceeding that of the natural analogues. One of these compounds has progressed through a phase II clinical trial for pan-staph infections. Modern biophysical assays have highlighted the interplay between the synthetic scaffold and lipid composition: a negative Gaussian curvature is required both for pore formation and for the initiation of endosome creation. Although work remains to better resolve the complexity of this interplay between lipids, other bilayer components, and the scaffolds, significant new insights have been discovered. These results point to the importance of considering the various aspects of permeation and how these are related to "pore formation". More recently, our efforts have expanded toward protein transduction domains, or mimics of cell penetrating peptides. Using a combination of unique molecular scaffolds and guanidinium-rich side chains, we have produced an array of polymers with robust membrane (and delivery) activity. In this new area, researchers are just beginning to understand the fundamental interactions between these new

  1. Ras Oncogene-Mediated Progressive Silencing of Extracellular Superoxide Dismutase in Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Francesca Cammarota

    2015-01-01

    Full Text Available Extracellular superoxide dismutase (SOD3 is a secreted enzyme that uses superoxide anion as a substrate in a dismutase reaction that results in the formation of hydrogen peroxide. Both of these reactive oxygen species affect growth signaling in cells. Although SOD3 has growth-supporting characteristics, the expression of SOD3 is downregulated in epithelial cancer cells. In the current work, we studied the mechanisms regulating SOD3 expression in vitro using thyroid cell models representing different stages of thyroid cancer. We demonstrate that a low level of RAS activation increases SOD3 mRNA synthesis that then gradually decreases with increasing levels of RAS activation and the decreasing degree of differentiation of the cancer cells. Our data indicate that SOD3 regulation can be divided into two classes. The first class involves RAS–driven reversible regulation of SOD3 expression that can be mediated by the following mechanisms: RAS GTPase regulatory genes that are responsible for SOD3 self-regulation; RAS-stimulated p38 MAPK activation; and RAS-activated increased expression of the mir21 microRNA, which inversely correlates with sod3 mRNA expression. The second class involves permanent silencing of SOD3 mediated by epigenetic DNA methylation in cells that represent more advanced cancers. Therefore, the work suggests that SOD3 belongs to the group of ras oncogene-silenced genes.

  2. Differential effects of superoxide dismutase and superoxide dismutase/catalase mimetics on human breast cancer cells.

    Science.gov (United States)

    Shah, Manisha H; Liu, Guei-Sheung; Thompson, Erik W; Dusting, Gregory J; Peshavariya, Hitesh M

    2015-04-01

    Reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H2O2) have been implicated in development and progression of breast cancer. In the present study, we have evaluated the effects of the superoxide dismutase (SOD) mimetic MnTmPyP and the SOD/catalase mimetic EUK 134 on superoxide and H2O2 formation as well as proliferation, adhesion, and migration of MCF-7 and MDA-MB-231 cells. Superoxide and H2O2 production was examined using dihydroethidium and Amplex red assays, respectively. Cell viability and adhesion were measured using a tetrazolium-based MTT assay. Cell proliferation was determined using trypan blue assay. Cell cycle progression was analyzed using flow cytometry. Clonal expansion of a single cell was performed using a colony formation assay. Cell migration was measured using transwell migration assay. Dual luciferase assay was used to determine NF-κB reporter activity. EUK 134 effectively reduced both superoxide and H2O2, whereas MnTmPyP removed superoxide but enhanced H2O2 formation. EUK 134 effectively attenuated viability, proliferation, clonal expansion, adhesion, and migration of MCF-7 and MDA-MB-231 cells. In contrast, MnTmPyP only reduced clonal expansion of MCF-7 and MDA-MB-231 cells but had no effect on adhesion and cell cycle progression. Tumor necrosis factor-alpha-induced NF-κB activity was reduced by EUK 134, whereas MnTmPyP enhanced this activity. These data indicate that the SOD mimetic MnTmPyP and the SOD/catalase mimetic EUK 134 exert differential effects on breast cancer cell growth. Inhibition of H2O2 signaling using EUK 134-like compound might be a promising approach to breast cancer therapy.

  3. Cu/Zn superoxide dismutases in developing cotton fibers

    Science.gov (United States)

    Hydrogen peroxide (H2O2) and other reactive oxygen species (ROS) are important signaling molecules in diverse physiological processes. Previously, we discovered superoxide dismutase (SOD) activity in extracellular protein preparations from fiber-bearing cotton (Gossypium hirsutum L.) seeds. We sho...

  4. Superoxide dismutase in the marine sponge Cliona celata

    NARCIS (Netherlands)

    Marques, D.; Esteves, A.I.; Almeida, M.; Xavier, J.; Humanes, M.

    2008-01-01

    The aim of this work is to investigate the activity of the antioxidant enzyme superoxide dismutase in the cosmopolitan sponge Cliona celata (Grant, 1826), since this enzyme has been described as a useful biomarker for marine pollution in other marine invertebrates. The quantification of the catalyti

  5. Computing Stability Effects of Mutations in Human Superoxide Dismutase 1

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2014-01-01

    Protein stability is affected in several diseases and is of substantial interest in efforts to correlate genotypes to phenotypes. Superoxide dismutase 1 (SOD1) is a suitable test case for such correlations due to its abundance, stability, available crystal structures and thermochemical data...

  6. Superoxide dismutase in the marine sponge Cliona celata

    NARCIS (Netherlands)

    Marques, D.; Esteves, A.I.; Almeida, M.; Xavier, J.; Humanes, M.

    2008-01-01

    The aim of this work is to investigate the activity of the antioxidant enzyme superoxide dismutase in the cosmopolitan sponge Cliona celata (Grant, 1826), since this enzyme has been described as a useful biomarker for marine pollution in other marine invertebrates. The quantification of the

  7. Effect of Low Level Cadmium Exposure on Superoxide Dismutase ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research January 2016; 15 (1): 115-119. ISSN: 1596-5996 ... Results: The data revealed a significant (p < 0.05) decrease in organ weight of the exposed rats, and with the highest ... system such as superoxide dismutase. Antioxidants ... the guiding principles of laboratory animal care.

  8. Effect of yogic exercise on superoxide dismutase levels in diabetics

    Directory of Open Access Journals (Sweden)

    Mahapure Hemant

    2008-01-01

    Full Text Available Context: Reactive oxygen species are known to aggravate disease progression. To counteract their harmful effects, the body produces various antioxidant enzymes, viz , superoxide dismutase, glutathione reductase etc. Literature reviews revealed that exercises help to enhance antioxidant enzyme systems; hence, yogic exercises may be useful to combat various diseases. Aims: This study aims to record the efficacy of yoga on superoxide dismutase, glycosylated hemoglobin (Hb and fasting blood glucose levels in diabetics. Settings and Design: Forty diabetics aged 40-55 years were assigned to experimental (30 and control (10 groups. The experimental subjects underwent a Yoga program comprising of various Asanas (isometric type exercises and Pranayamas (breathing exercises along with regular anti-diabetic therapy whereas the control group received anti-diabetic therapy only. Methods and Material: Heparinized blood samples were used to determine erythrocyte superoxide dismutase (SOD activity and glycosylated Hb levels and fasting blood specimens collected in fluoride Vacutainers were used for assessing blood glucose. Statistical analysis used: Data were analyzed by using 2 x 2 x 3 Factorial ANOVA followed by Scheffe′s posthoc test. Results: The results revealed that Yogic exercise enhanced the levels of Superoxide dismutase and reduced glycosylated Hb and glucose levels in the experimental group as compared to the control group. Conclusion: The findings conclude that Yogic exercises have enhanced the antioxidant defence mechanism in diabetics by reducing oxidative stress.

  9. Retropharyngeal Calcific Tendonitis Mimics a Retropharyngeal Abscess

    Directory of Open Access Journals (Sweden)

    Natasha Pollak

    2013-01-01

    Full Text Available Retropharyngeal calcific tendonitis (RCT is an uncommon, self-limiting condition that is often omitted in the differential diagnosis of a retropharyngeal fluid collection. This condition mimics a retropharyngeal abscess and should be considered when evaluating a fluid collection in the retropharyngeal space. Although calcific tendonitis at other sites has been well described in the medical literature, it appears that this entity has been underreported in the otolaryngology literature where only a few case reports have been identified. Presumably, the actual incidence is higher than the reported incidence, due to lack of familiarity with this disorder. As an otolaryngologist’s scope of practice includes the managements of retropharyngeal lesions, it is important for the otolaryngologist to recognize the presentation of acute RCT and be familiar with appropriate treatment strategies. Retropharyngeal calcific tendonitis presents with neck pain, limitation of neck range of motion and includes inflammation, calcifications, and a sterile effusion within the longus colli muscle. Treatment is medical with nonsteroidal anti-inflammatory medications. RCT does not require surgical treatment, and an accurate diagnosis can prevent unnecessary attempts at operative drainage. In this study, we discuss two cases of RCT, summarize the salient features in diagnosis, including key radiologic features, discuss treatment options, and review the literature.

  10. Mycosis Fungoides mimic chronic eczema? Observation

    Directory of Open Access Journals (Sweden)

    Jacek Andruszkiewicz

    2013-07-01

    Full Text Available Mycosis fungoides (MF is the most common type of cutaneous T-cell lymphoma [1]. Because of its great variety of clinical features and nonspecific histological findings (especially in early stages has been named the "great imitator "and can induce many wrong diagnosis [2,3]. Mycosis fungoides (MF, is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known [4,5]. Therefore very often Mycosis fungoides is misdiagnosed as chronic eczema [6]. MF can also mimic: vitiligo [6], alopecia-Areata [7], ecchymosis [8].

  11. Superoxide dismutase activity of the naturally occurring human serum albumin-copper complex without hydroxyl radical formation.

    Science.gov (United States)

    Kato, Ryunosuke; Akiyama, Matofusa; Kawakami, Hiroyoshi; Komatsu, Teruyuki

    2014-01-01

    The superoxide radical anion (O2(.-)) is biologically toxic and contributes to the pathogenesis of various diseases. Here we describe the superoxide dismutase (SOD) activity of human serum albumin (HSA) complexed with a single Cu(II) ion at the N-terminal end (HSA-Cu complex). The structure of this naturally occurring copper-coordinated blood serum protein has been characterized by several physicochemical measurements. The O2(.-) dismutation ability of the HSA-Cu (1:1) complex is almost the same as that of the well-known SOD mimics, such as Mn(III) -tetrakis(N-methylpyridinium)porphyrin. Interestingly, the HSA-Cu complex does not induce a subsequent Fenton reaction to produce the hydroxyl radical (OH(.)), which is one of the most harmful reactive oxygen species.

  12. New strigolactone mimics: structure-activity relationship and mode of action as germinating stimulants for parasitic weeds.

    Science.gov (United States)

    Zwanenburg, Binne; Nayak, Sandip K; Charnikhova, Tatsiana V; Bouwmeester, Harro J

    2013-09-15

    Strigolactones (SLs) are new plant hormones with varies important bio-functions. This Letter deals with germination of seeds of parasitic weeds. Natural SLs have a too complex structure for synthesis. Therefore, there is an active search for SL analogues and mimics with a simpler structure with retention of activity. SL analogues all contain the D-ring connected with an enone moiety through an enol ether unit. A new mechanism for the hydrolysis SL analogues involving bidentate bound water and an α,β-hydrolase with a Ser-His-Asp catalytic triad has been proposed. Newly discovered SL mimics only have the D-ring with an appropriate leaving group at C-5. A mode of action for SL mimics was proposed for which now supporting evidence is provided. As predicted an extra methyl group at C-4 of the D-ring blocks the germination of seeds of parasitic weeds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. ACTIVITY OF SUPEROXIDE DISMUTASE ENZYME IN YEAST SACCHAROMYCES CEREVISIAE

    OpenAIRE

    2014-01-01

    Reactive oxygen species (ROS) with reactive nitrogen species (RNS) are known to play dual role in biological systems, they can be harmful or beneficial to living systems. ROS can be important mediators of damage to cell structures, including proteins, lipids and nucleic acids termed as oxidative stress. The antioxidant enzymes protect the organism against the oxidative damage caused by active oxygen forms. The role of superoxide dismutase (SOD) is to accelerate the dismutation of the toxic su...

  14. Levels of Malondialdehyde and Superoxide Dismutase in Subclinical Hyperthyroidism

    OpenAIRE

    2005-01-01

    We aimed to determine whether patients with subclinical hyperthyroidism (SH) are subject to oxidative stress. Twenty-two women and 8 men having endogenous subclinical hyperthyroidism for a duration of at least 6 months, and 21 women and 9 men healthy controls were included in this study. We measured the level of plasma malondialdehyde, as one of the lipid peroxidation markers, and the activity of erythrocyte superoxide dismutase, which is an antioxidant enzyme. The activity of erythrocyte sup...

  15. Recognition of extended linear and cyclised polyketide mimics by a type II acyl carrier protein.

    Science.gov (United States)

    Dong, Xu; Bailey, Christopher D; Williams, Christopher; Crosby, John; Simpson, Thomas J; Willis, Christine L; Crump, Matthew P

    2016-03-01

    Polyketides are secondary metabolites which display both valuable pharmaceutical and agrochemical properties. Biosynthesis is performed by polyketide synthases (PKSs), and the acyl carrier protein (ACP), a small acidic protein, that transports the growing polyketide chain and is essential for activity. Here we report the synthesis of two aromatic probes and a linear octaketide mimic that have been tethered to actinorhodin ACP. These experiments were aimed at probing the ACP's capacity to sequester a non-polar versus a phenolic aromatic ring (that more closely mimics a polyketide intermediate) as well as investigations with extended polyketide chain surrogates. The binding of these mimics has been assessed using high-resolution solution NMR studies and high-resolution structure determination. These results reveal that surprisingly a PKS ACP is able to bind and sequester a bulky non-polar substrate containing an aromatic ring in a fatty acid type binding mode, but the introduction of even a small degree of polarity favours a markedly different association at a surface site that is distinct from that employed by fatty acid ACPs.

  16. Impact of Thyroid Dysfunction on Antioxidant Capacity, Superoxide Dismutase

    Directory of Open Access Journals (Sweden)

    Mehdi Hedayati

    2014-01-01

    Full Text Available Background: In hypothyroidism and hyperthyroidism, disturbance of oxidant/antioxidant balance leads to reactive oxygen species (ROS generation. The aim of this study is assaying total antioxidant capacity and superoxide dismutase and catalase activities in patients with hypo-and hyperthyroidism in order to control the progression of its pathology and health care. Materials and Methods: This case-control study was performed on 85 patients with hypothyroidism, 66 patients with hyperthyroidism and 74 normal individuals as control that referred to the clinic of the Research Institute for Endocrine Sciences of Shahid-Beheshti University in year 2010. Serum enzymatic activity of catalase, superoxide dismutase and total antioxidant capacity was measured in the fasting state. Data was described as mean±SD and data means of the two groups was compared by independent t-test. Data was analyzed by SPSS-18 application. Results: The total antioxidant capacity in individuals with hyperthyroidism decreased compared to healthy controls, but individuals with hypothyroidism compared to the healthy control group showed no significant difference. Catalase and superoxide dismutase activity in hypo-and hyperthyroidism were significantly increased compared with healthy controls (p=0.005. Conclusion: Decreasing of antioxidant capacity in hyperthyroid patients is probably because of increased production of free radicals. There was not observed significant difference in total antioxidant capacity in hypothyroid patients. Also in hypo-and hyperthyroidism patients, increasing of enzymes activity is probably due to increasing of the production of ROS.

  17. Fe-TAML encapsulated inside mesoporous silica nanoparticles as peroxidase mimic: femtomolar protein detection.

    Science.gov (United States)

    Kumari, Sushma; Dhar, Basab B; Panda, Chakadola; Meena, Abhishek; Sen Gupta, Sayam

    2014-08-27

    Peroxidase, such as horseradish peroxidase (HRP), conjugated to antibodies are routinely used for the detection of proteins via an ELISA type assay in which a critical step is the catalytic signal amplification by the enzyme to generate a detectable signal. Synthesis of functional mimics of peroxidase enzyme that display catalytic activity which far exceeds the native enzyme is extremely important for the precise and accurate determination of very low quantities of proteins (fM and lower) that is necessary for early clinical diagnosis. Despite great advancements, analyzing proteins of very low abundance colorimetrically, a method that is most sought after since it requires no equipment for the analysis, still faces great challenges. Most reported HRP mimics that show catalytic activity greater than native enzyme (∼10-fold) are based on metal/metal-oxide nanoparticles such as Fe3O4. In this paper, we describe a second generation hybrid material developed by us in which approximately 25,000 alkyne tagged biuret modified Fe-tetraamido macrocyclic ligand (Fe-TAML), a very powerful small molecule synthetic HRP mimic, was covalently attached inside a 40 nm mesoporous silica nanoparticle (MSN). Biuret-modified Fe-TAMLs represent one of the best small molecule functional mimics of the enzyme HRP with reaction rates in water close to the native enzyme and operational stability (pH, ionic strength) far exceeding the natural enzyme. The catalytic activity of this hybrid material is around 1000-fold higher than that of natural HRP and 100-fold higher than that of most metal/metal oxide nanoparticle based HRP mimics reported to date. We also show that using antibody conjugates of this hybrid material it is possible to detect and, most importantly, quantify femtomolar quantities of proteins colorimetrically in an ELISA type assay. This represents at least 10-fold higher sensitivity than other colorimetric protein assays that have been reported using metal/metal oxide

  18. Glutathione transferase mimics : Micellar catalysis of an enzymic reaction

    NARCIS (Netherlands)

    Lindkvist, Björn; Weinander, Rolf; Engman, Lars; Koetse, Marc; Engberts, Jan B.F.N.; Morgenstern, Ralf

    1997-01-01

    Substances that mimic the enzyme action of glutathione transferases (which serve in detoxification) are described. These micellar catalysts enhance the reaction rate between thiols and activated halogenated nitroarenes as well as alpha,beta-unsaturated carbonyls. The nucleophilic aromatic substituti

  19. Superoxide dismutase levels and peak expiratory flow in asthmatic children

    Directory of Open Access Journals (Sweden)

    Arie Kurniasih

    2015-09-01

    Full Text Available Background Asthma is a chronic inflammatory process which involve variety of cells such as inflammatory mediators, reactive oxygen species (ROS, and cytokines. The inflammatory process would be exacerbated in the presence of oxidative stress. Superoxide dismutase (SOD is the first important enzyme to protect the respiratory tract against oxidative stress. The decreased of SOD has a correlation with increased of airway obstruction and bronchospasm. Objective To assess for a correlation between superoxide dismutase (SOD levels and peak expiratory flow, as well as to determine the impact of SOD levels for predicting asthma attacks. Methods We conducted a prospective cohort study at Dr. Sardjito Hospital, Yogyakarta, between February and April 2011 involving asthmatic children aged 5-18 years. Subjects’ serum SOD levels and peak expiratory flow were measured at the same time point. We then performed a prospective study following up on the same subjects to find out if they had a recurrent asthma attack within one month of the tests. We also reassessed their peak expiratory flow one month after blood specimens were obtained. Results Thirty-nine patients were enrolled in this study. There was no significant correlation between SOD level and peak expiratory flow [r=0.289; 95%CI -0.025 to 0.47; P=0.074]. However, older age was significantly associated with higher peak expiratory flow (=0.5; 95%CI 3.10 to 11.57; P=0.01. Lower levels of SOD increased the risk of asthma attacks in a month following the initial measurements (RR=5.5; 95%CI 1.6 to 18.9; P=0.009. Conclusion Superoxide dismutase (SOD level is not significantly associated with peak expiratory flow. However, we find a relationship between older age and higher peak expiratory flow and a relationship between lower SOD levels and risk of asthma attacks within one month following the tests.

  20. Superoxide dismutase levels and peak expiratory flow in asthmatic children

    Directory of Open Access Journals (Sweden)

    Arie Kurniasih

    2016-11-01

    Full Text Available involvevariety of cells such as inflammatory mediators, reactive oxygenspecies (ROS, and cytokines. The inflammatory process would beexacerbated in the presence of oxidative stress. Superoxide dismutase(SOD is the first important enzyme to protect the respiratory tractagainst oxidative stress. The decreased of SOD has a correlation withincreased of airway obstruction and bronchospasm.Objective To assess for a correlation between superoxide dismutase(SOD levels and peak expiratory flow, as well as to determinethe impact of SOD levels for predicting asthma attacks.Methods We conducted a prospective cohort study at Dr. SardjitoHospital, Yogyakarta, between February and April 2011 involvingasthmatic children aged 5-18 years. Subjects’ serum SOD levelsand peak expiratory flow were measured at the same time point.We then performed a prospective study following up on the samesubjects to find out if they had a recurrent asthma attack withinone month of the tests. We also reassessed their peak expiratoryflow one month after blood specimens were obtained.Results Thirty-nine patients were enrolled in this study. Therewas no significant correlation between SOD level and peakexpiratory flow [r=0.289; 95%CI -0.025 to 0.47; P=0.074].However, older age was significantly associated with higher peakexpiratory flow (=0.5; 95%CI 3.10 to 11.57; P=0.01. Lowerlevels of SOD increased the risk of asthma attacks in a monthfollowing the initial measurements (RR=5.5; 95%CI 1.6 to 18.9;P=0.009.Conclusion Superoxide dismutase (SOD level is not significantlyassociated with peak expiratory flow. However, we find arelationship between older age and higher peak expiratory flowand a relationship between lower SOD levels and risk of asthmaattacks within one month following the tests. [

  1. Differential pH sensitivity of tissue superoxide dismutases

    OpenAIRE

    Patel, Samir P.; Katyare, Surendra S.

    2006-01-01

    Superoxide dismutase (SOD) activities in the human and rat RBCs and rat liver, kidney, brain and heart mitochondria as well as cytosolic fractions were determined by the pyrogallol assay procedure with slight modifications. Measurements were carried out in 0.1 M potassium phosphate buffer pH 8.0 and 9.2 to assess the pH stability of the SODs from various systems. Under these conditions the SODs from different systems including RBCs exhibited differential pH stability i.e. they displayed diffe...

  2. Rational Design of Superoxide Dismutase (SOD) Mimics: The Evaluation of the Therapeutic Potential of New Cationic Mn Porphyrins with Linear and Cyclic Substituents

    Science.gov (United States)

    2015-01-01

    Our goal herein has been to gain further insight into the parameters which control porphyrin therapeutic potential. Mn porphyrins (MnTnOct-2-PyP5+, MnTnHexOE-2-PyP5+, MnTE-2-PyPhP5+, and MnTPhE-2-PyP5+) that bear the same positive charge and same number of carbon atoms at meso positions of porphyrin core were explored. The carbon atoms of their meso substituents are organized to form either linear or cyclic structures of vastly different redox properties, bulkiness, and lipophilicities. These Mn porphyrins were compared to frequently studied compounds, MnTE-2-PyP5+, MnTE-3-PyP5+, and MnTBAP3–. All Mn(III) porphyrins (MnPs) have metal-centered reduction potential, E1/2 for MnIIIP/MnIIP redox couple, ranging from −194 to +340 mV versus NHE, log kcat(O2•–) from 3.16 to 7.92, and log kred(ONOO–) from 5.02 to 7.53. The lipophilicity, expressed as partition between n-octanol and water, log POW, was in the range −1.67 to −7.67. The therapeutic potential of MnPs was assessed via: (i) in vitro ability to prevent spontaneous lipid peroxidation in rat brain homogenate as assessed by malondialdehyde levels; (ii) in vivo O2•– specific assay to measure the efficacy in protecting the aerobic growth of SOD-deficient Saccharomyces cerevisiae; and (iii) aqueous solution chemistry to measure the reactivity toward major in vivo endogenous antioxidant, ascorbate. Under the conditions of lipid peroxidation assay, the transport across the cellular membranes, and in turn shape and size of molecule, played no significant role. Those MnPs of E1/2 ∼ +300 mV were the most efficacious, significantly inhibiting lipid peroxidation in 0.5–10 μM range. At up to 200 μM, MnTBAP3– (E1/2 = −194 mV vs NHE) failed to inhibit lipid peroxidation, while MnTE-2-PyPhP5+ with 129 mV more positive E1/2 (−65 mV vs NHE) was fully efficacious at 50 μM. The E1/2 of MnIIIP/MnIIP redox couple is proportional to the log kcat(O2•–), i.e., the SOD-like activity of MnPs. It is further proportional to kred(ONOO–) and the ability of MnPs to prevent lipid peroxidation. In turn, the inhibition of lipid peroxidation by MnPs is also proportional to their SOD-like activity. In an in vivo S. cerevisiae assay, however, while E1/2 predominates, lipophilicity significantly affects the efficacy of MnPs. MnPs of similar log POW and E1/2, that have linear alkyl or alkoxyalkyl pyridyl substituents, distribute more easily within a cell and in turn provide higher protection to S. cerevisiae in comparison to MnP with bulky cyclic substituents. The bell-shape curve, with MnTE-2-PyP5+ exhibiting the highest ability to catalyze ascorbate oxidation, has been established and discussed. Our data support the notion that the SOD-like activity of MnPs parallels their therapeutic potential, though species other than O2•–, such as peroxynitrite, H2O2, lipid reactive species, and cellular reductants, may be involved in their mode(s) of action(s). PMID:25333724

  3. Characterization and mapping of a novel light-dependent lesion mimic mutant lmm6 in rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    XIAO Gui-qing; ZHANG Hai-wen; LU Xiang-yang; HUANG Rong-feng

    2015-01-01

    A novel rice lesion mimic mutant (LMM) was isolated from an ethane methyl sulfonate (EMS)-induced 02428 mutant bank. The mutant, tentatively designated as lmm6, develops necrotic lesions in the whole growth period along with changes in several important agronomic traits. We found that the initiation of the lesions was induced by light and cel death occurred in lmm6 accompanied with accumulation of reactive oxygen species (ROS). The lower chlorophyl content, soluble protein content and superoxide dismutase (SOD) activity, the higher malondialdehyde (MDA) content were detected in lmm6 than in the wild type (WT). Moreover, the observation by transmission electronic microscope (TEM) demonstrated that some organel es were damaged and the stroma lamel a of chloroplast was irregular and loose in mesophyl cel of lmm6. In addition, lmm6 was more resistant than WT to rice blast fungus Magnaporthe grisea infection, which was consistent with increased expression of four genes involved in the defense-related reaction. Genetic analysis showed that mutant trait of lmm6 is inherited as a monogenic recessive nuclear gene located on the long arm of chromosome 6. Using simple sequence repeat (SSR) markers, the target gene was ifnal y delimited to an interval of 80.8 kb between markers MM2359 and MM2370, containing 7 annotated genes. Taken together, our results provide the information to identify a new gene involved in rice lesion mimic, which wil be helpful in clarifying the mechanism of cel death and disease resistance in rice.

  4. A Batesian mimic and its model share color production mechanisms

    Institute of Scientific and Technical Information of China (English)

    David W.KIKUCHI; David W.PFENNIG

    2012-01-01

    Batesian mimics are harmless prey species that resemble dangerous ones (models),and thus receive protection from predators.How such adaptive resemblances evolve is a classical problem in evolutionary biology.Mimicry is typically thought to be difficult to evolve,especially if the model and mimic produce the convergent phenotype through different proximate mechanisms.However,mimicry may evolve more readily if mimic and model share similar pathways for producing the convergent phenotype.In such cases,these pathways can be co-opted in ancestral mimic populations to produce high-fidelity mimicry without the need for major evolutionary innovations.Here,we show that a Batesian mimic,the scarlet kingsnake Lampropettis elapsoides,produces its coloration using the same physiological mechanisms as does its model,the eastern coral snake Micrurus fulvius.Therefore,precise color mimicry may have been able to evolve easily in this system.Generally,we know relatively little about the proximate mechanisms underlying mimicry.

  5. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  6. SuperMimic – Fitting peptide mimetics into protein structures

    Directory of Open Access Journals (Sweden)

    Schmidt Ulrike

    2006-01-01

    Full Text Available Abstract Background Various experimental techniques yield peptides that are biologically active but have unfavourable pharmacological properties. The design of structurally similar organic compounds, i.e. peptide mimetics, is a challenging field in medicinal chemistry. Results SuperMimic identifies compounds that mimic parts of a protein, or positions in proteins that are suitable for inserting mimetics. The application provides libraries that contain peptidomimetic building blocks on the one hand and protein structures on the other. The search for promising peptidomimetic linkers for a given peptide is based on the superposition of the peptide with several conformers of the mimetic. New synthetic elements or proteins can be imported and used for searching. Conclusion We present a graphical user interface for finding peptide mimetics that can be inserted into a protein or for fitting small molecules into a protein. Using SuperMimic, promising locations in proteins for the insertion of mimetics can be found quickly and conveniently.

  7. SuperMimic – Fitting peptide mimetics into protein structures

    Science.gov (United States)

    Goede, Andrean; Michalsky, Elke; Schmidt, Ulrike; Preissner, Robert

    2006-01-01

    Background Various experimental techniques yield peptides that are biologically active but have unfavourable pharmacological properties. The design of structurally similar organic compounds, i.e. peptide mimetics, is a challenging field in medicinal chemistry. Results SuperMimic identifies compounds that mimic parts of a protein, or positions in proteins that are suitable for inserting mimetics. The application provides libraries that contain peptidomimetic building blocks on the one hand and protein structures on the other. The search for promising peptidomimetic linkers for a given peptide is based on the superposition of the peptide with several conformers of the mimetic. New synthetic elements or proteins can be imported and used for searching. Conclusion We present a graphical user interface for finding peptide mimetics that can be inserted into a protein or for fitting small molecules into a protein. Using SuperMimic, promising locations in proteins for the insertion of mimetics can be found quickly and conveniently. PMID:16403211

  8. Levels of erythrocyte superoxide dismutase activity in Japanese people

    Directory of Open Access Journals (Sweden)

    Ueda,Kazuko

    1978-12-01

    Full Text Available Levels of erythrocyte superoxide dismutase (SOD activitiy in a sample of Japanese people were determined. Blood samples were taken from new-born infants, preschool children, young and old people who had no apparent diseases and also from three anemic patients. Erythrocyte SOD activities in different age groups had a nearly normal distribution. Females had slightly lower activities than males, although the difference was statistically insignificant. The distributions of SOD activities were 12.6 +/- 2.7 (m +/- SD unit/mg Hb in young people and 11.4 +/- 3.0 in old people, indicating that erythrocyte SOD activity falls with aging. Because of low concentration of hemoglobin, SOD activities of old people expressed as unit/ml blood were much lower than in young people. Three anemic patients had slightly lower SOD activity.

  9. Superoxide Dismutase and Catalase Genotypes in Pediatric Migraine Patients.

    Science.gov (United States)

    Saygi, Semra; Erol, İlknur; Alehan, Füsun; Yalçın, Yaprak Yılmaz; Kubat, Gözde; Ataç, Fatma Belgin

    2015-10-01

    This study compared superoxide dismutase (SOD) and catalase (CAT) alleles in 97 consecutive children and adolescents with migraine to 96 healthy children and adolescents. Isolated genomic DNA was used as a template for SOD1 (35 A/C), SOD2 16 C/T, and CAT2 [(-262 C/T) and (-21 A/T)] allele genotyping. The SOD2 16 C/T genotype and C allele frequency differed significantly between controls and migraine (P = .047; P = .038). CAT -21 AA genotype and A allele frequency were significantly higher in both migraine with aura patients (P = .013; P = .004) and migraine without aura patients (P = .003; P = .001) compared to controls. To our knowledge, this is the first demonstration of differences in SOD and CAT genotypes between pediatric migraine patients and age-matched controls. Further studies on the functional implications of these genetic variants on neural antioxidant capacity and the use of antioxidant modulators for migraine treatment are warranted.

  10. ACTIVITY OF SUPEROXIDE DISMUTASE ENZYME IN YEAST SACCHAROMYCES CEREVISIAE

    Directory of Open Access Journals (Sweden)

    Blažena Lavová

    2014-02-01

    Full Text Available Reactive oxygen species (ROS with reactive nitrogen species (RNS are known to play dual role in biological systems, they can be harmful or beneficial to living systems. ROS can be important mediators of damage to cell structures, including proteins, lipids and nucleic acids termed as oxidative stress. The antioxidant enzymes protect the organism against the oxidative damage caused by active oxygen forms. The role of superoxide dismutase (SOD is to accelerate the dismutation of the toxic superoxide radical, produced during oxidative energy processes, to hydrogen peroxide and molecular oxygen. In this study, SOD activity of three yeast strains Saccharomyces cerevisiae was determined. It was found that SOD activity was the highest (23.7 U.mg-1 protein in strain 612 after 28 hours of cultivation. The lowest SOD activity from all tested strains was found after 56 hours of cultivation of strain Gyöng (0.7 U.mg-1 protein.

  11. Macrocyclic beta-sheet peptides that mimic protein quaternary structure through intermolecular beta-sheet interactions.

    Science.gov (United States)

    Khakshoor, Omid; Demeler, Borries; Nowick, James S

    2007-05-02

    This paper reports the design, synthesis, and characterization of a family of cyclic peptides that mimic protein quaternary structure through beta-sheet interactions. These peptides are 54-membered-ring macrocycles comprising an extended heptapeptide beta-strand, two Hao beta-strand mimics [JACS 2000, 122, 7654] joined by one additional alpha-amino acid, and two delta-linked ornithine beta-turn mimics [JACS 2003, 125, 876]. Peptide 3a, as the representative of these cyclic peptides, contains a heptapeptide sequence (TSFTYTS) adapted from the dimerization interface of protein NuG2 [PDB ID: 1mio]. 1H NMR studies of aqueous solutions of peptide 3a show a partially folded monomer in slow exchange with a strongly folded oligomer. NOE studies clearly show that the peptide self-associates through edge-to-edge beta-sheet dimerization. Pulsed-field gradient (PFG) NMR diffusion coefficient measurements and analytical ultracentrifugation (AUC) studies establish that the oligomer is a tetramer. Collectively, these experiments suggest a model in which cyclic peptide 3a oligomerizes to form a dimer of beta-sheet dimers. In this tetrameric beta-sheet sandwich, the macrocyclic peptide 3a is folded to form a beta-sheet, the beta-sheet is dimerized through edge-to-edge interactions, and this dimer is further dimerized through hydrophobic face-to-face interactions involving the Phe and Tyr groups. Further studies of peptides 3b-3n, which are homologues of peptide 3a with 1-6 variations in the heptapeptide sequence, elucidate the importance of the heptapeptide sequence in the folding and oligomerization of this family of cyclic peptides. Studies of peptides 3b-3g show that aromatic residues across from Hao improve folding of the peptide, while studies of peptides 3h-3n indicate that hydrophobic residues at positions R3 and R5 of the heptapeptide sequence are important in oligomerization.

  12. A superoxide dismutase of metacestodes of Taenia taeniaeformis.

    Science.gov (United States)

    Leid, R W; Suquet, C M

    1986-03-01

    Superoxide dismutase was purified from Taenia taeniaeformis metacestodes by sequential ion exchange chromatography on quaternary-amino-ethyl-cellulose, gel filtration chromatography on ACA 44 and ion exchange chromatography on DEAE-cellulose, followed by chromatofocusing on polybuffer exchanger 94. This isolation procedure resulted in the detection of a single protein-staining band on alkaline gels, coincident with enzyme activity. We have, however, detected what appear to be two peaks of enzyme activity within this single protein-staining band. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis using gradient slab gels and analysis under reducing conditions, resulted in the detection of only one protein at an apparent Mr of 16,600, while analysis under non-reducing conditions, gave a single protein of an apparent Mr of 64,000. The isoelectric point of the purified protein is 6.6. Boiling for 3 min completely destroyed the enzyme, whereas incubation for 2 h at 37 degrees C resulted in the loss of 56% of the enzymic activity. Incubation with 10 mM KCN resulted in 83% inhibition of the enzyme. We have detected up to 168 U ml-1 of enzyme activity in the cyst fluid surrounding the parasite in situ. This is the first instance in which any parasite superoxide dismutase has been purified to apparent homogeneity. Parasite-mediated enzymic destruction of superoxide anion can not only protect against oxygen toxicity as a result of normal parasite respiratory processes but also may serve as yet another mechanism used by tissue-dwelling parasites to evade host immunologic attack.

  13. Copper Complexes of Nicotinic-Aromatic Carboxylic Acids as Superoxide Dismutase Mimetics

    Directory of Open Access Journals (Sweden)

    Virapong Prachayasittikul

    2008-12-01

    Full Text Available Nicotinic acid (also known as vitamin B3 is a dietary element essential for physiological and antihyperlipidemic functions. This study reports the synthesis of novel mixed ligand complexes of copper with nicotinic and other select carboxylic acids (phthalic, salicylic and anthranilic acids. The tested copper complexes exhibited superoxide dismutase (SOD mimetic activity and antimicrobial activity against Bacillus subtilis ATCC 6633, with a minimum inhibition concentration of 256 μg/mL. Copper complex of nicotinic-phthalic acids (CuNA/Ph was the most potent with a SOD mimetic activity of IC50 34.42 μM. The SOD activities were observed to correlate well with the theoretical parameters as calculated using density functional theory (DFT at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complex CuNA/Ph was positively correlated with the electron affinity (EA value. The two quantum chemical parameters, highest occupied molecular orbital (HOMO and lowest unoccupied molecular orbital (LUMO, were shown to be appropriate for understanding the mechanism of the metal complexes as their calculated energies show good correlation with the SOD activity. Moreover, copper complex with the highest SOD activity were shown to possess the lowest HOMO energy. These findings demonstrate a great potential for the development of value-added metallovitamin-based therapeutics.

  14. Isolation and characterization of Cu,Zn superoxide dismutase of the shark Prionace glauca.

    Science.gov (United States)

    Galtieri, A; Natoli, G; Lania, A; Calabrese, L

    1986-01-01

    A Cu,Zn superoxide dismutase was purified for the first time from an elasmobranch species (Prionace glauca) and showed the following differences with respect to other animal superoxide dismutases. The enzyme displays a low isoelectric point. The enzyme activity is unusually independent of ionic strength. The isolated enzyme has 30% of its copper in the reduced state.

  15. Calorimetric Study of Thermal Denaturation of Superoxide Dismutase

    Institute of Scientific and Technical Information of China (English)

    王邦宁; 谈夫

    1994-01-01

    The thermal denaturation of superoxide dismutase (SOD) from bovine erythrocytes was studied at various pH values of different buffers and at various concentrations of solutions of two neutral salts by differential scanning calorimetry. The experiments performed indicate that the PIPES is a buffer non-coordinating with the SOD, and that the binding of the anions studied influences more or less the thermal denaturation of SOD, but the effect on the oxidation form of SOD is more apparent. A new conformer of SOD with lower thermostability was discovered by the experiments performed in different buffers at certain pH values higher than the isoelectric point of SOD, or at higher concentrations of neutral salt solutions. The new conformer may be converted irreversibly into the usual conformer with high thermostability during heating. Based on the thermodynamic parameters obtained in distilled water and by thermodynamic analysis using the Ooi’s model, it is revealed that the large enthalpy △Hdc contributed by

  16. A Second Superoxide Dismutase Gene in the Medfly, Ceratitis Capitata

    Science.gov (United States)

    Banks, G. K.; Robinson, A. S.; Kwiatowski, J.; Ayala, F. J.; Scott, M. J.; Kriticou, D.

    1995-01-01

    We report the first case of two Cu/Zn Sod genes (ccSod1 and ccSod2) that have been cloned and sequenced from an insect, the medfly, Ceratitis capitata. Biochemical evidence suggested the presence of two Sod genes in the medfly. The two genes are isolated using different molecular strategies: ccSod1 via cross-hybridization to a genomic library using a heterologous probe and ccSod2 from cDNA using a homologous probe generated by PCR. Sequence analysis shows that ccSod1 and ccSod2 are different genes. The inferred amino sequences show that all essential residues of the active site are strictly conserved, which suggests both genes encode functional Cu/Zn superoxide dismutase (SOD). Phylogenetic analysis by the maximum parsimony method with bootstrap resampling of previously known Cu/Zn SOD reveals two monophyletic groups, vertebrates and insects. The position of ccSOD2 in this phylogeny is undefined with respect to dipteran ccSOD1, vertebrate, plant, fungal, and extracellular Cu/Zn SOD, which suggests that the duplication detected in Ceratitis is ancient, perhaps as old as the origins of the arthropod phylum in the Cambrian more than 500 million years ago. In situ hybridization to polytene chromosomes places the genes on different chromosomes, which is consistent with an ancient gene duplication. PMID:7498747

  17. Superoxide Dismutase 1 Nanozyme for Treatment of Eye Inflammation

    Directory of Open Access Journals (Sweden)

    Olga A. Kost

    2016-01-01

    Full Text Available Use of antioxidants to mitigate oxidative stress during ocular inflammatory diseases has shown therapeutic potential. This work examines a nanoscale therapeutic modality for the eye on the base of antioxidant enzyme, superoxide dismutase 1 (SOD1, termed “nanozyme.” The nanozyme is produced by electrostatic coupling of the SOD1 with a cationic block copolymer, poly(L-lysine-poly(ethyleneglycol, followed by covalent cross-linking of the complexes with 3,3′-dithiobis(sulfosuccinimidylpropionate sodium salt. The ability of SOD1 nanozyme as well as the native SOD1 to reduce inflammatory processes in the eye was examined in vivo in rabbits with immunogenic uveitis. Results suggested that topical instillations of both enzyme forms demonstrated anti-inflammatory activity; however, the nanozyme was much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as the intensities of corneal and iris edema, hyperemia of conjunctiva, lens opacity, fibrin clots, and the protein content in aqueous humor. Clinical findings were confirmed by histological data. Thus, SOD1-containing nanozyme is potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.

  18. Superoxide DismutasE in Spring Barley Caryopses

    Directory of Open Access Journals (Sweden)

    Natálie Březinová Belcredi

    2016-01-01

    Full Text Available Superoxide dismutase (SOD activity was determined in caryopses of spring barley grown in field trials in 2004–2006. A total set under study included five malting varieties with hulled grain, three waxy hull-less and hulled varieties (of US origin, seven lines formed by crossing of the above given varieties and four hull-less lines of Czech origin. SOD activity was determined by a modified method using a Ransod diagnostic kit (RANDOX. The method employs xanthine and xanthine oxidase to generate superoxide radicals which react with 2-(4-iodophenyl-3-(4-nitrophenol-5-phenyltetrazolium chloride (INT to form a red formazan dye. Statistically significantly higher activity was measured in the variety Nordus (131 U.g−1 d.m. and line ME1 (128 U.g−1 d.m. compared to the other varieties/lines (66–111 U.g−1 d.m.. The line ME1 had significantly higher SOD activity in grain versus its parental varieties Kompakt (83 U.g−1 d.m. and Krona (78 U.g−1 d.m.. The results of this study proved the availability of varieties/lines with a higher SOD content, the antioxidant effect of SOD can improve quality of beer and food made from barley.

  19. Enzyme superoxide dismutase in grain of barley and malt

    Directory of Open Access Journals (Sweden)

    Natálie Belcrediová

    2006-01-01

    Full Text Available The aim of the work was modification of superoxide dismutase enzyme (SOD, EC 1.15.1.1 activity analysis in barley grain and identical malts with using of the Ransod set. This set from company Randox were used for enzyme determination in blood samples. This method employs xanthine and xanthine oxidase to generate superoxide radicals, which react with tetrazolium chloride to form a red formazan dye. SOD is classified as natural antioxidants and enzyme plays a significant role at detoxication of products of molecular oxygen degradation. The largest rate of SOD occurs in embryo of barley grain. Its presence in barley grain and malt thus inhibits rancidity of grain during storage and undesirable beer flavour. The line Wabet x Washonubet (in grain-104,93 and malt 152,42 U/g dry matter and the variety Annabell (104,65 a 147,21 U/g dry matter had the highest activity of SOD in grain and malt of barley while the lowest activity was measured in the line KM 1910 (73,15 a 88,16 U/g dry matter and variety Tolar (74,34 a 96,44 U/g dry matter.

  20. Expression of Extracellular Superoxide Dismutase Protein in Diabetes

    Directory of Open Access Journals (Sweden)

    Chul Han Kim

    2013-09-01

    Full Text Available Background Diabetes is characterized by chronic hyperglycemia, which can increase reactiveoxygen species (ROS production by the mitochondrial electron transport chain. The formationof ROS induces oxidative stress and activates oxidative damage-inducing genes in cells. Noresearch has been published on oxidative damage-related extracellular superoxide dismutase(EC-SOD protein levels in human diabetic skin. We investigated the expression of EC-SOD indiabetic skin compared with normal skin tissue in vivo.Methods The expression of EC-SOD protein was evaluated by western blotting in 6 diabeticskin tissue samples and 6 normal skin samples. Immunohistochemical staining was also carriedout to confirm the EC-SOD expression level in the 6 diabetic skin tissue samples.Results The western blotting showed significantly lower EC-SOD protein expression in thediabetic skin tissue than in the normal tissue. Immunohistochemical examination of EC-SODprotein expression supported the western blotting analysis.Conclusions Diabetic skin tissues express a relatively small amount of EC-SOD protein andmay not be protected against oxidative stress. We believe that EC-SOD is related to the alteredmetabolic state in diabetic skin, which elevates ROS production.

  1. Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease.

    Science.gov (United States)

    Tórsdóttir, G; Kristinsson, J; Sveinbjörnsdóttir, S; Snaedal, J; Jóhannesson, T

    1999-11-01

    In a previous study we found copper dyshomeostasis in patients with Alzheimer's disease. In this study, levels of copper in plasma, of ceruloplasmin in serum and ceruloplasmin oxidative activity as well as superoxide dismutase (SOD) activity in erythrocytes were determined in 40 patients with Parkinson's disease and their healthy age- and gender-matched controls. Copper concentrations did not differ significantly in the two groups, whereas both ceruloplasmin concentrations and ceruloplasmin oxidative activity were significantly lower in the patients, also relative to ceruloplasmin mass. SOD activity was not significantly different in the two groups but decreased significantly with the duration of disease. The same was found for ceruloplasmin oxidative activity. Ceruloplasmin oxidative activity and SOD activity did not decrease with age. Levels of serum iron, serum ferritin and total iron binding capacity were determined in about 30 of the patients and an equal number of controls and were not found to differ. Transferrin levels were significantly lower in the patients than in their controls but, conversely, the transferrin saturation was significantly higher in the patients. The results indicate that patients with Alzheimer's disease and Parkinson's disease have defective ceruloplasmin and SOD activities in common and that these defects are not necessarily associated with major disturbances in iron homeostasis.

  2. Kinetics of chlorite dismutase in a perchlorate degrading reactor sludge.

    Science.gov (United States)

    Nadaraja, Anupama Vijaya; Veetil, Prajeesh Gangadharan Puthiya; Vidyadharan, Athira; Bhaskaran, Krishnakumar

    2013-01-01

    Kinetics of chlorite dismutase (CD), the terminal enzyme involved in the perchlorate (ClO4(-)) reduction pathway, in a ClO4(-)-degrading bioreactor are reported in this study. Enzyme activity was determined from dissolved oxygen released during disproportionation of chlorite (ClO2(-)). CD activity was in the range 29.8-36.4 U/mg dry weight sludge, and kinetic constants Vmax and K(m) of the enzyme were 37.83 U/mg dry weight and 0.28 mM, respectively. Among reactor operational conditions, enzyme activity was observed at pH 4.0-9.0, with an optimum at pH 6.0. Redox potential in the range -50 to +120mV and NaCl up to 3.5 g/L had no significant effect on CD activity. However, co-occurring pollutants such as ammonium at 10 ppm, nitrite at 50 ppm and EDTA at 100 microM reduced CD activity substantially. The present study highlights ideal bioreactor conditions to avoid ClO2(-) toxicity, while indicating the buffering potential of a mixed microbial system against inhibiting factors to maintain stable CD activity in bioreactors.

  3. Data on the catalytic mechanism of thiol peroxidase mimics

    Directory of Open Access Journals (Sweden)

    B. Zadehvakili

    2016-09-01

    Full Text Available We have recently reported SAR data describing the pharmacological activity of a series of phenyl alkyl selenides and tellurides which catalyse the oxidation of thiols by hydrogen peroxide (H2O2, “The design of redox active thiol peroxidase mimics: dihydrolipoic acid recognition correlates with cytotoxicity and prooxidant action” B. Zadehvakili, S.M. McNeill, J.P. Fawcett, G.I. Giles (2016 [1]. This thiol peroxidase (TPx activity is potentially useful for a number of therapeutic applications, as it can alter the outcome of oxidative stress related pathologies and modify redox signalling. This article presents data describing the molecular changes that occur to a TPx mimic upon exposure to H2O2, and then the thiol mercaptoethanol, as characterised by UV–vis spectroscopy and HPLC retention time.

  4. Varroa destructor changes its cuticular hydrocarbons to mimic new hosts.

    Science.gov (United States)

    Le Conte, Y; Huang, Z Y; Roux, M; Zeng, Z J; Christidès, J-P; Bagnères, A-G

    2015-06-01

    Varroa destructor (Vd) is a honeybee ectoparasite. Its original host is the Asian honeybee, Apis cerana, but it has also become a severe, global threat to the European honeybee, Apis mellifera. Previous studies have shown that Varroa can mimic a host's cuticular hydrocarbons (HC), enabling the parasite to escape the hygienic behaviour of the host honeybees. By transferring mites between the two honeybee species, we further demonstrate that Vd is able to mimic the cuticular HC of a novel host species when artificially transferred to this new host. Mites originally from A. cerana are more efficient than mites from A. mellifera in mimicking HC of both A. cerana and A. mellifera. This remarkable adaptability may explain their relatively recent host-shift from A. cerana to A. mellifera.

  5. Wolff-Parkinson-White Syndrome Mimics a Conduction Disease

    OpenAIRE

    Marrakchi, S.; I. Kammoun; S. Kachboura

    2014-01-01

    Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old ...

  6. Molecular mechanical properties of short-sequence peptide enzyme mimics.

    Science.gov (United States)

    Takahashi, Tsukasa; Vo Ngo, Bao C; Xiao, Leyang; Arya, Gaurav; Heller, Michael J

    2016-01-01

    While considerable attempts have been made to recreate the high turnover rates of enzymes using synthetic enzyme mimics, most have failed and only a few have produced minimal reaction rates that can barely be considered catalytic. One particular approach we have focused on is the use of short-sequence peptides that contain key catalytic groups in close proximity. In this study, we designed six different peptides and tested their ability to mimic the catalytic mechanism of the cysteine proteases. Acetylation and deacylation by Ellman's Reagent trapping experiments showed the importance of having phenylalanine groups surrounding the catalytic sites in order to provide greater proximity between the cysteine, histidine, and aspartate amino acid R-groups. We have also carried out all-atom molecular dynamics simulations to determine the distance between these catalytic groups and the overall mechanical flexibility of the peptides. We found strong correlations between the magnitude of fluctuations in the Cys-His distance, which determines the flexibility and interactions between the cysteine thiol and histidine imidazole groups, and the deacylation rate. We found that, in general, shorter Cys-His distance fluctuations led to a higher deacylation rate constant, implying that greater confinement of the two residues will allow a higher frequency of the acetyl exchange between the cysteine thiol and histidine imidazole R-groups. This may be the key to future design of peptide structures with molecular mechanical properties that lead to viable enzyme mimics.

  7. Comparative analysis of cyanobacterial superoxide dismutases to discriminate canonical forms

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    Prabaharan Dharmar

    2007-11-01

    Full Text Available Abstract Background Superoxide dismutases (SOD are ubiquitous metalloenzymes that catalyze the disproportion of superoxide to peroxide and molecular oxygen through alternate oxidation and reduction of their metal ions. In general, SODs are classified into four forms by their catalytic metals namely; FeSOD, MnSOD, Cu/ZnSOD and NiSOD. In addition, a cambialistic form that uses Fe/Mn in its active site also exists. Cyanobacteria, the oxygen evolving photosynthetic prokaryotes, produce reactive oxygen species that can damage cellular components leading to cell death. Thus, the co-evolution of an antioxidant system was necessary for the survival of photosynthetic organisms with SOD as the initial enzyme evolved to alleviate the toxic effect. Cyanobacteria represent the first oxygenic photoautotrophs and their SOD sequences available in the databases lack clear annotation. Hence, the present study focuses on structure and sequence pattern of subsets of cyanobacterial superoxide dismutases. Result The sequence conservation and structural analysis of Fe (Thermosynechococcus elongatus BP1 and MnSOD (Anabaena sp. PCC7120 reveal the sharing of N and C terminal domains. At the C terminal domain, the metal binding motif in cyanoprokaryotes is DVWEHAYY while it is D-X-[WF]-E-H-[STA]-[FY]-[FY] in other pro- and eukaryotes. The cyanobacterial FeSOD differs from MnSOD at least in three ways viz. (i FeSOD has a metal specific signature F184X3A188Q189.......T280......F/Y303 while, in Mn it is R184X3G188G189......G280......W303, (ii aspartate ligand forms a hydrogen bond from the active site with the outer sphere residue of W243 in Fe where as it is Q262 in MnSOD; and (iii two unique lysine residues at positions 201 and 255 with a photosynthetic role, found only in FeSOD. Further, most of the cyanobacterial Mn metalloforms have a specific transmembrane hydrophobic pocket that distinguishes FeSOD from Mn isoform. Cyanobacterial Cu/ZnSOD has a copper domain and two

  8. Oxygen toxicity in Streptococcus mutans: manganese, iron and superoxide dismutase

    Energy Technology Data Exchange (ETDEWEB)

    Martin, M.E.; Strachan, R.C.; Aranha, H.; Evans, S.L.; Salin, M.L.; Welch, B.; Arceneaux, J.E.L.; Byers, B.R.

    1984-07-01

    When cultured anaerobically in a chemically defined medium that was treated with Chelex-100 to lower its trace metal content, Streptococcus mutans OMZ176 had no apparent requirement for manganese or iron. Manganese or iron was necessary for aerobic cultivation in deep static cultures. During continuous aerobic cultivation in a stirred chemostat, iron did not support the growth rate achieved with manganese. Since the dissolved oxygen level in the chemostat cultures was higher than the final level in the static cultures, manganese may be required for growth at elevated levels. In medium supplemented with manganese, cells grown anaerobically contained a low level of superoxide dismutase (SOD) activity; aerobic cultivation increased SOD activity at least threefold. In iron-supplemented medium, cells grown anaerobically also had low SOD activity; aerobic incubation resulted in little increase in SOD activity. Polyacrylamide gel electrophoresis of the cell extracts revealed a major band and a minor band of SOD activity in the cells grown with manganese; however, cells grown with iron contained a single band of SOD activity with an R/sub f/ value similar to that of the major band found in cells grown with manganese. None of the SOD activity bands were abolished by the inclusion of 2 mM hydrogen peroxide in the SOD activity strain. S. mutans may not produce a separate iron-containing SOD but may insert either iron or manganese into an apo-SOD protein. Alternatively, iron may function in another activity (not SOD) that augments the defense against oxygen toxicity at low SOD levels. 28 references, 3 figures, 1 table.

  9. A Manganese Superoxide Dismutase (SOD2)-Mediated Adaptive Response

    Science.gov (United States)

    Grdina, David J.; Murley, Jeffrey S.; Miller, Richard C.; Mauceri, Helena J.; Sutton, Harold G.; Thirman, Michael J.; Li, Jian Jian; Woloschak, Gayle E.; Weichselbaum, Ralph R.

    2013-01-01

    Very low doses of ionizing radiation, 5 to 100 mGy, can induce adaptive responses characterized by elevation in cell survival and reduction in micronuclei formation. Utilizing these end points, RKO human colon carcinoma and transformed mouse embryo fibroblasts (MEF), wild-type or knockout cells missing TNF receptors 1 and 2 (TNFR1−R2−), and C57BL/6 and TNFR1−R2− knockout mice, we demonstrate that intact TNF signaling is required for induction of elevated manganese superoxide dismutase (SOD2) activity (P adaptive responses when cells are challenged at a later time with 2 Gy. In contrast, amifostine’s free thiol form WR1065 can directly activate NF-κB giving rise to elevated SOD2 activity 24 h later and induce an adaptive response in both MEF wild-type and TNF signaling defective TNFR1−R2− cells. Transfection of cells with SOD2 siRNA completely abolishes both the elevation in SOD2 activity and expression of the adaptive responses. These results were confirmed in vivo using a micronucleus assay in splenocytes derived from C57BL/6 and TNFR1−R2− knockout mice that were exposed to 100 mGy or 400 mg/kg amifostine 24 h prior to exposure to a 2 Gy whole-body dose. A dose of 100 mGy also conferred enhanced protection to C57BL/6 mice exposed 24 h later to 100 mg/kg of N-Ethyl-N-nitrosourea (ENU). While very low radiation doses require an intact TNF signaling process to induce a SOD2-mediated adaptive response, amifostine can induce a similar adaptive response in both TNF receptor competent and knockout cells, respectively. PMID:23237540

  10. Expression of manganese superoxide dismutase in patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Shih-Meng Tsai

    2011-05-01

    Full Text Available Breast cancer has become the second leading cancer among females in Taiwan. Even though the etiology of breast cancer is multifactorial, oxidative stress plays an important role in the carcinogenesis. The purpose of this study was to investigate the expression of manganese superoxide dismutase (MnSOD, one of the major antioxidant enzymes that is involved against oxidative stress, in adjacent cancer-free breast tissues and neoplasm tissues within the same patient. Sixty-five breast cancer patients’ formalin-fixed tissue blocks, including ductal carcinoma in situ (DCIS tissues, invasive ductal carcinoma (IDC tissues, and adjacent cancer-free tissues, were evaluated by immunohistochemical stain. Meanwhile, their demographic and clinical information was also collected. The combined scores of MnSOD-positive cell proportion and MnSOD staining intensity were compared for different tissues within the same patient. The results showed that the mean combined scores of MnSOD expression in adjacent cancer-free tissues (6.33, IDC (5.30, and DCIS (3.78 were significantly different when assessed by repeated-measurement analysis of variance (F=14.17, p<0.001. Additionally, the results revealed that the distribution of strong MnSOD protein expression was 80.0%, 72.3%, and 52.3% in adjacent cancer-free tissues, IDC, and DCIS, respectively. However, there was no statistically significant relationship between the expression of MnSOD and grades of breast cancer or other clinicopathologic variables. We suggest that the expression of MnSOD in neoplasm tissues, independent of the clinicopathologic characters, plays a critical role in breast cancer biology.

  11. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

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    Jia Fang

    2016-01-01

    Conclusions: The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

  12. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    Science.gov (United States)

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  13. Bicelles and Other Membrane Mimics: Comparison of Structure, Properties, and Dynamics from MD Simulations

    DEFF Research Database (Denmark)

    Vestergaard, Mikkel; Kraft, Johan Frederik; Vosegaard, Thomas

    2015-01-01

    The increased interest in studying membrane proteins has led to the development of new membrane mimics such as bicelles and nanodiscs. However, only limited knowledge is available of how these membrane mimics are affected by embedded proteins and how well they mimic a lipid bilayer. Herein, we pr...

  14. Study on the relationship between endometrial carcinoma and serum levels of malondialdehyde and superoxide dismutase

    Institute of Scientific and Technical Information of China (English)

    Zhang Ping; Dai Hong-ying

    2008-01-01

    Objective:To study the relationship of human endometrial carcinoma and the serum levels of malondialdehyde and superoxide dismutase.Methods:The serum levels of malondialdehyde(MDA),total superoxide dismutase(T-SOD),CuZn-superox-ide dismutase(CuZn-SOD),Mn-superoxide dismutase(Mn-SOD)were measured in 37 women with endometrlal carcinoma(study group)and 40 healthy women(control group).The relationship between surgical-pathological smiling of the tumor and these parameters was analyzed.Results:(1)The serum levels of MDA were significantly higher in study group than in control group(P0.05);(3)There was a positive correlation between surgical-patholological staging and the level of MDA(r=0.9206,P0.05).Conclusion:The psthogenesis and development of endometrial carcinoma may be associated with the imbalance of oxidation and antioxidetion.

  15. Unexpected Diversity of Chlorite Dismutases: a Catalytically Efficient Dimeric Enzyme from Nitrobacter winogradskyi ▿ †

    OpenAIRE

    Mlynek, Georg; Sjöblom, Björn; Kostan, Julius; Füreder, Stephanie; Maixner, Frank; Gysel, Kira; Furtmüller, Paul Georg; Obinger, Christian; Wagner, Michael; Daims, Holger; Djinović-Carugo, Kristina

    2011-01-01

    Chlorite dismutase (Cld) is a unique heme enzyme catalyzing the conversion of ClO2− to Cl− and O2. Cld is usually found in perchlorate- or chlorate-reducing bacteria but was also recently identified in a nitrite-oxidizing bacterium of the genus Nitrospira. Here we characterized a novel Cld-like protein from the chemolithoautotrophic nitrite oxidizer Nitrobacter winogradskyi which is significantly smaller than all previously known chlorite dismutases. Its three-dimensional (3D) crystal structu...

  16. Water soluble azido polyisocyanopeptides as functional β-sheet mimics

    NARCIS (Netherlands)

    Schwartz, Erik; Koepf, Matthieu; Kitto, Heather J.; Espelt, Mónica; Nebot-Carda, Vicent J.; Gelder, de Rene; Nolte, Roeland J.M.; Cornelissen, Jeroen J.L.M.; Rowan, Alan E.

    2009-01-01

    The design and synthesis of functional biomimetic water soluble polymers with a defined secondary structure has been developed using β-sheet polyisocyanopeptide scaffolds. Water soluble isocyanopolymers were prepared by random copolymerisation of the azido functionalized isocyanopeptides with nonfun

  17. Astrocyte-neuron co-culture on microchips based on the model of SOD mutation to mimic ALS.

    Science.gov (United States)

    Kunze, Anja; Lengacher, Sylvain; Dirren, Elisabeth; Aebischer, Patrick; Magistretti, Pierre J; Renaud, Philippe

    2013-07-24

    Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. ALS is believed to be a non-cell autonomous condition, as other cell types, including astrocytes, have been implicated in disease pathogenesis. Hence, to facilitate the development of therapeutics against ALS, it is crucial to better understand the interactions between astrocytes and neural cells. Furthermore, cell culture assays are needed that mimic the complexity of cell to cell communication at the same time as they provide control over the different microenvironmental parameters. Here, we aim to validate a previously developed microfluidic system for an astrocyte-neuron cell culture platform, in which astrocytes have been genetically modified to overexpress either a human wild-type (WT) or a mutated form of the super oxide dismutase enzyme 1 (SOD1). Cortical neural cells were co-cultured with infected astrocytes and studied for up to two weeks. Using our microfluidic device that prevents direct cell to cell contact, we could evaluate neural cell response in the vicinity of astrocytes. We showed that neuronal cell density was reduced by about 45% when neurons were co-cultured with SOD-mutant astrocytes. Moreover, we demonstrated that SOD-WT overexpressing astrocytes reduced oxidative stress on cortical neurons that were in close metabolic contact. In contrast, cortical neurons in metabolic contact with SOD-mutant astrocytes lost their synapsin protein expression after severe glutamate treatment, an indication of the toxicity potentiating effect of the SOD-mutant enzyme.

  18. De novo design of protein mimics of B-DNA.

    Science.gov (United States)

    Yüksel, Deniz; Bianco, Piero R; Kumar, Krishna

    2016-01-01

    Structural mimicry of DNA is utilized in nature as a strategy to evade molecular defences mounted by host organisms. One such example is the protein Ocr - the first translation product to be expressed as the bacteriophage T7 infects E. coli. The structure of Ocr reveals an intricate and deliberate arrangement of negative charges that endows it with the ability to mimic ∼24 base pair stretches of B-DNA. This uncanny resemblance to DNA enables Ocr to compete in binding the type I restriction modification (R/M) system, and neutralizes the threat of hydrolytic cleavage of viral genomic material. Here, we report the de novo design and biophysical characterization of DNA mimicking peptides, and describe the inhibitory action of the designed helical bundles on a type I R/M enzyme, EcoR124I. This work validates the use of charge patterning as a design principle for creation of protein mimics of DNA, and serves as a starting point for development of therapeutic peptide inhibitors against human pathogens that employ molecular camouflage as part of their invasion stratagem.

  19. Wolff-Parkinson-White Syndrome Mimics a Conduction Disease

    Directory of Open Access Journals (Sweden)

    S. Marrakchi

    2014-01-01

    Full Text Available Background. It is important to recognise Wolff-Parkinson-White (WPW syndrome in electrocardiograms (ECG, as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a “false positive” of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope.

  20. Genomic responses in mouse models poorly mimic human inflammatory diseases.

    Science.gov (United States)

    Seok, Junhee; Warren, H Shaw; Cuenca, Alex G; Mindrinos, Michael N; Baker, Henry V; Xu, Weihong; Richards, Daniel R; McDonald-Smith, Grace P; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C; López, Cecilia M; Honari, Shari; Moore, Ernest E; Minei, Joseph P; Cuschieri, Joseph; Bankey, Paul E; Johnson, Jeffrey L; Sperry, Jason; Nathens, Avery B; Billiar, Timothy R; West, Michael A; Jeschke, Marc G; Klein, Matthew B; Gamelli, Richard L; Gibran, Nicole S; Brownstein, Bernard H; Miller-Graziano, Carol; Calvano, Steve E; Mason, Philip H; Cobb, J Perren; Rahme, Laurence G; Lowry, Stephen F; Maier, Ronald V; Moldawer, Lyle L; Herndon, David N; Davis, Ronald W; Xiao, Wenzhong; Tompkins, Ronald G

    2013-02-26

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

  1. A Photoisomerizing Rhodopsin Mimic Observed at Atomic Resolution.

    Science.gov (United States)

    Nosrati, Meisam; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James H

    2016-07-20

    The members of the rhodopsin family of proteins are involved in many essential light-dependent processes in biology. Specific photoisomerization of the protein-bound retinylidene PSB at a specified wavelength range of light is at the heart of all of these systems. Nonetheless, it has been difficult to reproduce in an engineered system. We have developed rhodopsin mimics, using intracellular lipid binding protein family members as scaffolds, to study fundamental aspects of protein/chromophore interactions. Herein we describe a system that specifically isomerizes the retinylidene protonated Schiff base both thermally and photochemically. This isomerization has been characterized at atomic resolution by quantitatively interconverting the isomers in the crystal both thermally and photochemically. This event is accompanied by a large pKa change of the imine similar to the pKa changes observed in bacteriorhodopsin and visual opsins during isomerization.

  2. Constraining cyclic peptides to mimic protein structure motifs

    DEFF Research Database (Denmark)

    Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik;

    2014-01-01

    Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well-defined three-dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable...... protein-like structures in water. However, short peptides can be induced to fold into protein-like bioactive conformations (strands, helices, turns) by cyclization, in conjunction with the use of other molecular constraints, that helps to fine-tune three-dimensional structure. Such constrained cyclic...... peptides can have protein-like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three-dimensional structures of strand, turn or helical segments of peptides...

  3. Amyloid protein unfolding and insertion kinetics on neuronal membrane mimics

    Science.gov (United States)

    Qiu, Liming; Buie, Creighton; Vaughn, Mark; Cheng, Kwan

    2010-03-01

    Atomistic details of beta-amyloid (Aβ ) protein unfolding and lipid interaction kinetics mediated by the neuronal membrane surface are important for developing new therapeutic strategies to prevent and cure Alzheimer's disease. Using all-atom MD simulations, we explored the early unfolding and insertion kinetics of 40 and 42 residue long Aβ in binary lipid mixtures with and without cholesterol that mimic the cholesterol-depleted and cholesterol-enriched lipid nanodomains of neurons. The protein conformational transition kinetics was evaluated from the secondary structure profile versus simulation time plot. The extent of membrane disruption was examined by the calculated order parameters of lipid acyl chains and cholesterol fused rings as well as the density profiles of water and lipid headgroups at defined regions across the lipid bilayer from our simulations. Our results revealed that both the cholesterol content and the length of the protein affect the protein-insertion and membrane stability in our model lipid bilayer systems.

  4. Spinal dural arteriovenous fistula: Imaging features and its mimics

    Energy Technology Data Exchange (ETDEWEB)

    Jeog, Ying; Ting, David Yen; Hsu, Hui Ling; Huang, Yen Lin; Chen, Chi Jen; Tseng, Ting Chi [Dept. of Radiology, aipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan (China)

    2015-10-15

    Spinal dural arteriovenous fistula (SDAVF) is the most common spinal vascular malformation, however it is still rare and underdiagnosed. Magnetic resonance imaging findings such as spinal cord edema and dilated and tortuous perimedullary veins play a pivotal role in the confirmation of the diagnosis. However, spinal angiography remains the gold standard in the diagnosis of SDAVF. Classic angiographic findings of SDAVF are early filling of radicular veins, delayed venous return, and an extensive network of dilated perimedullary venous plexus. A series of angiograms of SDAVF at different locations along the spinal column, and mimics of serpentine perimedullary venous plexus on MR images, are demonstrated. Thorough knowledge of SDAVF aids correct diagnosis and prevents irreversible complications.

  5. Genomic responses in mouse models poorly mimic human inflammatory diseases

    Science.gov (United States)

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  6. Piezoelectric materials mimic the function of the cochlear sensory epithelium

    Science.gov (United States)

    Inaoka, Takatoshi; Shintaku, Hirofumi; Nakagawa, Takayuki; Kawano, Satoyuki; Ogita, Hideaki; Sakamoto, Tatsunori; Hamanishi, Shinji; Wada, Hiroshi; Ito, Juichi

    2011-01-01

    Cochlear hair cells convert sound vibration into electrical potential, and loss of these cells diminishes auditory function. In response to mechanical stimuli, piezoelectric materials generate electricity, suggesting that they could be used in place of hair cells to create an artificial cochlear epithelium. Here, we report that a piezoelectric membrane generated electrical potentials in response to sound stimuli that were able to induce auditory brainstem responses in deafened guinea pigs, indicating its capacity to mimic basilar membrane function. In addition, sound stimuli were transmitted through the external auditory canal to a piezoelectric membrane implanted in the cochlea, inducing it to vibrate. The application of sound to the middle ear ossicle induced voltage output from the implanted piezoelectric membrane. These findings establish the fundamental principles for the development of hearing devices using piezoelectric materials, although there are many problems to be overcome before practical application. PMID:22025702

  7. Biofilm streamer formation in a microfluidic porous media mimic

    Science.gov (United States)

    Kumar, Aloke; Valiei, Amin; Mukherjee, Partha; Liu, Yang; Thundat, Thomas

    2013-03-01

    Biofilm formation in porous media is of significant importance in many environmental and industrial processes such as bioremediation, oil recovery, and wastewater treatment. Among different biological and environmental factors, hydrodynamics is considered an important determinant of the dynamics of biofilm formation. In the present study, we fabricated a microfluidic porous media mimic and investigated how fluid flow influences the formation of filamentous structures, known as streamers, between porous media structures. Streamers are viscoelastic materials composed of extracellular polymeric substances (EPS) and bacterial cells, and these filamentous structures are typically tethered at either one of both ends to surfaces. We studied evolution of streamers in different flow rates and identified a tangible link between hydrodynamic conditions and development of these filamentous structures. Our results show that hydrodynamic conditions not only determine the limit of the streamers formation, but also influence both temporal evolution and spatial organization of biofilm streamers.

  8. Malakoplakia mimics urinary bladder cancer: A case report

    Directory of Open Access Journals (Sweden)

    Ristić-Petrović Ana

    2013-01-01

    Full Text Available Introduction. Malakoplakia is an unusual and very rare chronic inflammatory disease. In bladder especially it can mimic malignancy and lead to serious misdiagnosis. Case report. We presented a case of a middle-aged woman with persistent macrohematuria and cystoscopically polypoid bladder mass that resembled a neoplastic process. The final diagnosis was based on cystoscopic biopsy and microscopic findings of acidophilic, foamy histiocytes with the presence of Michaelis-Gutmann inclusions which are characteristic for diagnosis of malakoplakia. Immunohistochemistry confirmed diagnosis by demonstrating CD68-positive macrophages. Conclusion. Urinary bladder malakoplakia should be considered in patients with persistent urinary tract infections and tumor mass at cystoscopy. Early identification with prompt antibiotic treatment can be helpful in avoiding unnecessary surgical interventions and in preventing development of possible complications. [Projekat Ministarstva nauke Republike Srbije, br. 175092

  9. Restless legs syndrome in Wilson's disease: frequency, characteristics, and mimics.

    Science.gov (United States)

    Trindade, M C; Bittencourt, T; Lorenzi-Filho, G; Alves, R C; de Andrade, D C; Fonoff, E T; Bor-Seng-Shu, E; Machado, A A; Teixeira, M J; Barbosa, E R; Tribl, G G

    2017-02-01

    To determine characteristics, clinical significance, frequency, and mimics of restless legs syndrome (RLS) in a cohort of Wilson's disease (WD, n = 42/f = 18), compared to healthy, matched controls. Structured clinical interviews (patients and caregiving family members), repeated neurological examinations (afternoon and presleep), comprehensive laboratory tests, WD-, RLS-, and sleep-specific rating scales, and video-polysomnography. Thirteen patients with WD (13/42 = 31.0%) clearly fulfilled the five diagnostic criteria of RLS; in eight patients (19.1%), the burden of RLS was clinically significant. The RLS was of moderate severity, equally distributed among sexes, manifested mainly in the evening and before falling asleep, and had developed mostly after clinical manifestation of WD (time elapsed 10.2 ± 14.5 years), still at a young mean age (27.5 ± 11.5 years). The known RLS-associated features were absent (normal iron and kidney parameters) or rare (positive family history, polyneuropathy). Compared to WD patients without RLS, patients with RLS were significantly elder and had suffered longer from WD. WD-specific RLS mimics as well as RLS confounding motor comorbidities (dystonia, tremor, chorea) were frequent and a diagnostic challenge; in difficult cases, the differentiation was reached by clinical observation of the motor behavior in the evening or at nighttime. RLS was frequent in this cohort of WD and might be causally related to WD. RLS should be included in the diagnostic work-up of WD. In complex motor disorders, differential diagnosis of RLS might require evening/nighttime examination and video-polysomnography. In WD patients with a clinically significant RLS, treatment with dopaminergic substances may be considered. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Decrease of reactive oxygen species-related biomarkers in the tissue-mimic 3D spheroid culture of human lung cells exposed to zinc oxide nanoparticles.

    Science.gov (United States)

    Kim, Eunjoo; Jeon, Won Bae; Kim, Soonhyun; Lee, Soo-Keun

    2014-05-01

    Common 2-dimensional (2D) cell cultures do not adequately represent cell-cell and cell-matrix signaling and substantially different diffusion/transport pathways. To obtain tissue-mimic information on nanoparticle toxicity from in vitro cell tests, we used a 3-dimensional (3D) culture of human lung cells (A549) prepared with elastin-like peptides modified with an arginine-glycine-aspartate motif. The 3D cells showed different cellular phenotypes, gene expression profiles, and functionalities compared to the 2D cultured cells. In gene array analysis, 3D cells displayed the induced extracellular matrix (ECM)-related biological functions such as cell-to-cell signaling and interaction, cellular function and maintenance, connective tissue development and function, molecular transport, and tissue morphology. Additionally, the expression of ECM-related molecules, such as laminin, fibronectin, and insulin-like growth factor binding protein 3 (IGFBP3), was simultaneously induced at both mRNA and protein levels. When 0.08-50 microg/ml zinc oxide nanoparticles (ZnO-NPs) were administered to 2D and 3D cells, the cell proliferation was not significantly changed. The level of molecular markers for oxidative stress, such as superoxide dismutase (SOD), Bcl-2, ATP synthase, and Complex IV (cytochrome C oxidase), was significantly reduced in 2D culture when exposed to 10 microg/ml ZnO-NPs, but no significant decrease was detected in 3D culture when exposed to the same concentration of ZnO-NPs. In conclusion, the tissue-mimic phenotype and functionality of 3D cells could be achieved through the elevated expression of ECM components. The 3D cells were expected to help to better predict the nanotoxicity of ZnO-NPs at tissue-level by increased cell-cell and cell-ECM adhesion and signaling. The tissue-mimic morphology would also be useful to simulate the diffusion/transport of the nanoparticles in vitro.

  11. All-metal clusters that mimic the chemistry of halogens.

    Science.gov (United States)

    Zhao, Tianshan; Li, Yawei; Wang, Qian; Jena, Puru

    2013-10-07

    Owing to their s(2)p(5) electronic configuration, halogen atoms are highly electronegative and constitute the anionic components of salts. Whereas clusters that contain no halogen atoms, such as AlH(4), mimic the chemistry of halogens and readily form salts (e.g., Na(+)(AlH(4))(-)), clusters that are solely composed of metal atoms and yet behave in the same manner as a halogen are rare. Because coinage-metal atoms (Cu, Ag, and Au) only have one valence electron in their outermost electronic shell, as in H, we examined the possibility that, on interacting with Al, in particular as AlX(4) (X=Cu, Ag, Au), these metal atoms may exhibit halogen-like properties. By using density functional theory, we show that AlAu(4) not only mimics the chemistry of halogens, but also, with a vertical detachment energy (VDE) of 3.98 eV in its anionic form, is a superhalogen. Similarly, analogous to XHX superhalogens (X=F, Cl, Br), XAuX species with VDEs of 4.65, 4.50, and 4.34 eV in their anionic form, respectively, also form superhalogens. In addition, Au can also form hyperhalogens, a recently discovered species that show electron affinities (EAs) that are even higher than those of their corresponding superhalogen building blocks. For example, the VDEs of M(AlAu(4))(2)(-) (M=Na and K) and anionic (FAuF)Au(FAuF) range from 4.06 to 5.70 eV. Au-based superhalogen anions, such as AlAu(4)(-) and AuF(2)(-), have the additional advantage that they exhibit wider optical absorption ranges than their H-based analogues, AlH(4)(-) and HF(2)(-). Because of the catalytic properties and the biocompatibility of Au, Au-based superhalogens may be multifunctional. However, similar studies that were carried out for Cu and Ag atoms have shown that, unlike AlAu(4), AlX(4) (X=Cu, Ag) clusters are not superhalogens, a property that can be attributed to the large EA of the Au atom. Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Expression, purification and molecular modeling of iron-containing superoxide dismutase from Acidithiobacillus ferrooxidans

    Institute of Scientific and Technical Information of China (English)

    LIU Yuan-dong; GAO Jian; QIU Guan-zhou; LIU Xue-duan; ZHANG Cheng-gui; OUYANG Xu-dong; JIANG Ying; ZENG Jia

    2008-01-01

    The superoxide dismutase(SOD) from Acidithiobacillus ferrooxidans may play an important role in its tolerance to the extremely toxic and oxidative environment of bioleaching.This gene was cloned and then successfully expressed in Escherichia coli.The expressed protein was finally purified by one-step affinity chromatography to homogeneity and observed to be dimer according to SDS-PAGE and MALDI-TOF-MS.The metal content determination and optical spectra results of the recombinant protein confirmed that the protein was an iron-containing superoxide dismutase.Molecular modeling for the protein revealed that the iron atom was ligated by His26,His75,Asp158 and His162.

  13. THE ZN-SITE IN BOVINE COPPER, ZINC SUPEROXIDE-DISMUTASE STUDIED BY CD-111 PAC

    DEFF Research Database (Denmark)

    Kofod, Pauli; Bjerrum, Morten J.; Bauer, Rogert

    1991-01-01

    The active site in bovine copper, zinc superoxide dismutase (Cu2. Zn2 SOD) has been studied by 111Cd time differential Perturbed Angular Correlation (PAC) on enzyme with Zn2+ replaced by excited 'Cd2+. The PAC spectra obtained for both the oxidized and the reduced form of Cu2Cd2SOD show no asymme......The active site in bovine copper, zinc superoxide dismutase (Cu2. Zn2 SOD) has been studied by 111Cd time differential Perturbed Angular Correlation (PAC) on enzyme with Zn2+ replaced by excited 'Cd2+. The PAC spectra obtained for both the oxidized and the reduced form of Cu2Cd2SOD show...

  14. Superoxide dismutase type 1 in monocytes of chronic kidney disease patients

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Krueger, Katharina; Diedrich, Madeleine

    2011-01-01

    We analyzed proteomic profiles in monocytes of chronic kidney disease (CKD) patients and healthy control subjects. Two-dimensional electrophoresis (2-DE) and silver staining indicated differences in protein pattern. Among the analyzed proteins, superoxide dismutase type 1 (SOD1), which was identi......We analyzed proteomic profiles in monocytes of chronic kidney disease (CKD) patients and healthy control subjects. Two-dimensional electrophoresis (2-DE) and silver staining indicated differences in protein pattern. Among the analyzed proteins, superoxide dismutase type 1 (SOD1), which...

  15. Superoxide anion production and superoxide dismutase and catalase activities in Coxiella burnetii.

    OpenAIRE

    Akporiaye, E T; Baca, O G

    1983-01-01

    Coxiella burnetii was examined for superoxide anion (O2-) production and superoxide dismutase and catalase activities. The organism generated O2- at pH 4.5 but not at pH 7.4. The rickettsia displayed superoxide dismutase activity distinguishable from that of the host cell (L-929 mouse fibroblast). Catalase activity was maximal at pH 7.0 and diminished at pH 4.5. These enzymes may account, in part, for the ability of this obligate intracellular parasite to survive within phagocytes.

  16. A Case Report of Neurosarcoidosis Presenting as a Lymphoma Mimic

    Science.gov (United States)

    Cameron, Lauren; Syritsyna, Olga

    2016-01-01

    Objective. To describe a unique presentation of neurosarcoidosis. Background. Central nervous system involvement is rare in sarcoidosis. Sarcoidosis can be severe and can be mistaken for systemic lymphoma. Case Description. A 55-year-old right-handed white male with past medical history of obstructive sleep apnea, Raynaud's disease, and Hashimoto's thyroiditis was noted to have cognitive decline over a duration of few weeks and 20 lb weight loss. His neurologic exam (including cranial nerves) was normal except for five-minute recall. Head CT revealed a lacrimal gland mass, confirmed on brain MRI, which was suspicious for lymphoma on brain PET/MRI. Subsequent whole-body FDG PET/CT scan showed multiple enlarged lymph nodes. Bone marrow biopsy was negative. Serum and CSF ACE levels were within normal limits. Supraclavicular lymph node biopsy before steroids therapy was initiated and revealed multiple noncaseating granulomas, diagnostic of “sarcoidosis.” He was treated with daily prednisone for two months, followed by weekly infliximab. Brain MRI two months after treatment with prednisone showed decrease in size of lacrimal lesion, and brain PET/MRI showed normal brain metabolism pattern after five months. Neurocognitive evaluation three months after diagnosis demonstrated improvements in memory abilities. Discussion. Both clinically and radiographically, neurosarcoidosis can mimic systemic lymphoma. Biopsy in these types of cases is necessary to establish the diagnosis. PMID:27800198

  17. Chimpanzees and humans mimic pupil-size of conspecifics.

    Science.gov (United States)

    Kret, Mariska E; Tomonaga, Masaki; Matsuzawa, Tetsuro

    2014-01-01

    Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes). We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals.

  18. Young diabetics' compliance in the framework of the MIMIC model.

    Science.gov (United States)

    Kyngäs, H; Hentinen, M; Koivukangas, P; Ohinmaa, A

    1996-11-01

    The compliance of 346 young diabetics aged 13-17 years with health regimens is analysed in the framework of a MIMIC (multiple indicators, multiple causes) model. The data were compiled by means of a questionnaire on compliance, conditions for compliance, the meaning attached to treatment and the impact of the disease, and the model constructed using the LISREL VII programme, treating compliance as an unobserved variable formulated in terms of observed causes (x-variables) and observed indicators (y-variables). The resulting solutions are entirely satisfactory. The goodness-of-fit index is 0.983, the root mean square residual 0.058 and the chi-squared statistic 43.35 (P compliance to be indicated by self-care behaviour, responsibility for treatment, intention to pursue the treatment and collaboration with the physician, and to be greatly determined by motivation, experience of the results of treatment and having the energy and will-power to pursue the treatment and, to a lesser extent, by a sense of normality and fear.

  19. Approaches to mimic the metallic sheen in beetles

    Science.gov (United States)

    Lenau, Torben A.; Aggerbeck, Martin; Nielsen, Steffen

    2009-08-01

    A range of different beetles exhibits brilliant colours and metallic sheen. One of the most spectacular species is the Plusiotis resplendens from Central America with gold metal appearance. The beetle shells are made from chitin and have a number of unique properties that apart from spectacular aesthetic effects include metal sheen from non-metal surfaces combined with electric and thermal insulation. The reflection mechanism has been studied by a number of authors and is well understood. Basically there are 2 different reflection principles. One is the multilayer reflector where alternating layers have high and low refractive index. The other is the Bouligand structure where birefringent chiral nanofibres are organised in spiral structures. The paper describes work done to explore different approaches to mimic these structures using polymer based materials and production methods that are suitable for more complex double curved geometry. One approach is to use alternating layers of 2 different polymers applied by dipping and another is applying cholesteric liquid crystals in paint. However, none of them can yet make the desired metal-looking free-form surfaces.

  20. Reproducing Natural Spider Silks’ Copolymer Behavior in Synthetic Silk Mimics

    Science.gov (United States)

    An, Bo; Jenkins, Janelle E.; Sampath, Sujatha; Holland, Gregory P.; Hinman, Mike; Yarger, Jeffery L.; Lewis, Randolph

    2012-01-01

    Dragline silk from orb-weaving spiders is a copolymer of two large proteins, major ampullate spidroin 1 (MaSp1) and 2 (MaSp2). The ratio of these proteins is known to have a large variation across different species of orb-weaving spiders. NMR results from gland material of two different species of spiders, N. clavipes and A. aurantia, indicates that MaSp1 proteins are more easily formed into β-sheet nanostructures, while MaSp2 proteins form random coil and helical structures. To test if this behavior of natural silk proteins could be reproduced by recombinantly produced spider silk mimic protein, recombinant MaSp1/MaSp2 mixed fibers as well as chimeric silk fibers from MaSp1 and MaSp2 sequences in a single protein were produced based on the variable ratio and conserved motifs of MaSp1 and MaSp2 in native silk fiber. Mechanical properties, solid-state NMR, and XRD results of tested synthetic fibers indicate the differing roles of MaSp1 and MaSp2 in the fiber and verify the importance of postspin stretching treatment in helping the fiber to form the proper spatial structure. PMID:23110450

  1. Reproducing natural spider silks' copolymer behavior in synthetic silk mimics.

    Science.gov (United States)

    An, Bo; Jenkins, Janelle E; Sampath, Sujatha; Holland, Gregory P; Hinman, Mike; Yarger, Jeffery L; Lewis, Randolph

    2012-12-10

    Dragline silk from orb-weaving spiders is a copolymer of two large proteins, major ampullate spidroin 1 (MaSp1) and 2 (MaSp2). The ratio of these proteins is known to have a large variation across different species of orb-weaving spiders. NMR results from gland material of two different species of spiders, N. clavipes and A. aurantia , indicates that MaSp1 proteins are more easily formed into β-sheet nanostructures, while MaSp2 proteins form random coil and helical structures. To test if this behavior of natural silk proteins could be reproduced by recombinantly produced spider silk mimic protein, recombinant MaSp1/MaSp2 mixed fibers as well as chimeric silk fibers from MaSp1 and MaSp2 sequences in a single protein were produced based on the variable ratio and conserved motifs of MaSp1 and MaSp2 in native silk fiber. Mechanical properties, solid-state NMR, and XRD results of tested synthetic fibers indicate the differing roles of MaSp1 and MaSp2 in the fiber and verify the importance of postspin stretching treatment in helping the fiber to form the proper spatial structure.

  2. Antimicrobial polymers as synthetic mimics of host-defense peptides.

    Science.gov (United States)

    Kuroda, Kenichi; Caputo, Gregory A

    2013-01-01

    Antibiotic-resistant bacteria 'superbugs' are an emerging threat to public health due to the decrease in effective antibiotics as well as the slowed pace of development of new antibiotics to replace those that become ineffective. The need for new antimicrobial agents is a well-documented issue relating to world health. Tremendous efforts have been given to developing compounds that not only show high efficacy, but also those that are less susceptible to resistance development in the bacteria. However, the development of newer, stronger antibiotics which can overcome these acquired resistances is still a scientific challenge because a new mode of antimicrobial action is likely required. To that end, amphiphilic, cationic polymers have emerged as a promising candidate for further development as an antimicrobial agent with decreased potential for resistance development. These polymers are designed to mimic naturally occurring host-defense antimicrobial peptides which act on bacterial cell walls or membranes. Antimicrobial-peptide mimetic polymers display antibacterial activity against a broad spectrum of bacteria including drug-resistant strains and are less susceptible to resistance development in bacteria. These polymers also showed selective activity to bacteria over mammalian cells. Antimicrobial polymers provide a new molecular framework for chemical modification and adaptation to tune their biological functions. The peptide-mimetic design of antimicrobial polymers will be versatile, generating a new generation of antibiotics toward implementation of polymers in biomedical applications. Copyright © 2012 Wiley Periodicals, Inc.

  3. Chimpanzees and humans mimic pupil-size of conspecifics.

    Directory of Open Access Journals (Sweden)

    Mariska E Kret

    Full Text Available Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes. We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals.

  4. Small Undifferentiated Pancreatic Adenocarcinoma which Mimics IPMN at Imaging

    Directory of Open Access Journals (Sweden)

    Mirko D’Onofrio

    2009-07-01

    Full Text Available Context To present the case of an unusual presentation at imaging of a very small solid undifferentiated pancreatic adenocarcinoma which mimics a side-branch intraductal papillary mucinous neoplasm. Case report The patient came to our hospital for a revaluation of a cystic pancreatic lesion. Ultrasound (US and contrast-enhanced ultrasound (CEUS examinations were carried out. A small cystic lesion of about 1.5 cm in diameter was seen in the posterior aspect of the pancreatic uncinate process A very small, solid, vascularized nodule was detected at CEUS within the lesion. Consequently, the patient underwent CT and MRI. MRI confirmed the presence of an intralesional nodule and communication with the main pancreatic duct was demonstrated, suggesting the diagnosis of intraductal papillary mucinous neoplasm with solid intralesional tissue. A pylorus preserving pancreaticoduodenectomy was carried out. An undifferentiated adenocarcinoma having a notable peripheral inflammatory reaction and dilated branch duct was finally diagnosed. Conclusion To our knowledge, we present for the first time, the case of a very small solid undifferentiated pancreatic adenocarcinoma of the uncinate process which mimicked a side-branch intraductal papillary mucinous neoplasm at imaging. The cystic appearance may be an epiphenomenon of a solid lesion and this possibility has to be considered when one encounters incidental cystic lesions at imaging.

  5. A Case Report of Neurosarcoidosis Presenting as a Lymphoma Mimic

    Directory of Open Access Journals (Sweden)

    Gurcharanjeet Kaur

    2016-01-01

    Full Text Available Objective. To describe a unique presentation of neurosarcoidosis. Background. Central nervous system involvement is rare in sarcoidosis. Sarcoidosis can be severe and can be mistaken for systemic lymphoma. Case Description. A 55-year-old right-handed white male with past medical history of obstructive sleep apnea, Raynaud’s disease, and Hashimoto’s thyroiditis was noted to have cognitive decline over a duration of few weeks and 20 lb weight loss. His neurologic exam (including cranial nerves was normal except for five-minute recall. Head CT revealed a lacrimal gland mass, confirmed on brain MRI, which was suspicious for lymphoma on brain PET/MRI. Subsequent whole-body FDG PET/CT scan showed multiple enlarged lymph nodes. Bone marrow biopsy was negative. Serum and CSF ACE levels were within normal limits. Supraclavicular lymph node biopsy before steroids therapy was initiated and revealed multiple noncaseating granulomas, diagnostic of “sarcoidosis.” He was treated with daily prednisone for two months, followed by weekly infliximab. Brain MRI two months after treatment with prednisone showed decrease in size of lacrimal lesion, and brain PET/MRI showed normal brain metabolism pattern after five months. Neurocognitive evaluation three months after diagnosis demonstrated improvements in memory abilities. Discussion. Both clinically and radiographically, neurosarcoidosis can mimic systemic lymphoma. Biopsy in these types of cases is necessary to establish the diagnosis.

  6. Non-canonical roles of tRNAs and tRNA mimics in bacterial cell biology.

    Science.gov (United States)

    Katz, Assaf; Elgamal, Sara; Rajkovic, Andrei; Ibba, Michael

    2016-08-01

    Transfer RNAs (tRNAs) are the macromolecules that transfer activated amino acids from aminoacyl-tRNA synthetases to the ribosome, where they are used for the mRNA guided synthesis of proteins. Transfer RNAs are ancient molecules, perhaps even predating the existence of the translation machinery. Albeit old, these molecules are tremendously conserved, a characteristic that is well illustrated by the fact that some bacterial tRNAs are efficient and specific substrates of eukaryotic aminoacyl-tRNA synthetases and ribosomes. Considering their ancient origin and high structural conservation, it is not surprising that tRNAs have been hijacked during evolution for functions outside of translation. These roles beyond translation include synthetic, regulatory and information functions within the cell. Here we provide an overview of the non-canonical roles of tRNAs and their mimics in bacteria, and discuss some of the common themes that arise when comparing these different functions.

  7. A common theme in extracellular fluids of beetles: extracellular superoxide dismutases crucial for balancing ROS in response to microbial challenge

    Science.gov (United States)

    Gretscher, René R.; Streicher, Priska E.; Strauß, Anja S.; Wielsch, Natalie; Stock, Magdalena; Wang, Ding; Boland, Wilhelm; Burse, Antje

    2016-01-01

    Extracellular Cu/Zn superoxide dismutases (SODs) are critical for balancing the level of reactive oxygen species in the extracellular matrix of eukaryotes. In the present study we have detected constitutive SOD activity in the haemolymph and defensive secretions of different leaf beetle species. Exemplarily, we have chosen the mustard leaf beetle, Phaedon cochleariae, as representative model organism to investigate the role of extracellular SODs in antimicrobial defence. Qualitative and quantitative proteome analyses resulted in the identification of two extracellular Cu/Zn SODs in the haemolymph and one in the defensive secretions of juvenile P. cochleariae. Furthermore, quantitative expression studies indicated fat body tissue and defensive glands as the main synthesis sites of these SODs. Silencing of the two SODs revealed one of them, PcSOD3.1, as the only relevant enzyme facilitating SOD activity in haemolymph and defensive secretions in vivo. Upon challenge with the entomopathogenic fungus, Metarhizium anisopliae, PcSOD3.1-deficient larvae exhibited a significantly higher mortality compared to other SOD-silenced groups. Hence, our results serve as a basis for further research on SOD regulated host-pathogen interactions. In defensive secretions PcSOD3.1-silencing affected neither deterrent production nor activity against fungal growth. Instead, we propose another antifungal mechanism based on MRJP/yellow proteins in the defensive exudates. PMID:27068683

  8. Biological activities of recombinant equine luteinizing hormone/chorionic gonadotropin (eLH/CG) expressed in Sf9 and Mimic insect cell lines.

    Science.gov (United States)

    Legardinier, Sébastien; Duonor-Cérutti, Martine; Devauchelle, Gérard; Combarnous, Yves; Cahoreau, Claire

    2005-02-01

    Equine luteinizing hormone (eLH) and chorionic gonadotropin (eCG) are composed of identical alpha and beta polypeptide chains, but eCG subunits are much more heavily glycosylated and sialylated. Consequently, eCG exhibits a much longer half-life than eLH in blood. Recombinant eLH/CG, expressed in Sf9 and Mimic insect cells, were compared with one another and to the natural hormones eCG and eLH. Mimic cells are stably-transformed Sf9 cells, expressing five mammalian genes encoding glycosyltransferases involved in the synthesis of complex N-carbohydrate chains. Recombinant eLH/CG expressed in Mimic cells exhibited a higher apparent molecular weight (MW) than that expressed in Sf9 cells, suggesting that its N-glycosylation was, as expected, more complete. Nevertheless, the two recombinant eLH/CG exhibited lower MW than natural eCG from pregnant mare plasma. The two eLH/CG produced in Sf9 and Mimic cells were found to be active in in vitro LH and FSH bioassays, with potencies similar to those of eCG. By contrast, they exhibited no significant in vivo bioactivity, neither in the specific follicle-stimulating hormone (FSH) assay nor in the specific eCG assay. Although recombinant eLH/CG produced in Mimic cells bears more elaborate carbohydrate chains than recombinant eLH/CG from Sf9 cells, it exhibits no significant in vivo bioactivity, probably because of insufficient terminal sialylation of its carbohydrate chains, leading to its rapid removal from blood.

  9. Synthesis and evaluation of cardiac glycoside mimics as potential anticancer drugs

    DEFF Research Database (Denmark)

    Jensen, Marie; Schmidt, Steffen; Fedosova, Natalya

    2011-01-01

    The cardiac glycoside digitoxin, consisting of a steroid core linked to a labile trisaccharide, has been used for centuries for the treatment of congestive heart failure. The well known pharmacological effect is a result of the ability of cardiac glycosides to inhibit the Na(+), K(+)-ATPase. With...

  10. Aminocyclopentanols as sugar mimics. Synthesis from unsaturated bicyclic lactones by Overman rearrangement

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Fanefjord, Mette; Lundt, Inge

    2007-01-01

    Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta-D-N-acetylglucosaminid......Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta...

  11. Design and synthesis of discontinuous protein binding site mimics of HIV gp120

    NARCIS (Netherlands)

    Mulder, G.E.

    2013-01-01

    Essentially all cellular processes are mediated by protein-protein interactions and detailed knowledge about these interactions can aid in determining biological functions or provide opportunities for the treatment of human disease. Extensive research has been performed on the development of

  12. Synthesis and interactions of sulfated C5a-receptor and CHIPS mimics

    NARCIS (Netherlands)

    Bunschoten, A.|info:eu-repo/dai/nl/304836958

    2010-01-01

    Post-translational modifications are modifications of peptides or proteins after they have been synthesized in the ribosomes. These post-translational modifications (PTM’s) are intended to augment functional diversity of the 20 natural L-amino acids of which proteins are constructed. PTM’s have impo

  13. Inhibition of duck hepatitis B virus replication by mimic peptides in vitro

    Science.gov (United States)

    JIA, HONGYU; LIU, CHANGHONG; YANG, YING; ZHU, HAIHONG; CHEN, FENG; LIU, JIHONG; ZHOU, LINFU

    2015-01-01

    The aim of the present study was to investigate the inhibitory effect of specific mimic peptides targeting duck hepatitis B virus polymerase (DHBVP) on duck hepatitis B virus (DHBV) replication in primary duck hepatocytes. Phage display technology (PDT) was used to screen for mimic peptides specifically targeting DHBVP and the associated coding sequences were determined using DNA sequencing. The selected mimic peptides were then used to treat primary duck hepatocytes infected with DHBV in vitro. Infected hepatocytes expressing the mimic peptides intracellularly were also prepared. The cells were divided into mimic peptide groups (EXP groups), an entecavir-treated group (positive control) and a negative control group. The medium was changed every 48 h. Following a 10-day incubation, the cell supernatants were collected. DHBV-DNA in the cellular nucleus, cytoplasm and culture supernatant was analyzed by quantitative polymerase chain reaction (qPCR). Eight mimic peptides were selected following three PDT screening rounds for investigation in the DHBV-infected primary duck hepatocytes. The qPCR results showed that following direct treatment with mimic peptide 2 or 7, intracellular expression of mimic peptide 2 or 7, or treatment with entecavir, the DHBV-DNA levels in the culture supernatant and cytoplasm of duck hepatocytes were significantly lower than those in the negative control (P<0.05). The cytoplasmic DHBV-DNA content of the cells treated with mimic peptide 7 was lower than that in the other groups (P<0.05). In addition, the DHBV-DNA content of the nuclear fractions following the intracellular expression of mimic peptide 7 was significantly lower than that in the other groups (P<0.05). Mimic peptides specifically targeting DHBVP, administered directly or expressed intracellularly, can significantly inhibit DHBV replication in vitro. PMID:26640539

  14. Superoxide dismutases, lung function and bronchial responsiveness in a general population

    NARCIS (Netherlands)

    Siedlinski, M.; van Diemen, C. C.; Postma, D. S.; Vonk, J. M.; Boezen, H. M.

    2009-01-01

    Oxidative stress is an important causative factor in the onset and progression of smoking-related lung diseases, such as chronic obstructive pulmonary disease (COPD). Superoxide dismutases (SODs) can prevent an increase in oxidative burden. A total of 1,390 subjects from the prospective Viagtwedde-V

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

    Science.gov (United States)

    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 ...

  16. Superoxide dismutase activity in mesocarp tissue from divergent Cucumis melo L. genotypes

    Science.gov (United States)

    Muskmelon (Cucumis melo L.) fruit matrix is unique among plant foods in being able to provide a protective medium in which the antioxidant activity of the enzyme superoxide dismutase (SOD) is preserved during the digestive process, and therefore, being able to elicit in vivo pharmacological effects ...

  17. Murine Extracellular Superoxide Dismutase Is Converted into the Inactive Fold by the Ser195Cys Mutation

    DEFF Research Database (Denmark)

    Scavenius, Carsten; Petersen, Jane Savskov; Thomsen, Line Rold

    2013-01-01

    We have previously shown that human extracellular superoxide dismutase (EC-SOD) exists as two variants with differences in their disulfide bridge patterns: one form is the active enzyme (aEC-SOD), and the other is inactive (iEC-SOD). The availability of both active and inactive folding variants...

  18. Superoxide Dismutase Protects Cells from DNA Damage Induced by Trivalent Methylated Arsenicals

    Science.gov (United States)

    Superoxide dismutase (SOD) catalyzes the conversion of superoxide to hydrogen peroxide. Heterozygous mice of strain B6; 129S7-Sod1(tm1Leb)/J were obtained from Jackson Laboratories and bred to produce offspring that were heterozygous (+/Sod1(tm1Leb)), homozygous wild-type (+/+), ...

  19. Inclusions of amyotrophic lateral sclerosis-linked superoxide dismutase in ventral horns, liver, and kidney

    DEFF Research Database (Denmark)

    Jonsson, P.A.; Bergemalm, D.; Andersen, P.M.

    2008-01-01

    Mutant superoxide dismutases type 1 (SOD1s) cause amyotrophic lateral sclerosis by an unidentified toxic property. In a patient carrying the G127X truncation mutation, minute amounts of SOD1 were found in ventral horns using a mutant-specific antibody. Still, both absolute levels and ratios versus...

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

    Science.gov (United States)

    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....

  1. Identification of two peanut germin-like genes and the potential superoxide dismutase activity

    Science.gov (United States)

    Germin and germin-like protein (GLP) genes are members of large multigene families. These genes have been reported to play a role directly or indirectly in plant defense response. A number of GLPs have been demonstrated to have superoxidase dismutase (SOD) or oxalate oxidase (OxO) activity, leading ...

  2. Exogenous superoxide dismutase may lose its antidotal ability on rice leaves

    Science.gov (United States)

    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...

  3. Superoxide Dismutase 3 Polymorphism Associated with Reduced Lung Function in Two Large Populations

    DEFF Research Database (Denmark)

    Dahl, Morten; Bowler, Russell P; Juul, Klaus

    2008-01-01

    Rationale: Superoxide dismutase (SOD) 3 inhibits oxidative fragmentation of lung matrix components Collagen 1, hyaluronan, and heparan sulfate. Inherited change in SOD3 expression or function could affect lung matrix homeostasis and influence pulmonary function. Objectives: To identify novel SOD3...

  4. Low activity of superoxide dismutase and high activity of glutathione reductase in erythrocytes from centenarians

    DEFF Research Database (Denmark)

    Andersen, Helle Raun; Jeune, B; Nybo, H

    1998-01-01

    aged between 60 and 79 years. MEASUREMENTS: enzyme activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase, catalase and glutathione reductase (GR) in erythrocytes. Functional capacity among the centenarians was evaluated by Katz' index of activities of daily living, the Physical...

  5. Copper-Zinc Superoxide Dismutase: A Unique Biological "Ligand" for Bioinorganic Studies.

    Science.gov (United States)

    Valentine, Joan Selverstone; de Freitas, Duarte Mota

    1985-01-01

    Discusses superoxide dismutase (SOD) research and the properties of copper, zinc (Cu, Zn)-SOD. Emphasizes the controversy concerning the role of Cu,Zn-SOD and other SOD enzymes as protective agents in reactions involving dioxygen metabolism, and the properties of Cu, Zn-SOD that make it an interesting biological ligand for physical studies of…

  6. Do Superoxide Dismutase (SOD) and Catalase (CAT) protect Cells from DNA Damage Induced by Active Arsenicals?

    Science.gov (United States)

    Superoxide dismutase (SOD) catalyzes the conversion of superoxide to hydrogen peroxide, which can be converted to water and oxygen through the action of catalase. Heterozygous mice of strain B6: 129S7-SodltmlLeb/J were obtained from Jackson Laboratories and bred to produce offspr...

  7. Induction of peroxidases and superoxide dismutases in transformed embryogenic calli of alfalfa (Medicago sativa L.)

    Science.gov (United States)

    Activities of peroxidase (POD) and superoxide dismutase (SOD) enzymes were analyzed in non-regenerative transformed embryogenic lines of alfalfa (Medicago sativa L.) carrying wound-inducible oryzacystatin I (OC-I), wound-inducible oryzacystatin I antisense (OC-Ias) or hygromycin phosphotransferase (...

  8. A new formula to calculate activity of superoxide dismutase in indirect assays

    NARCIS (Netherlands)

    Zhang, Chen; Bruins, Marieke E.; Yang, Zhi Qiang; Liu, Shu Tao; Rao, Ping Fan

    2016-01-01

    To calculate superoxide dismutase (SOD) activity rapidly and accurately by indirect SOD assays, a formula based on the ratio of the catalytic speed of SOD to the reaction speed of the indicator with superoxide anion was deduced. The accuracy of this formula was compared with the conventional form

  9. Cu,Zn Superoxide Dismutase Maturation and Activity Are Regulated by COMMD1

    NARCIS (Netherlands)

    Vonk, Willianne I. M.; Wijmenga, Cisca; Berger, Ruud; van de Sluis, Bart; Klomp, Leo W. J.

    2010-01-01

    The maturation and activation of the anti-oxidant Cu, Zn superoxide dismutase (SOD1) are highly regulated processes that require several post-translational modifications. The maturation of SOD1 is initiated by incorporation of zinc and copper ions followed by disulfide oxidation leading to the forma

  10. Lecithinized copper,zinc-superoxide dismutase as a protector against doxorubicin-induced cardiotoxicity in mice.

    NARCIS (Netherlands)

    Hartog, den GJ; Haenen, GR; Boven, E.; Vijgh, van der WJ

    2004-01-01

    Production of superoxide radicals from doxorubicin is widely accepted to be the cause of the cardiotoxicity induced by this antitumor agent. Pretreatment with superoxide dismutase could improve the therapeutic application. Aim of the present study was to determine whether lecithinized superoxide

  11. A comparison of quantitative and qualitative superoxide dismutase assays for application to low temperature microalgae

    NARCIS (Netherlands)

    Janknegt, P.J.; Rijstenbil, J.W.; van de Poll, W.H.; Gechev, T.S.; Buma, A.G.J.

    2007-01-01

    Antioxidant enzymes such as superoxide dismutase (SOD) play a key role in the removal of reactive oxygen species produced during visible and ultraviolet irradiance stress in microalgae and plants. However, little is known about the enzymatic antioxidative stress responses in ecologically important A

  12. A comparison of quantitative and qualitative superoxide dismutase assays for application to low temperature microalgae

    NARCIS (Netherlands)

    Janknegt, P.J.; Rijstenbil, J.W.; van de Poll, W.H.; Gechev, T.S.; Buma, A.G.J.

    2007-01-01

    Antioxidant enzymes such as superoxide dismutase (SOD) play a key role in the removal of reactive oxygen species produced during visible and ultraviolet irradiance stress in microalgae and plants. However, little is known about the enzymatic antioxidative stress responses in ecologically important

  13. The concentration of extracellular superoxide dismutase in plasma is maintained by LRP-mediated endocytosis

    DEFF Research Database (Denmark)

    Petersen, Steen V; Thøgersen, Ida B; Valnickova, Zuzana;

    2010-01-01

    In this study, we show that human extracellular superoxide dismutase (EC-SOD) binds to low-density lipoprotein receptor-related protein (LRP). This interaction is most likely responsible for the removal of EC-SOD from the blood circulation via LRP expressed in liver tissue. The receptor recogniti...

  14. Copper complexes of 1,10-phenanthroline and related compounds as superoxide dismutase mimetics.

    Science.gov (United States)

    Bijloo, G J; van der Goot, H; Bast, A; Timmerman, H

    1990-11-01

    In a preliminary study we tested CuSO4.5H2O, (Cu(II]2[3,5-diisopropylsalicylate]4.2H2O and a number of copper complexes of substituted 1,10-phenanthrolines for superoxide anion dismutase activity. It appeared that this activity depends on the ligands involved and might be governed by the redox potential of the Cu(I) complex/Cu(II) complex couple. The strong superoxide anion dismutase activity of Cu(II)[DMP]2 complex can be expected considering its high redox potential. Rather surprisingly is the superoxide anion dismutase activity of the Cu(I)[DMP]2 complex since it involves oxidation to Cu(II)[DMP]2 complex. From regression analysis it was established that steric and field effects of the substituents of the investigated phenanthrolines play an important role in SOD activity and therefore it is concluded that complex formation is important for the superoxide dismutase-like activity.

  15. Stress Response in Lactococcus lactis : Cloning, Expression Analysis, and Mutation of the Lactococcal Superoxide Dismutase Gene

    NARCIS (Netherlands)

    Sanders, Jan Willem; Leenhouts, Kees J.; Haandrikman, Alfred J.; Venema, Gerard; Kok, Jan

    In an analysis of the stress response of Lactococcus lactis, three proteins that were induced under low pH culture conditions were detected. One of these was identified as the lactococcal superoxide dismutase (SodA) by N-terminal amino acid sequence analysis. The gene encoding this protein,

  16. Molecular Cloning and Expression of Sequence Variants of Manganese Superoxide Dismutase Genes from Wheat

    Science.gov (United States)

    Reactive oxygen species (ROS) are very harmful to living organisms due to the potential oxidation of membrane lipids, DNA, proteins, and carbohydrates. Transformed E.coli strain QC 871, superoxide dismutase (SOD) double-mutant, with three sequence variant MnSOD1, MnSOD2, and MnSOD3 manganese supero...

  17. Batesian mimics influence the evolution of conspicuousness in an aposematic salamander.

    Science.gov (United States)

    Kraemer, A C; Serb, J M; Adams, D C

    2015-05-01

    Conspicuousness, or having high contrast relative to the surrounding background, is a common feature of unpalatable species. Several hypotheses have been proposed to explain the occurrence of conspicuousness, and while most involve the role of conspicuousness as a direct signal of unpalatability to potential predators, one hypothesis suggests that exaggerated conspicuousness may evolve in unpalatable species to reduce predator confusion with palatable species (potential Batesian mimics). This hypothesis of antagonistic coevolution between palatable and unpalatable species hinges on the 'cost of conspicuousness', in which conspicuousness increases the likelihood of predation more in palatable species than in unpalatable species. Under this mimicry scenario, four patterns are expected: (i) mimics will more closely resemble local models than models from other localities, (ii) there will be a positive relationship between mimic and model conspicuousness, (iii) models will be more conspicuous in the presence of mimics, and (iv) when models and mimics differ in conspicuousness, mimics will be less conspicuous than models. We tested these predictions in the salamander mimicry system involving Notophthalmus viridescens (model) and one colour morph of Plethodon cinereus (mimic). All predictions were supported, indicating that selection for Batesian mimicry not only influences the evolution of mimics, but also the evolution of the models they resemble. These findings indicate that mimicry plays a large role in the evolution of model warning signals, particularly influencing the evolution of conspicuousness. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  18. [Denervation of mimic muscles during endoscopic lifting of the upper part of face].

    Science.gov (United States)

    Pinchuk, V D; Tkach, O S

    2013-08-01

    Endoscopic lifting of the upper part of face carry out in 28 patients Chemical or surgical denervation had been done for decreasing of mimic muscles activity. Medical glue with folic acid had been used for tissues fixation. Use of medical glue in conjunction with preliminary chemical denervation of mimic muscles with botulin toxin application decreases surgery duration, prevents complications and increases satisfaction of patients.

  19. Double-stranded Let-7 mimics, potential candidates for cancer gene therapy.

    Science.gov (United States)

    Wang, Qi-zhao; Lv, Ying-hui; Gong, Yu-hua; Li, Zhao-fa; Xu, William; Diao, Yong; Xu, Ruian

    2012-03-01

    MicroRNAs (miRNAs), a class of small, single-stranded endogenous RNAs, act as post-transcriptional regulators of gene expression. The ability of one single miRNA regulating multiple functionally related mRNAs makes it a new potential candidate for cancer gene therapy. Let-7s miRNAs have been demonstrated as tumor-suppressor genes in various types of cancers, providing one choice of gene therapy by replenishing this miRNA. In the present studies, we demonstrate that the chemically synthesized, double-stranded Let-7 mimics can inhibit the growth and migration and induce the cell cycle arrest of lung cancer cell lines in vitro. Let-7 mimics silence gene expression by binding to the 3' UTR of targeting mRNAs. Mutation of seed sequence significantly depresses the gene silencing activity of Let-7 mimics. Our results also demonstrate that it is possible to increase the activity of Let-7s through mutating the sequence within the 3'end of the antisense strand. Directly, co-transfection Let-7 mimics with active siRNAs impairs the anti-cancer activities of Let-7 mimics. However, a 3-h interval between the introduction of Let-7 mimics and a kind of siRNA avoids the competition and enhances the anti-cancer activities of Let-7 mimics. Taken together, these results have revealed that Let-7s mimics are potential candidates for cancer gene therapy.

  20. Effect of rice fat mimics on texture and microstructure of low-fat yoghurt

    Institute of Scientific and Technical Information of China (English)

    XU Dan; KONG Baohua; LIU Huaiwei

    2007-01-01

    This paper made a research on a new kind of rice fat mimics, which was obtained from rice powder hydrolyzed by a -amylase. Through the comparison between the yoghurt added with diverse proportions of above mentioned rice fat mimics and the reduced-fat yoghurt without any fat mimics as well as full-fat ones, the effect of the rice fat mimics in different proportions was examined upon the composition, the microstructure, the texture and the sensory evaluation of reduced-fat yoghurt. The results showed that the yoghurts added with rice fat mimics exhibited similar organoleptic attribute, textual characteristics and acceptability compared to those of full-fat controls(P>0.05), but with lower fat content and looser microstructures.

  1. Functional and crystallographic characterization of Salmonella typhimurium Cu,Zn superoxide dismutase coded by the sodCI virulence gene

    NARCIS (Netherlands)

    Pesce, A; Battistoni, A; Stroppolo, ME; Polizio, F; Nardini, M; Kroll, JS; Langford, PR; O'Neill, P; Sette, M; Desideri, A; Bolognesi, M

    2000-01-01

    The functional and three-dimensional structural features of Cu,Zn superoxide dismutase coded by the Salmonella typhimurium sodCI gene, have been characterized. Measurements of the catalytic rate indicate that this enzyme is the most efficient superoxide dismutase analyzed so far, a feature that may

  2. Stroke mimics under the drip-and-ship paradigm.

    Science.gov (United States)

    Mehta, Sonal; Vora, Nirav; Edgell, Randall C; Allam, Hesham; Alawi, Aws; Koehne, Jennifer; Kumar, Abhay; Feen, Eliahu; Cruz-Flores, Salvador; Alshekhlee, Amer

    2014-01-01

    Recent reports suggested better outcomes associated with the drip-and-ship paradigm for acute ischemic stroke (AIS) treated with thrombolysis. We hypothesized that a higher rate of stroke mimics (SM) among AIS treated in nonspecialized stroke centers that are transferred to comprehensive centers is responsible for such outcomes. Consecutive patients treated with thrombolysis according to the admission criteria were reviewed in a single comprehensive stroke center over 1 academic year (July 1, 2011 to June 30, 2012). Information on the basic demographic, hospital complications, psychiatric diagnoses, and discharge disposition was collected. We identified those patients who were treated at a facility and then transferred to the tertiary center (ie, drip-and-ship paradigm). In addition to comparative and adjusted analysis to identify predictors for SM, a stratified analysis by the drip-and-ship status was performed. One hundred twenty patients were treated with thrombolysis for AIS included in this analysis; 20 (16.7%) were discharged with the final diagnosis of SM; 14 of those had conversion syndrome and 6 patients had other syndromes (seizures, migraine, and hypoglycemia). Patients with SM were younger (55.6 ± 15.0 versus 69.4 ± 14.9, P = .0003) and more likely to harbor psychiatric diagnoses (45% versus 9%; P ≤ .0001). Eighteen of 20 SM patients (90%) had the drip-and-ship treatment paradigm compared with 65% of those with AIS (P = .02). None of the SM had hemorrhagic complications, and all were discharged to home. Predictors of SM on adjusted analysis included the drip-and-ship paradigm (odds ratio [OR] 12.8, 95% confidence interval [CI] 1.78, 92.1) and history of any psychiatric illness (OR 12.08; 95% CI 3.14, 46.4). Eighteen of 83 drip-and-ship patients (21.7%) were diagnosed with SM compared with 2 of 37 patients (5.4%) presented directly to the hub hospital (P = .02). The drip-and-ship paradigm and any psychiatric history predict the diagnosis of

  3. Metalloprotein mimics - old tools in a new light.

    Science.gov (United States)

    Happe, Thomas; Hemschemeier, Anja

    2014-04-01

    Metalloproteins utilize metal cofactors to catalyze essential reactions in all organisms. They carry out thermodynamically challenging substrate conversions such as the oxidation of water or hydrocarbons, the reduction of nitrogen to ammonium, and generation of molecular hydrogen. Besides their fundamental role in nature, metalloenzymes have promising biotechnological applications that aim to generate high-value chemicals, drugs, nutrients, biofuels, or electricity. Recent reports that a chemically synthesized compound is able to reconstitute [2Fe]-hydrogenases, harboring an especially elaborate and highly efficient metal cofactor, promise to pave the way for gaining much deeper insight into the function of even complex metal enzymes. What is more, synthetic biology approaches such as the chemical synthesis of artificial hydrogenases seem to be in reach.

  4. Manganese superoxide dismutase, but not CuZn superoxide dismutase, is highly expressed in the granulomas of pulmonary sarcoidosis and extrinsic allergic alveolitis.

    Science.gov (United States)

    Lakari, E; Pääkkö, P; Kinnula, V L

    1998-08-01

    The role of antioxidant defense mechanisms in the pathogenesis of granulomatous human lung diseases remains open to investigation. In this study we investigated the immunoreactivity of two important superoxide radical scavenging intracellular antioxidant enzymes, manganese superoxide dismutase (MnSOD) and copperzinc superoxide dismutase (CuZnSOD), in pulmonary sarcoidosis and extrinsic allergic alveolitis. In histologically normal lung MnSOD was variable but mostly positive in the cells of bronchial epithelium, alveolar epithelium especially in type II pneumocytes, and alveolar macrophages. Copperzinc SOD showed positive immunoreactivity most markedly in the bronchial epithelium. The biopsies of 22 patients with pulmonary sarcoidosis and 10 with extrinsic allergic alveolitis indicated that MnSOD was highly stained in the granulomas of both diseases, with 60 to 100% of the granulomas showing intensive immunoreactivity. Western blots conducted on the cell samples of bronchoalveolar lavage (BAL) fluid revealed significantly higher amounts of MnSOD in sarcoidosis and extrinsic allergic alveolitis than in the controls. Immunohistochemistry on the cells obtained from BAL fluid showed positive immunoreactivity of MnSOD in the macrophages but not in the lymphocytes. In contrast, copperzinc SOD was not induced in either of these diseases. We conclude that MnSOD is highly expressed in the granulomas of pulmonary sarcoidosis and extrinsic allergic alveolitis, and variable but mostly positive in alveolar macrophages, possibly owing to cytokine mediated induction during the granuloma formation.

  5. A novel route for preparing 5' cap mimics and capped RNAs: phosphate-modified cap analogues obtained via click chemistry.

    Science.gov (United States)

    Walczak, Sylwia; Nowicka, Anna; Kubacka, Dorota; Fac, Kaja; Wanat, Przemyslaw; Mroczek, Seweryn; Kowalska, Joanna; Jemielity, Jacek

    2017-01-01

    The significant biological role of the mRNA 5' cap in translation initiation makes it an interesting subject for chemical modifications aimed at producing useful tools for the selective modulation of intercellular processes and development of novel therapeutic interventions. However, traditional approaches to the chemical synthesis of cap analogues are time-consuming and labour-intensive, which impedes the development of novel compounds and their applications. Here, we explore a different approach for synthesizing 5' cap mimics, making use of click chemistry (CuAAC) to combine two mononucleotide units and yield a novel class of dinucleotide cap analogues containing a triazole ring within the oligophosphate chain. As a result, we synthesized a library of 36 mRNA cap analogues differing in the location of the triazole ring, the polyphosphate chain length, and the type of linkers joining the phosphate and the triazole moieties. After biochemical evaluation, we identified two analogues that, when incorporated into mRNA, produced transcripts translated with efficiency similar to compounds unmodified in the oligophosphate bridge obtained by traditional synthesis. Moreover, we demonstrated that the triazole-modified cap structures can be generated at the RNA 5' end using two alternative capping strategies: either the typical co-transcriptional approach, or a new post-transcriptional approach based on CuAAC. Our findings open new possibilities for developing chemically modified mRNAs for research and therapeutic applications, including RNA-based vaccinations.

  6. Characterization and mapping of a novel light-dependent lesion mimic mutant Imm6 in rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    XIAO Gui-qing[1,2; ZHANG Hal-wen[3; LU Xiang-yang[1,2; HUANG Rong-feng[3

    2015-01-01

    A novel rice lesion mimic mutant (LMM) was isolated from an ethane methyl sulfonate (EMS)-induced 02428 mutant bank. The mutant, tentatively designated as Imm6, develops necrotic lesions in the whole growth period along with changes in several important agronomic traits. We found that the initiation of the lesions was induced by light and cell death occurred in Imm6 accompanied with accumulation of reactive oxygen species (ROS). The lower chlorophyll content, soluble protein content and superoxide dismutase (SOD) activity, the higher malondialdehyde (MDA) content were detected in Imm6 than in the wild type (WT). Moreover, the observation by transmission electronic microscope (TEM) demonstrated that some organelles were damaged and the stroma lamella of chloroplast was irregular and loose in mesophyll cell of Imm6. In addition, Imm6 was more resistant than WT to rice blast fungus Magnaporthe grisea infection, which was consistent with increased expression of four genes involved in the defense-related reaction. Genetic analysis showed that mutant trait of Imm6 is inherited as a monogenic recessive nuclear gene located on the long arm of chromosome 6. Using simple sequence repeat (SSR) markers, the target gene was finally delimited to an interval of 80.8 kb between markers MM2359 and MM2370, containing 7 annotated genes. Taken together, our results provide the information to identify a new gene involved in rice lesion mimic, which will be helpful in clarifying the mechanism of cell death and disease resistance in rice.

  7. Extracellular superoxide dismutase is present in secretory vesicles of human neutrophils and released upon stimulation

    DEFF Research Database (Denmark)

    Iversen, Marie B; Gottfredsen, Randi H; Larsen, Ulrike G

    2016-01-01

    Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme present in the extracellular matrix (ECM), where it provides protection against oxidative degradation of matrix constituents including type I collagen and hyaluronan. The enzyme is known to associate with macrophages and polymor......Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme present in the extracellular matrix (ECM), where it provides protection against oxidative degradation of matrix constituents including type I collagen and hyaluronan. The enzyme is known to associate with macrophages......), the protein was released into the extracellular space and found to associate with DNA released from stimulated cells. The functional consequences were evaluated by the use of neutrophils isolated from wild-type and EC-SOD KO mice, and showed that EC-SOD release significantly reduce the level of superoxide...

  8. Cryo-Trapping the Distorted Octahedral Reaction Intermediate of Manganese Superoxide Dismutase

    Science.gov (United States)

    Borgstahl, Gloria; Snell, Edward H.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    Superoxide dismutase protects organisms from potentially damaging oxygen radicals by catalyzing the disproportion of superoxide to oxygen and hydrogen peroxide. We report the use of cryogenic temperatures to kinetically trap the 6th ligand bound to the active site of manganese superoxide dismutase. Using cryocrystallography and synchrotron radiation, we describe at 1.55A resolution the six-coordinate, distorted octahedral geometry assumed by the active site during catalysis and compare it to the room temperature, five-coordinate trigonal-bipyramidal active site. Gateway residues Tyr34, His30 and a tightly bound water molecule are implicated in closing off the active site and blocking the escape route of superoxide during dismutation.

  9. Superoxide Dismutase 1 Loss Disturbs Intracellular Redox Signaling, Resulting in Global Age-Related Pathological Changes

    Directory of Open Access Journals (Sweden)

    Kenji Watanabe

    2014-01-01

    Full Text Available Aging is characterized by increased oxidative stress, chronic inflammation, and organ dysfunction, which occur in a progressive and irreversible manner. Superoxide dismutase (SOD serves as a major antioxidant and neutralizes superoxide radicals throughout the body. In vivo studies have demonstrated that copper/zinc superoxide dismutase-deficient (Sod1−/− mice show various aging-like pathologies, accompanied by augmentation of oxidative damage in organs. We found that antioxidant treatment significantly attenuated the age-related tissue changes and oxidative damage-associated p53 upregulation in Sod1−/− mice. This review will focus on various age-related pathologies caused by the loss of Sod1 and will discuss the molecular mechanisms underlying the pathogenesis in Sod1−/− mice.

  10. Superoxide dismutase from Trichuris ovis, inhibiton by benzimidazoles and pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    M. Sanchez-Moreno

    1992-01-01

    Full Text Available Three superoxide dismutase isoenzymes of different cellular location were detected in an homogenate of Thrichuris 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 intensitive Mn-Sod were higher than that of the superoxide dismutase detected in the cytoplasmic fraction (cyanid sensitive Cu-Zn-SOD. All the mollecular forms present evident differences to the SODs contained in the host liver. Molecular mass and some of the physical and chemical aproperties 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 wich markedly inhibited parasite ensyme but not host enzyme.

  11. SUPEROXIDE DISMUTASE ACTIVITY AND MEMBRANE LIPIDSCOMPOSITION OF ERYTHROCYTES IN PATIENTS WITH DILATEDCARDIOMYOPATHY

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To further confirm the role of lipid-peroxidation caused by oxygen free radicals injury played in the pathogenesis of dilsted cardiomypathy. Methods The superoxide dismutase activities and lipids composi tion of erythrocytes in 18 patients with dilated cardiomyopathy and 16 healthy controls were measured. Results ① Su peroxide dismutase(SOD) activites of erythrocytes were lower in dilated cardiomyopathy(DCM) patients than that in healthy controls (P <0. 001). ②The lipids composition of erythrocytes has changed in the DCM patients compared with healthy controls: total lipids changed little (P>0. 05); total phospholipids were lower, but not significantly (P >0.05); total cholesterol increased significantly (P <0. 05). The cholesterol to phospholipids molecular ratio of erythrocyte membrane has increased remarkably (P>0. 05). Conclusion It can be supposed that decreased SOD ac tivities play an important role in the damage of membrane system and the pathogensis of DCM.

  12. The effects of superoxide dismutase knockout on the oxidative stress parameters and survival of mouse erythrocytes.

    Science.gov (United States)

    Grzelak, Agnieszka; Kruszewski, Marcin; Macierzyńska, Ewa; Piotrowski, Łukasz; Pułaski, Łukasz; Rychlik, Błazej; Bartosz, Grzegorz

    2009-01-01

    The erythrocytes of 12-month old Sod1 (-/-) mice showed an increased level of reactive oxygen species (ROS), as estimated by the degree of dihydroethidine and dihydrorhodamine oxidation, and the increased level of Heinz bodies. No indices of severe oxidative stress were found in the red blood cells and blood plasma of Sod1 (-/-) mice as judged from the lack of significant changes in the levels of erythrocyte and plasma glutathione, plasma protein thiol and carbonyl groups and thiobarbituric-acid reactive substances in the blood plasma. However, a decreased erythrocyte lifespan, increased reticulocyte count and splenomegaly were noted, indicating the importance of superoxide dismutase for maintaining erythrocyte viability. The levels of erythrocyte ROS and Heinz bodies and the reticulocyte count were indistinguishable in Sod1 (+/+) and Sod1 (+/-) mice, suggesting that a superoxide dismutase activity decrease to half of its normal value may be sufficient to secure the protective effects of the enzyme.

  13. High-throughput synthesis of stable isotope-labeled transmembrane proteins for targeted transmembrane proteomics using a wheat germ cell-free protein synthesis system.

    Science.gov (United States)

    Takemori, Nobuaki; Takemori, Ayako; Matsuoka, Kazuhiro; Morishita, Ryo; Matsushita, Natsuki; Aoshima, Masato; Takeda, Hiroyuki; Sawasaki, Tatsuya; Endo, Yaeta; Higashiyama, Shigeki

    2015-02-01

    Using a wheat germ cell-free protein synthesis system, we developed a high-throughput method for the synthesis of stable isotope-labeled full-length transmembrane proteins as proteoliposomes to mimic the in vivo environment, and we successfully constructed an internal standard library for targeted transmembrane proteomics by using mass spectrometry.

  14. Glial nuclear aggregates of superoxide dismutase-1 are regularly present in patients with amyotrophic lateral sclerosis

    OpenAIRE

    2011-01-01

    The most common cause of amyotrophic lateral sclerosis (ALS) is mutations in superoxide dismutase-1 (SOD1). Since there is evidence for the involvement of non-neuronal cells in ALS, we searched for signs of SOD1 abnormalities focusing on glia. Spinal cords from nine ALS patients carrying SOD1 mutations, 51 patients with sporadic or familial ALS who lacked such mutations, and 46 controls were examined by immunohistochemistry. A set of anti-peptide antibodies with specificity for misfolded SOD1...

  15. Low autophagy capacity implicated in motor system vulnerability to mutant superoxide dismutase

    OpenAIRE

    2016-01-01

    Introduction The motor system is selectively vulnerable to mutations in the ubiquitously expressed aggregation-prone enzyme superoxide dismutase-1 (SOD1). Results Autophagy clears aggregates, and factors involved in the process were analyzed in multiple areas of the CNS from human control subjects (n = 10) and amyotrophic lateral sclerosis (ALS) patients (n = 18) with or without SOD1 mutations. In control subjects, the key regulatory protein Beclin 1 and downstream factors were remarkably sca...

  16. REGENERASI DAN PERBANYAKAN RUMPUT LAUT Kappaphycus alvarezii HASIL TRANSFORMASI GEN SUPEROKSIDA DISMUTASE (MaSOD)

    OpenAIRE

    Emma Suryati; Hidayah Triana; Utut Widiastuti; Andi Tenriulo

    2017-01-01

    Transformasi gen superoxide dismutase (MaSOD) pada rumput laut Kappaphycus alvarezii menggunakan Agrobacterium tumefacient telah dilakukan secara in vitro. Transformasi gen MaSOD ke dalam genom rumput laut diharapkan dapat mengurangi cekaman oksidatif terutama yang disebabkan oleh perubahan suhu, salinitas, dan cemaran logam di perairan. Penelitian ini bertujuan untuk regenerasi rumput laut hasil introduksi gen MaSOD dan non-transgenik pada labu kultur. Regenerasi dan perbanyakan rumput laut ...

  17. Perbandingan Optimasi Biosensor Antioksidan Menggunakan Ekstrak dan Enzim Murni Superoksida Dismutase

    Directory of Open Access Journals (Sweden)

    Imas Eva Wijayanti

    2016-01-01

    Full Text Available Abstract: An antioxidant biosensor has been developed for measurement of antioxidant capacity. The purpose of this study was to determine and compare the activity of the superoxide dismutase (SOD enzyme from the crude extract of Deinococcus radiodurans cells and pure SOD from bovine erythrocytes which were immobilized on zeolite nanoparticles (ZNP. The kinetics parameters were also determined. The optimum condition was obtained by Response Surface Method. The immobilized crude extract D. radiodurans SOD (CES modified carbon paste electrode (CPE (CES-ZNP-CPE have different optimum conditions with the modified carbon paste electrode pure SOD immobilization (PS-ZNP-CPE. This is shown by the difference in the two structures. Erythrocyte SOD enzyme from cows that have the type of Cu / Zn-SOD, whereas SOD extracted from the bacterium D. radiodurans is the type of Mn-SOD. The differences in the structure cause the Cu / Zn SOD and Mn-SOD has a different reaction mechanism, so that responses and measurement will be differences resulted.Keywords: Antioxidant biosensor, Immobilization, Superoxide dismutase, Zeolite nanoparticlesAbstrak: Biosensor antioksidan telah dikembangkan untuk pengukuran kapasitas antioksidan. Tujuan dari penelitian ini adalah untuk menentukan dan membandingkan aktivitas enzim superoksida dismutase (SOD dari ekstrak kasar sel bakteri Deinococcus radiodurans dan SOD murni dari eritrosit sapi yang diimobilisasi pada nanopartikel zeolit (ZNP. Kondisi optimum diperoleh dengan metode respon permukaan. Elektrode pasta karbon yang dimodifikasi ekstrak kasar SOD D. radiodurans imobilisasi (CES-ZNP-CPE memiliki kondisi optimum yang berbeda dengan  elektrode pasta karbon yang dimodifikasi SOD murni imobilisasi (PS-ZNP-CPE. Hal ini disebabkan karena perbedaan struktur keduanya. Enzim SOD dari eritrosit sapi yang memiliki tipe Cu/Zn-SOD, sedangkan SOD yang diekstrak dari bakteri D. radiodurans adalah tipe Mn-SOD. Perbedaan  struktur

  18. Absence of superoxide dismutase activity causes nuclear DNA fragmentation during the aging process

    Energy Technology Data Exchange (ETDEWEB)

    Muid, Khandaker Ashfaqul; Karakaya, Hüseyin Çaglar; Koc, Ahmet, E-mail: ahmetkoc@iyte.edu.tr

    2014-02-07

    Highlights: • Aging process increases ROS accumulation. • Aging process increases DNA damage levels. • Absence of SOD activity does not cause DNA damage in young cells. • Absence of SOD activity accelerate aging and increase oxidative DNA damages during the aging process. - Abstract: Superoxide dismutases (SOD) serve as an important antioxidant defense mechanism in aerobic organisms, and deletion of these genes shortens the replicative life span in the budding yeast Saccharomyces cerevisiae. Even though involvement of superoxide dismutase enzymes in ROS scavenging and the aging process has been studied extensively in different organisms, analyses of DNA damages has not been performed for replicatively old superoxide dismutase deficient cells. In this study, we investigated the roles of SOD1, SOD2 and CCS1 genes in preserving genomic integrity in replicatively old yeast cells using the single cell comet assay. We observed that extend of DNA damage was not significantly different among the young cells of wild type, sod1Δ and sod2Δ strains. However, ccs1Δ mutants showed a 60% higher amount of DNA damage in the young stage compared to that of the wild type cells. The aging process increased the DNA damage rates 3-fold in the wild type and more than 5-fold in sod1Δ, sod2Δ, and ccs1Δ mutant cells. Furthermore, ROS levels of these strains showed a similar pattern to their DNA damage contents. Thus, our results confirm that cells accumulate DNA damages during the aging process and reveal that superoxide dismutase enzymes play a substantial role in preserving the genomic integrity in this process.

  19. Molecular cloning and biochemical characterization of iron superoxide dismutase from the rodent malaria parasite Plasmodium vinckei.

    Science.gov (United States)

    Prakash, Kirtika; Goyal, Manish; Soni, Awakash; Siddiqui, Arif Jamal; Bhardwaj, Jyoti; Puri, Sunil K

    2014-12-01

    Plasmodium parasite utilizes superoxide dismutase family proteins to limit the toxicity of reactive oxygen species, such as produced through hemoglobin degradation. These proteins play an important role in parasite survival during intra-erythrocytic phase. We have identified, and biochemically characterized a putative iron dependent superoxide dismutase from rodent malaria parasite Plasmodium vinckei (PvSOD1). The recombinant PvSOD1 protein was purified to homogeneity through a combination of affinity and gel filtration chromatography. Crosslinking, Native-PAGE and FPLC gel filtration analyses documented that PvSOD1 exists as a dimer in solution, a common feature shared by other Fe-SODs. PvSOD1 is cytosolic in localization and its expression is comparatively higher during trophozoite as compared to that of ring and schizont stages. Enzymatic activity of recombinant PvSOD1 was validated using conventional zymogram analyses and xanthine-xanthine oxidase system. Under optimal conditions, PvSOD1 was highly active and catalyzed the dismutation of superoxide radicals. Furthermore, PvSOD1 showed activity over a broad range of pH and temperature. Inhibition studies suggested that PvSOD1 was inactivated by hydrogen peroxide, and peroxynitrite, but not by cyanide and azide. Since, PvSOD1 plays a central role in oxidative defense mechanism, therefore, characterization of PvSOD1 will be exploited in the screening of new superoxide dismutase inhibitors for their antimalarial activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Purification and characterization of iron-cofactored superoxide dismutase from Enteromorpha linza

    Science.gov (United States)

    Lü, Mingsheng; Cai, Ruanhong; Wang, Shujun; Liu, Zhaopu; Jiao, Yuliang; Fang, Yaowei; Zhang, Xiaoxin

    2013-11-01

    A superoxide dismutase was purified from Enteromorpha linza using a simple and safe procedure, which comprised phosphate buffer extraction, ammonium sulphate precipitation, ion exchange chromatography on Q-sepharose column, and gel filtration chromatography on Superdex 200 10/300GL. The E. linza superoxide dismutase ( ElSOD) was purified 103.6-fold, and a yield of 19.1% and a specific activity of 1 750 U/mg protein were obtained. The SDS-PAGE exhibited ElSOD a single band near 23 kDa and the gel filtration study showed ElSOD's molecular weight is near 46 kDa in nondenatured condition, indicating it's a homodimeric protein. El SOD is an iron-cofactored superoxide dismutase (Fe-SOD) because it was inhibited by hydrogen peroxide, insensitive to potassium cyanide. The optimal temperature for its maximal enzyme activity was 35°C, and it still had 29.8% relative activity at 0°C, then ElSOD can be classified as a cold-adapted enzyme. ElSOD was stable when temperature was below 40°C or the pH was within the range of 5-10. The first 11 N-terminal amino acids of ElSOD were ALELKAPPYEL, comparison of its N-terminal sequence with other Fe-SOD N-terminal sequences at the same position suggests it is possibly a chloroplastic Fe-SOD.

  1. Assessment of antioxidants status and superoxide dismutase activity in HIV-infected children

    Directory of Open Access Journals (Sweden)

    Camila Pugliese

    2014-09-01

    Full Text Available Objective: This study aims to assess the nutritional status of selenium, copper and zinc; and also the erythrocyte superoxide dismutase activity of HIV-infected children compared to a control group. Methods: A cross-sectional study was carried out with prepubertal HIV-infected children (n = 51 and their healthy siblings (n = 32. All biochemical measurements including plasma selenium, serum copper levels, serum and erythrocyte zinc levels and erythrocyte super-oxide dismutase activity were evaluated according to dietary, clinical and biochemical parameters. Results: Compared to the control group, the HIV-infected children had lower z-score values for height-for-age (p = 0.0006, higher prevalence of stunting (11.8% (p = 0.047, lower selenium levels (p = 0.0006 and higher copper levels (p = 0.019. No difference was found concerning superoxide dismutase activity (p > 0.05. The HIV-infected group presented a higher proportion (45.1% of children with zinc intakes below the estimated average requirement (p = 0.014; however, no association with zinc biochemical parameters was found. Conclusion: HIV-infected children have an inadequate selenium and copper nutritional status, which could influence the progression to AIDS. An adequate micronutrient status could improve the clinical conditions in these patients and minimize free radical production and cellular oxidative stress.

  2. Structure of glycosylated Cu/Zn-superoxide dismutase from Kluyveromyces yeast NBIMCC 1984

    Science.gov (United States)

    Dolashka-Angelova, Pavlina; Moshtanska, Vesela; Kujumdzieva, Anna; Atanasov, Boris; Petrova, Vencislava; Voelter, Wolfgang; Beeumen, Jozef Van

    2010-09-01

    The primary structure of Cu/Zn-superoxide dismutase from Kluyveromyces marxianus NBIMCC 1984 was elucidated by N-terminal sequence analysis of the intact protein and by determination of the amino acid sequences of tryptic peptides by MALDI-TOF-TOF tandem mass spectrometry. The molecular mass of one subunit of the homodimer SOD, containing 152 amino acid residues, was calculated to be 15858.3 Da while a value of 17096.63 Da was obtained by MALDI-TOF MS. This difference is explained by the presence of N-glycosylation of one linkage site, -Asn-Ile/Leu-Thr-, and a glycan chain with the structure Hex 5 GlcNAc 2. Glycosylation of K.marxianus superoxide dismutase is a post-translational modification. Recent developments in mass spectrometry have enabled detailed structural analyses of covalent modifications of proteins. Therefore, in this paper, we introduce a covalent modification of Cu/Zn-SOD from K. marxianus NBIMCC 1984, by analysis of the enzymatic liberated N-glycan from the enzyme using MALDI-TOF and tandem mass spectrometry on a Q-Trap mass spectrometer. This is the first report of the structure of the oligosaccharide of a naturally-glycosylated superoxide dismutase, determined by mass spectrometry.

  3. Transformation optics that mimics the system outside a Schwarzschild black hole

    OpenAIRE

    Chen, Huanyang; Miao, Rong-Xin; Li, Miao

    2009-01-01

    We applied the transformation optics to mimic a black hole of Schwarzschild form. Similar properties of photon sphere were also found numerically for the metamaterial black hole. Several reduced versions of the black hole systems were proposed for easier implementations.

  4. Assembly of a Library of Trisaccharides as Mimics of Sialyl Lewis X via Random Combination Strategy

    Institute of Scientific and Technical Information of China (English)

    Xiang Bao MENG; Hui LI; Qing LI; Tie Ming CHENG; Zhong Jun LI

    2004-01-01

    A small library containing six positional isomers of fucosyl on the modified lactoside backbone as mimics of the Sialyl Lewis X was synthesized via random combinatorial glycosylation,which was charactered by ESI-MS and HPLC.

  5. Selective chromo-fluorogenic detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) with a unique probe based on a boron dipyrromethene (BODIPY) dye.

    Science.gov (United States)

    Barba-Bon, Andrea; Costero, Ana M; Gil, Salvador; Martínez-Máñez, Ramón; Sancenón, Félix

    2014-11-21

    A novel colorimetric probe (P4) for the selective differential detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) was prepared. Probe P4 contains three reactive sites; i.e. (i) a nucleophilic phenol group able to undergo phosphorylation with nerve gases, (ii) a carbonyl group as a reactive site for cyanide; and (iii) a triisopropylsilyl (TIPS) protecting group that is known to react with fluoride. The reaction of P4 with DCNP in acetonitrile resulted in both the phosphorylation of the phenoxy group and the release of cyanide, which was able to react with the carbonyl group of P4 to produce a colour modulation from pink to orange. In contrast, phosphorylation of P4 with DFP in acetonitrile released fluoride that hydrolysed the TIPS group in P4 to yield a colour change from pink to blue. Probe P4 was able to discriminate between DFP and DCNP with remarkable sensitivity; limits of detection of 0.36 and 0.40 ppm for DCNP and DFP, respectively, were calculated. Besides, no interference from other organophosphorous derivatives or with presence of acid was observed. The sensing behaviour of P4 was also retained when incorporated into silica gel plates or onto polyethylene oxide membranes, which allowed the development of simple test strips for the colorimetric detection of DCNP and DFP in the vapour phase. P4 is the first probe capable of colorimetrically differentiating between a Tabun mimic (DCNP) and a Sarin and Soman mimic (DFP).

  6. Cloning of a putative extracellular Cu/Zn superoxide dismutase and functional differences of superoxide dismutases in invasive and indigenous whiteflies.

    Science.gov (United States)

    Gao, Xian-Long; Li, Jun-Min; Xu, Hong-Xing; Yan, Gen-Hong; Jiu, Min; Liu, Shu-Sheng; Wang, Xiao-Wei

    2015-02-01

    Superoxide dismutases (SODs) are a group of important antioxidant defense enzymes. In this study, a putative extracellular Cu/Zn superoxide dismutase (ecCuZnSOD) complementary DNA was cloned and characterized from the whitefly, Bemisia tabaci. Quantitative polymerase chain reaction analysis showed that the expression level of BtecCuZnSOD was more than 10-fold higher in the invasive Middle East Asia Minor 1 (MEAM1) than in the native Asia II 3 species of the B. tabaci species complex. After exposure to low temperature (4 °C), the expression of Bt-ecCuZnSOD gene was significantly up-regulated in MEAM1 but not in Asia II 3. Furthermore, the expression level of B. tabaci intracellular CuZnSOD (Bt-icCuZnSOD), Bt-ecCuZnSOD and mitochondrial MnSOD (Bt-mMnSOD) was compared after transferring MEAM1 and Asia II 3 whiteflies from favorable (cotton) to unfavorable host plants (tobacco). On cotton, both CuZnSOD genes were expressed at a higher level in MEAM1 compared with Asia II 3. Interestingly, after transferring onto tobacco, the expression of Bt-ecCuZnSOD was significantly induced in Asia II 3 but not in MEAM1. On the other hand, while Bt-mMnSOD was expressed equally in both species on cotton, Bt-mMnSOD messenger RNA was up-regulated in MEAM1 on tobacco. Consistently, enzymatic activity assays of CuZnSOD and MnSOD demonstrated that CuZnSOD might play an important protective role against oxidative stress in Asia II 3, whereas MnSOD activation was critical for MEAM1 whiteflies during host adaptation. Taken together, our results suggest that the successful invasion of MEAM1 is correlated with its constitutive high activity of CuZnSOD and inducible expression of MnSOD under stress conditions.

  7. INFLUENCE OF MIMIC CARDIAC RATE ON HYDRODYNAMICS OF DIFFERENT MECHANICAL PROSTHETIC CARDIAC VALVES IN VITRO

    Institute of Scientific and Technical Information of China (English)

    Yin-ping Chu; Jin-lian Cheng; Ru-kun Chen; Yu-bo Fan; Fang Pu

    2005-01-01

    Objective To assess the influence of mimic cardiac rate on hydrodynamics of different mechanical prosthetic cardiac valves.Methods US-made CarboMedics bileaflet valve, China-made Jiuling bileaflet valve and C-L tilting disc valve were tested via a pulsatile flow simulator in the aortic position. Testing conditions were set at mimic cardiac rates of 55 bpm, 75 bpm, 100bpm with a constant mimic cardiac output of 4 L/min. The mean pressure differences (△P), leakage volumes (LEV) and closing volumes (CLV) across each valve, and effective orifice areas (EOA) were analyzed.Results Within physiological range, △p, LEV, and CLV decreased as mimic cardiac rate increased, with a large extent of variance. EOA increased along with an increase in mimic cardiac rate. It was a different response in terms of cardiac rate alteration for different types of mechanical prosthetic cardiac valves.Conclusion Mimic cardiac rate change affects hydrodynamics of mechanical prosthetic cardiac valves. Within physiological range, the hydrodynamic of prosthetic bileaflet valve is better than that of tilting disc valve.

  8. Biomarkers of Antioxidant Status, Inflammation, and Cartilage Metabolism Are Affected by Acute Intense Exercise but Not Superoxide Dismutase Supplementation in Horses

    Directory of Open Access Journals (Sweden)

    Emily D. Lamprecht

    2012-01-01

    Full Text Available Objectives were to evaluate effects of (1 repetitive arthrocentesis on biomarkers of inflammation (prostaglandin E2, PGE2 and aggrecan synthesis (chondroitin sulfate-846; CS in synovial fluid (SF; (2 exercise and superoxide dismutase (SOD supplementation on biomarkers of inflammation, antioxidant status, and aggrecan synthesis, in horses. Preliminary trial. Standardbreds underwent four arthrocentesis procedures within 48 h and exhibited elevated CS and no changes in PGE2. Exercise trial. this randomized crossover design used twelve Standardbred mares which received either treatment (3000 IU d−1 oral SOD powder or placebo (cellulose powder for 6 wks which culminated with them running a repeated sprint exercise test (RSET. Samples were collected before (PRE, during (PEAK, and following exercise (POST. Exercise resulted in increased (<0.05 antioxidant defenses including erythrocyte SOD, total glutathione, glutathione peroxidase, gene transcripts for interferon-gamma, interleukin-10, and interleukin-1β in blood, and decreased plasma nitric oxide. Exercise increased (<0.05 SF CS and adjusted-PGE2, and higher (<0.05 CS and PGE2 were found in hock versus carpus joints. No treatment effects were detected. Results suggest normal adaptive responses likely due to exercise-induced tissue microdamage and oxidative stress. Additional research is needed to identify benefit(s of SOD supplementation in horses.

  9. A novel form of the human manganese superoxide dismutase protects rat and human livers undergoing ischaemia and reperfusion injury

    National Research Council Canada - National Science Library

    Hide, Diana; Ortega-Ribera, Martí; Fernández-Iglesias, Anabel; Fondevila, Constantino; Salvadó, M Josepa; Arola, Lluís; García-Pagán, Juan Carlos; Mancini, Aldo; Bosch, Jaime; Gracia-Sancho, Jordi

    2014-01-01

    ...), liver grafts from healthy and steatotic rats, and human liver samples, we aimed to characterize the effects of a new recombinant form of human manganese superoxide dismutase (rMnSOD) on hepatic CS+WR injury. After CS...

  10. Functional Activities and Immunohistochemical Distribution of Superoxide Dismutase in Normal, Dysplastic and Squamous Cell Carcinoma Oral Tissues

    Science.gov (United States)

    2001-07-26

    Support Flight, Tyndall AFB, FL 1998 - present ......................... Orthodontic Residency, The Ohio State University FIELDS OF STUDY Major Field...Taniguchi N. Manganese superoxide dismutase expression correlates with p53 status and local recurrence of cervical carcinoma treated with radiation therapy

  11. Cloning, Expression, Characterization, and Computational Approach for Cross-Reactivity Prediction of Manganese Superoxide Dismutase Allergen from Pistachio Nut

    Directory of Open Access Journals (Sweden)

    Reihaneh Noorbakhsh

    2010-01-01

    Conclusions: For the first time recombinant manganese superoxide dismutase from nut source was expressed as a possible allergen. This pistachio allergen could be a possible basis for cross-reactivity with MnSOD from other sources.

  12. Profiling of antioxidant superoxide dismutase in saliva of oral submucous fibrosis patients to categorize its diagnosis in varying stages

    National Research Council Canada - National Science Library

    Yuthicka Sirohi; Devi Charan Shetty; Aadithya B Urs; Harish Chandra Rai

    2011-01-01

    ... by spectrophotometric method using assay kit (Bio Vision Catalog # K335-100). The oral submucous fibrosis cases were grouped into clinical stages and histopathological grades and superoxide dismutase ...

  13. 113Cd-NMR investigation of a cadmium-substituted copper, zinc-containing superoxide dismutase from yeast

    DEFF Research Database (Denmark)

    Kofod, Pauli; Bauer, Rogert; Danielsen, Eva

    1991-01-01

    113Cd nuclear magnetic resonance spectroscopy has been used to investigate the metal binding sites of cadmium-substituted copper,zinc-containing superoxide dismutase from baker's yeast. NMR signals were obtained for 113Cd(II) at the Cu site as well as for 113Cd(II) at the Zn site. The two subunits...... an explanation for the discrepancy in the literature regarding 113Cd-NMR investigations of bovine superoxide dismutase....

  14. Iron, copper, and manganese complexes with in vitro superoxide dismutase and/or catalase activities that keep Saccharomyces cerevisiae cells alive under severe oxidative stress.

    Science.gov (United States)

    Ribeiro, Thales P; Fernandes, Christiane; Melo, Karen V; Ferreira, Sarah S; Lessa, Josane A; Franco, Roberto W A; Schenk, Gerhard; Pereira, Marcos D; Horn, Adolfo

    2015-03-01

    Due to their aerobic lifestyle, eukaryotic organisms have evolved different strategies to overcome oxidative stress. The recruitment of some specific metalloenzymes such as superoxide dismutases (SODs) and catalases (CATs) is of great importance for eliminating harmful reactive oxygen species (hydrogen peroxide and superoxide anion). Using the ligand HPClNOL {1-[bis(pyridin-2-ylmethyl)amino]-3-chloropropan-2-ol}, we have synthesized three coordination compounds containing iron(III), copper(II), and manganese(II) ions, which are also present in the active site of the above-noted metalloenzymes. These compounds were evaluated as SOD and CAT mimetics. The manganese and iron compounds showed both SOD and CAT activities, while copper showed only SOD activity. The copper and manganese in vitro SOD activities are very similar (IC50~0.4 μmol dm(-3)) and about 70-fold higher than those of iron. The manganese compound showed CAT activity higher than that of the iron species. Analyzing their capacity to protect Saccharomyces cerevisiae cells against oxidative stress (H2O2 and the O2(•-) radical), we observed that all compounds act as antioxidants, increasing the resistance of yeast cells mainly due to a reduction of lipid oxidation. Especially for the iron compound, the data indicate complete protection when wild-type cells were exposed to H2O2 or O2(•-) species. Interestingly, these compounds also compensate for both superoxide dismutase and catalase deficiencies; their antioxidant activity is metal ion dependent, in the order iron(III)>copper(II)>manganese(II). The protection mechanism employed by the complexes proved to be independent of the activation of transcription factors (such as Yap1, Hsf1, Msn2/Msn4) and protein synthesis. There is no direct relation between the in vitro and the in vivo antioxidant activities. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. CNS bioavailability and radiation protection of normal hippocampal neurogenesis by a lipophilic Mn porphyrin-based superoxide dismutase mimic, MnTnBuOE-2-PyP5+

    Directory of Open Access Journals (Sweden)

    David Leu

    2017-08-01

    Full Text Available Although radiation therapy can be effective against cancer, potential damage to normal tissues limits the amount that can be safely administered. In central nervous system (CNS, radiation damage to normal tissues is presented, in part, as suppressed hippocampal neurogenesis and impaired cognitive functions. Mn porphyrin (MnP-based redox active drugs have demonstrated differential effects on cancer and normal tissues in experimental animals that lead to protection of normal tissues and radio- and chemo-sensitization of cancers. To test the efficacy of MnPs in CNS radioprotection, we first examined the tissue levels of three different MnPs – MnTE-2-PyP5+(MnE, MnTnHex-2-PyP5+(MnHex, and MnTnBuOE-2-PyP5+(MnBuOE. Nanomolar concentrations of MnHex and MnBuOE were detected in various brain regions after daily subcutaneous administration, and MnBuOE was well tolerated at a daily dose of 3 mg/kg. Administration of MnBuOE for one week before cranial irradiation and continued for one week afterwards supported production and long-term survival of newborn neurons in the hippocampal dentate gyrus. MnP-driven S-glutathionylation in cortex and hippocampus showed differential responses to MnP administration and radiation in these two brain regions. A better understanding of how preserved hippocampal neurogenesis correlates with cognitive functions following cranial irradiation will be helpful in designing better MnP-based radioprotection strategies.

  16. Superoxide dismutase activity in mesocarp tissue from divergent Cucumis melo L. genotypes.

    Science.gov (United States)

    Lester, Gene E; Jifon, John L; Crosby, Kevin M

    2009-09-01

    Muskmelons (Cucumis melo L.) are well-known as excellent sources of several vitamins, minerals and non-enzymatic antioxidant phytochemicals such as vitamin C and pro-vitamin A. Less well-studied is their potential role as sources of enzymatic antioxidants such as superoxide dismutase (SOD), which have been associated with enhanced reactive oxygen species scavenging capacity in some muskmelon fruits. In this study, we investigated the variability in SOD activities among diverse advanced breeding lines and commercial muskmelon cultivars grown in two different soil types-clay or sandy loam. Specific and total SOD activities varied significantly among the genotypes (P melo as a functional food with enhanced SOD content.

  17. A Novel Isoenzyme of CuZn-superoxide Dismutase from Nicotiana tobacum

    Institute of Scientific and Technical Information of China (English)

    Liang Quan SHENG; Shao Min LIU; Hou Rong XIAO; Bing Le XIA; Qing Liang LIU

    2004-01-01

    An isoenzyme of CuZn-superoxide dismutase, denoted as CuZnSODⅢ, has been separated and purified from Nicotiana Tobacum (tobacco) leaves to apparent homogeneity. Its molecular mass is 22976.6Da. It is composed of one subunit, which is consisted of 187 amine acid residues and contains 1 copper and 0.5 zinc atom. The activation energy of the thermal denaturation process has been obtained as about 143.5kJmol-1. Meanwhile, some properties of spectra were investigated.

  18. Interaction of Copper in CuZn-Superoxide Dismutase With Histidine

    Institute of Scientific and Technical Information of China (English)

    胡皆汉; 舒占永

    1994-01-01

    The interaction of CuZn-superoxide dismutase ( CuZn-SOD ) with the external histidine in aqueous solution has been studied in this work by ESR and NMR. It is found that the Cu(Ⅱ) of CuZn-SOD makes an exchanging interaction with the external substance in aqueous solution. Unlike in solid state, the Cu(Ⅱ) forms complex with external histidine, and keeps a motional equilibrium between the active centers and the complexes. Enzyme activity is also affected by this interaction. Some other amino acids are also discussed in this paper.

  19. A new formula to calculate activity of superoxide dismutase in indirect assays.

    Science.gov (United States)

    Zhang, Chen; Bruins, Marieke E; Yang, Zhi-Qiang; Liu, Shu-Tao; Rao, Ping-Fan

    2016-06-15

    To calculate superoxide dismutase (SOD) activity rapidly and accurately by indirect SOD assays, a formula based on the ratio of the catalytic speed of SOD to the reaction speed of the indicator with superoxide anion was deduced. The accuracy of this formula was compared with the conventional formula based on inhibition in five indirect SOD assays. The new formula was validated in nearly the entire SOD activity range, whereas the conventional formula was validated only during inhibition of 40-60%. This formula might also be used for the assays of other enzymes.

  20. GAMMA RADIATION EFFECT ON SUPEROXIDE DISMUTASE ACTIVITY IN HYPERICUM PERFORATUM L. AND ECHINACEA PURPUREA L., MOENCH

    Directory of Open Access Journals (Sweden)

    Vlad Artenie

    2006-08-01

    Full Text Available In this paper we were focused on the activity of superoxide dismutase (SOD in Hypericum perforatum L and Echinacea purpurea L., Moench plantlets, obtained from seeds irradiated with gamma rays before germination.Total activity as well as specific activity of SOD in Hypericum perforatum L. plantlets shows an inhibition, which becames higher at higher irradiation doses. For Echinacea purpurea L. species, gamma radiation shows a slowly stimulative effect of total activity of SOD for some of the higher doses, but the specific enzyme activity is inhibated for all irradiation doses applyed on non-germinated irradiated seeds.

  1. Levels of Lipid Perioxides and Superoxide Dismutase in Peritoneal Fluid of Patients with Endometriosis

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to evaluate the changes of lipid perioxides (LPO) and superoxide dismutase (SOD) levels in peritoneal fluid in patients with endometriosis, the levels of LPO and SOD in peritoneal fluids from infertile women with endometriosis and with normal pelvis were measured. The result showed that the levels of LPO but SOD was elevated significantly in peritoneal fluid from women with endometriosis than in women with normal pelvis (P<0.01). It is suggested that free oxygen radicals may be involved in the pathogenesis of endometriosis associated infertility.

  2. Production of superoxide and activity of superoxide dismutase in rabbit epididymal spermatozoa.

    Science.gov (United States)

    Holland, M K; Alvarez, J G; Storey, B T

    1982-12-01

    Mature rabbit spermatozoa from the cauda epididymidis suspended in potassium Tris phosphate buffer at 24 degrees C produced O2.-, as measured by reduction of acetylated ferricytochrome c, with an intrinsic rate of 0.20 nmol/min per 10(8) cells. This rate increased to 1.80 nmol/min per 10(8) cells in the presence of 10 mM cyanide. These spermatozoa contain 2.8 units per 10(8) cells of superoxide dismutase activity, 95% of which is sensitive, and 5% of which is insensitive, to cyanide inhibition. These activities correspond to the cytosolic Cu-Zn form and the mitochondrial Mn form of the dismutase, respectively. Only the cyanide-sensitive form is released from the sperm on hypo-osmotic treatment or sonication. Hypo-osmotically treated rabbit epididymal spermatozoa produced O2.- with an intrinsic rate of 0.24 nmol/min per 10(8) cells, which increased to 0.58 nmol/min per 10(8) cells in the presence of 10 mM cyanide. Both intact and hypo-osmotically treated cells react with O2.- in a second order reaction as inferred from the hyperbolic dependence on cell concentration of O2.- production rate in both the absence and presence of cyanide. The second order rate constant for this reaction with intact cells, kS, was calculated to be 22.9 X 10(-8) (cells/ml)-1 min-1 in its absence. For hypo-osmotically treated cells, the values of kS were 10.8 X 10(-8) (cells/ml)-1 min-1 and 8.2 X 10(-8) (cells/ml) -1 min-1, respectively. Since hypo-osmotically treated cells have lost much of their plasma membrane, the lower value of kS for the treated cells implies that this membrane is one site of reaction of O2.- with the cells. The increase in kS in the presence of cyanide, which inhibits superoxide dismutase and so increases O2.- production, suggests that the cells become more reactive with O2.- as its production rate increase, as would be expected for the occurrence of radical chain oxidation. This in turn suggests that superoxide dismutase plays a major role in protecting rabbit sperm

  3. Modeling and analysis of soybean (Glycine max. L Cu/Zn, Mn and Fe superoxide dismutases

    Directory of Open Access Journals (Sweden)

    V. Ramana Gopavajhula

    2013-01-01

    Full Text Available Superoxide dismutase (SOD, EC 1.15.1.1 is an important metal-containing antioxidant enzyme that provides the first line of defense against toxic superoxide radicals by catalyzing their dismutation to oxygen and hydrogen peroxide. SOD is classified into four metalloprotein isoforms, namely, Cu/Zn SOD, Mn SOD, Ni SOD and Fe SOD. The structural models of soybean SOD isoforms have not yet been solved. In this study, we describe structural models for soybean Cu/Zn SOD, Mn SOD and Fe SOD and provide insights into the molecular function of this metal-binding enzyme in improving tolerance to oxidative stress in plants.

  4. Synthesis and Optical Resolution of 2-Aryl-2-fluoropropionic Acids, Fluorinated Analogues of Non-steroidal Anti-inflammatory Drugs (NSAIDs)

    National Research Council Canada - National Science Library

    Fujisawa, Hidehito; Fujiwara, Tomoya; Takeuchi, Yoshio; Omata, Kenji

    2005-01-01

    We report the synthesis of optically active 2-aryl-2-fluoropropionic acids 2 as non-epimerizable mimics of 2-arylpropionic acids 1, a class of compounds which have been widely used as non-steroidal...

  5. Antimicrobial Effects of Novel Triple Antibiotic Paste–Mimic Scaffolds on Actinomyces naeslundii Biofilm

    Science.gov (United States)

    Albuquerque, Maria T.P.; Ryan, Stuart J.; Münchow, Eliseu A.; Kamocka, Maria M.; Gregory, Richard L.; Valera, Marcia C.; Bottino, Marco C.

    2015-01-01

    Introduction Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)–mimic scaffold is proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm. Methods Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm3, n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability. Results Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly (P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant (P regenerative endodontics. PMID:25917945

  6. A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing.

    Science.gov (United States)

    Ismail, Anisa S; Valastyan, Julie S; Bassler, Bonnie L

    2016-04-13

    Host-microbial symbioses are vital to health; nonetheless, little is known about the role crosskingdom signaling plays in these relationships. In a process called quorum sensing, bacteria communicate with one another using extracellular signal molecules called autoinducers. One autoinducer, AI-2, is proposed to promote interspecies bacterial communication, including in the mammalian gut. We show that mammalian epithelia produce an AI-2 mimic activity in response to bacteria or tight-junction disruption. This AI-2 mimic is detected by the bacterial AI-2 receptor, LuxP/LsrB, and can activate quorum-sensing-controlled gene expression, including in the enteric pathogen Salmonella typhimurium. AI-2 mimic activity is induced when epithelia are directly or indirectly exposed to bacteria, suggesting that a secreted bacterial component(s) stimulates its production. Mutagenesis revealed genes required for bacteria to both detect and stimulate production of the AI-2 mimic. These findings uncover a potential role for the mammalian AI-2 mimic in fostering crosskingdom signaling and host-bacterial symbioses.

  7. Phenotype of transgenic mice carrying a very low copy number of the mutant human G93A superoxide dismutase-1 gene associated with amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Jeffrey S Deitch

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disease of the motor neuron. While most cases of ALS are sporadic, 10% are familial (FALS with 20% of FALS caused by a mutation in the gene that codes for the enzyme Cu/Zn superoxide dismutase (SOD1. There is variability in sporadic ALS as well as FALS where even within the same family some siblings with the same mutation do not manifest disease. A transgenic (Tg mouse model of FALS containing 25 copies of the mutant human SOD1 gene demonstrates motor neuron pathology and progressive weakness similar to ALS patients, leading to death at approximately 130 days. The onset of symptoms and survival of these transgenic mice are directly related to the number of copies of the mutant gene. We report the phenotype of a very low expressing (VLE G93A SOD1 Tg carrying only 4 copies of the mutant G93ASOD1 gene. While weakness can start at 9 months, only 74% of mice 18 months or older demonstrate disease. The VLE mice show decreased motor neurons compared to wild-type mice as well as increased cytoplasmic translocation of TDP-43. In contrast to the standard G93A SOD1 Tg mouse which always develops motor weakness leading to death, not all VLE animals manifested clinical disease or shortened life span. In fact, approximately 20% of mice older than 24 months had no motor symptoms and only 18% of VLE mice older than 22 months reached end stage. Given the variable penetrance of clinical phenotype, prolonged survival, and protracted loss of motor neurons the VLE mouse provides a new tool that closely mimics human ALS. This tool will allow the study of pathologic events over time as well as the study of genetic and environmental modifiers that may not be causative, but can exacerbate or accelerate motor neuron disease.

  8. Conformational Plasticity in Glycomimetics: Fluorocarbamethyl-L-idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings.

    Science.gov (United States)

    Unione, Luca; Xu, Bixue; Díaz, Dolores; Martín-Santamaría, Sonsoles; Poveda, Ana; Sardinha, João; Rauter, Amelia Pilar; Blériot, Yves; Zhang, Yongmin; Cañada, F Javier; Sollogoub, Matthieu; Jiménez-Barbero, Jesus

    2015-07-13

    Sugar function, structure and dynamics are intricately correlated. Ring flexibility is intrinsically related to biological activity; actually plasticity in L-iduronic rings modulates their interactions with biological receptors. However, the access to the experimental values of the energy barriers and free-energy difference for conformer interconversion in water solution has been elusive. Here, a new generation of fluorine-containing glycomimetics is presented. We have applied a combination of organic synthesis, NMR spectroscopy and computational methods to investigate the conformational behaviour of idose- and glucose-like rings. We have used low-temperature NMR spectroscopic experiments to slow down the conformational exchange of the idose-like rings. Under these conditions, the exchange rate becomes slow in the (19) F NMR spectroscopic chemical shift timescale and allows shedding light on the thermodynamic and kinetic features of the equilibrium. Despite the minimal structural differences between these compounds, a remarkable difference in their dynamic behaviour indeed occurs. The importance of introducing fluorine atoms in these sugars mimics is also highlighted. Only the use of (19) F NMR spectroscopic experiments has permitted the unveiling of key features of the conformational equilibrium that would have otherwise remained unobserved.

  9. Towards Structural-Functional Mimics of Acetylene Hydratase: Reversible Activation of Acetylene using a Biomimetic Tungsten Complex.

    Science.gov (United States)

    Peschel, Lydia M; Belaj, Ferdinand; Mösch-Zanetti, Nadia C

    2015-10-26

    The synthesis and characterization of a biomimetic system that can reversibly bind acetylene (ethyne) is reported. The system has been designed to mimic catalytic intermediates of the tungstoenzyme acetylene hydratase. The thiophenyloxazoline ligand S-Phoz (2-(4',4'-dimethyloxazolin-2'-yl)thiophenolate) is used to generate a bioinspired donor environment around the W center, facilitating the stabilization of W-acetylene adducts. The featured complexes [W(C2 H2 )(CO)(S-Phoz)2 ] (2) and [WO(C2 H2 )(S-Phoz)2 ] (3) are extremely rare from a synthetic and structural point of view as very little is known about W-C2 H2 adducts. Upon exposure to visible light, 3 can release C2 H2 from its coordination sphere to yield the 14-electron species [WO(S-Phoz)2 ] (4). Under light-exclusion 4 re-activates C2 H2 making this the first fully characterized system for the reversible activation of acetylene.

  10. Estimating the size of non-observed economy in Croatia using the MIMIC approach

    Directory of Open Access Journals (Sweden)

    Vjekoslav Klarić

    2011-03-01

    Full Text Available This paper gives a quick overview of the approaches that have been used in the research of shadow economy, starting with the definitions of the terms “shadow economy” and “non-observed economy”, with the accent on the ISTAT/Eurostat framework. Several methods for estimating the size of the shadow economy and the non-observed economy are then presented. The emphasis is placed on the MIMIC approach, one of the methods used to estimate the size of the nonobserved economy. After a glance at the theory behind it, the MIMIC model is then applied to the Croatian economy. Considering the described characteristics of different methods, a previous estimate of the size of the non-observed economy in Croatia is chosen to provide benchmark values for the MIMIC model. Using those, the estimates of the size of non-observed economy in Croatia during the period 1998-2009 are obtained.

  11. Catalytic hyperbranched polymers as enzyme mimics; exploiting the principles of encapsulation and supramolecular chemistry.

    Science.gov (United States)

    Kirkorian, Katerina; Ellis, Adam; Twyman, Lance J

    2012-09-21

    Nature uses the principles of encapsulation and supramolecular chemistry to bind and orientate substrates within active catalytic sites. Over the years, synthetic chemistry has generated a number of small molecule active site mimics capable of catalysing reactions involving bound substrates. Another approach uses larger molecules that better represent an enzymes globular structure. These molecules mimic an enzymes structure by incorporating binding/catalytic sites within the globular structure of the polymer. As such, the electronic and steric properties around the binding/catalytic site(s) can be controlled and fine-tuned. One class of polymer that is particularly adept at mimicking the globular structure of enzymes are dendritic polymers. This review will concentrate on the use of hyperbranched polymers as synthetic enzyme mimics.

  12. Cloning, Purification, and Characterization of Recombinant Human Extracellular Superoxide Dismutase in SF9 Insect Cells.

    Science.gov (United States)

    Shrestha, Pravesh; Yun, Ji-Hye; Kim, Woo Taek; Kim, Tae-Yoon; Lee, Weontae

    2016-03-01

    A balance between production and degradation of reactive oxygen species (ROS) is critical for maintaining cellular homeostasis. Increased levels of ROS during oxidative stress are associated with disease conditions. Antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD), in the extracellular matrix (ECM) neutralize the toxicity of superoxide. Recent studies have emphasized the importance of EC-SOD in protecting the brain, lungs, and other tissues from oxidative stress. Therefore, EC-SOD would be an excellent therapeutic drug for treatment of diseases caused by oxidative stress. We cloned both the full length (residues 1-240) and truncated (residues 19-240) forms of human EC-SOD (hEC-SOD) into the donor plasmid pFastBacHTb. After transposition, the bacmid was transfected into the Sf9-baculovirus expression system and the expressed hEC-SOD purified using FLAG-tag. Western blot analysis revealed that hEC-SOD is present both as a monomer (33 kDa) and a dimer (66 kDa), as detected by the FLAG antibody. A water-soluble tetrazolium (WST-1) assay showed that both full length and truncated hEC-SOD proteins were enzymatically active. We showed that a potent superoxide dismutase inhibitor, diethyldithiocarbamate (DDC), inhibits hEC-SOD activity.

  13. Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett's esophagus

    Institute of Scientific and Technical Information of China (English)

    Elena Piazuelo; Carmelo Cebrián; Alfredo Escartín; Pilar Jiménez; Fernando Soteras; Javier Ortego; Angel Lanas

    2005-01-01

    AIM: To test whether antioxidant treatment could prevent the progression of Barrett's esophagus to adenocarcinoma.METHODS: In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric preservation, groups of 6-10 rats were randomized to receive treatment with superoxide dismutase (SOD) or vehicle and followed up for 4 mo. Rat's esophagus was assessed by histological analysis, superoxide anion and peroxinitrite generation, SOD levels and DNA oxidative damage.RESULTS: All rats undergoing esophagojejunostomy developed extensive esophageal mucosal ulceration and inflammation by mo 4. The process was associated with a progressive presence of intestinal metaplasia beyondthe anastomotic area (9% 1st mo and 50% 4th mo) (94% at the anastomotic level) and adenocarcinoma(11% 1st mo and 60% 4th mo). These changes were associated with superoxide anion and peroxinitrite mucosal generation, an early and significant increase of DNA oxidative damage and a significant decrease in SOD levels (P<0.05). Exogenous administration of SOD decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the risk of developing intestinal metaplasia beyond the anastomotic area (odds ratio = 0.326; 95%CI: 0.108-0.981; P = 0.046),and esophageal adenocarcinoma (odds ratio = 0.243;95%CI: 0.073-0.804; P = 0.021).CONCLUSION: Superoxide dismutase prevents the progression of esophagitis to Barrett's esophagus and adenocarcinoma in this rat model of gastrointestinal reflux, supporting a role of antioxidants in the chemoprevention of esophageal adenocarcinoma.

  14. Recombinant Mitochondrial Manganese Containing Superoxide Dismutase Protects Against Ochratoxin A-Induced Nephrotoxicity.

    Science.gov (United States)

    Ciarcia, Roberto; Damiano, Sara; Squillacioti, Caterina; Mirabella, Nicola; Pagnini, Ugo; Florio, Alessia; Severino, Lorella; Capasso, Giovambattista; Borrelli, Antonella; Mancini, Aldo; Boffo, Silvia; Romano, Gaetano; Giordano, Antonio; Florio, Salvatore

    2016-06-01

    Ochratoxin A (OTA) is a natural mycotoxin, involved in the development of important human and animal diseases. In this work we have studied the role of oxidative stress in the development of OTA nephrotoxicity and the effect of a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) to prevent kidney damage induced by OTA. Blood pressure, glomerular filtration rate and renal histology were analyzed in control rats and in OTA treated rats. In addition, lipid peroxidation, catalase and superoxide dismutase productions were measured. Our data showed that animals treated with OTA presented hypertension and reduction of glomerular filtration rate (GFR). These effects are most probably related to an increase in the reactive oxygen species (ROS) productions. In fact, we have shown that treatment with rMnSOD restored the levels of blood pressure and GFR simultaneously. Moreover, we have noted that OTA induced alteration on glomerular and tubular degeneration and interstitial infiltrates and that use of rMnSOD combined with OTA prevent this renal histological damage confirming the potential therapeutic role in the treatment of rMnSOD OTA nephrotoxicity.

  15. Structure of the manganese superoxide dismutase from Deinococcus radiodurans in two crystal forms

    Energy Technology Data Exchange (ETDEWEB)

    Dennis, Rebecca J.; Micossi, Elena; McCarthy, Joanne [Macromolecular Crystallography Group, European Synchrotron Radiation Facility, 38043 Grenoble CEDEX 9 (France); Moe, Elin [The Norwegian Structural Biology Centre, University of Tromsø, N-9037 Tromsø (Norway); Gordon, Elspeth J.; Kozielski-Stuhrmann, Sigrid; Leonard, Gordon A.; McSweeney, Sean, E-mail: mcsweeney@esrf.fr [Macromolecular Crystallography Group, European Synchrotron Radiation Facility, 38043 Grenoble CEDEX 9 (France)

    2006-04-01

    The crystal structures of two crystal forms of manganese superoxide dismutase (Mn-SOD) from the radiation-resistant bacterium D. radiodurans are reported and compared with the crystal structure of Mn-SOD from E. coli. The structure of the manganese superoxide dismutase (Mn-SOD; DR1279) from Deinococcus radiodurans has been determined in two different crystal forms. Both crystal forms are monoclinic with space group P2{sub 1}. Form I has unit-cell parameters a = 44.28, b = 83.21, c = 59.52 Å, β = 110.18° and contains a homodimer in the asymmetric unit, with structure refinement (R = 16.8%, R{sub free} = 23.6%) carried out using data to d{sub min} = 2.2 Å. Form II has unit-cell parameters a = 43.57, b = 87.10, c = 116.42 Å, β = 92.1° and an asymmetric unit containing two Mn-SOD homodimers; structure refinement was effected to a resolution of 2.0 Å (R = 17.2%, R{sub free} = 22.3%). The resulting structures are compared with that of Mn-SOD from Escherichia coli, with which they are shown to be essentially isostructural.

  16. Evolutive and structural characterization of Nostoc commune iron-superoxide dismutase that is fit for modification.

    Science.gov (United States)

    Ma, Y; Lu, M; Li, J-Y; Qin, Y; Gong, X-G

    2012-10-04

    Superoxide dismutase (SOD) has extensive clinical applications for protecting organisms from toxic oxidation. In this study, the integrated iron-superoxide dismutase gene (fe-sod) coding sequence of Nostoc commune stain CHEN was cloned from genomic DNA and compared to sods from other reported algae. These analyses of immunology and phylogenetics indicated that this Fe-SOD is considerably homologous with SODs from lower prokaryotes (Fe-SOD or Mn-SOD) but not those from higher animals (Cu/Zn-SOD). In addition, the N. commune Fe-SOD shows 67 to 93% protein sequence identity to 10 other algal Fe-SODs (or Mn-SODs) and 69 to 93% gene sequence identity. Rare nonsynonymous substitutions imply that algal SODs are being subjected to strong natural selection. Interestingly, the N. commune Fe-SOD enzyme molecule has a compact active center that is highly conserved (38.1% of residues are absolutely conserved), and 2 loose ends localized outside the molecule and inclined to mutate (only 11.5% of residues are absolutely conserved). Based on associative analyses of evolution, structure, and function, this special phenomenon is attributed to function-dependent evolution through negative natural selection. Under strong natural selection, although the mutation is random on the gene level, the exterior region is inclined to mutate on the protein level owing to more nonsynonymous substitutions in the exterior region, which demonstrates the theoretical feasibility of modifying Fe-SOD on its ends to overcome its disadvantages in clinical applications.

  17. Chlorite dismutases - a heme enzyme family for use in bioremediation and generation of molecular oxygen.

    Science.gov (United States)

    Hofbauer, Stefan; Schaffner, Irene; Furtmüller, Paul G; Obinger, Christian

    2014-04-01

    Chlorite is a serious environmental concern, as rising concentrations of this harmful anthropogenic compound have been detected in groundwater, drinking water, and soil. Chlorite dismutases (Clds) are therefore important molecules in bioremediation as Clds catalyze the degradation of chlorite to chloride and molecular oxygen. Clds are heme b-containing oxidoreductases present in numerous bacterial and archaeal phyla. This review presents the phylogeny of functional Clds and Cld-like proteins, and demonstrates the close relationship of this novel enzyme family to the recently discovered dye-decolorizing peroxidases. The available X-ray structures, biophysical and enzymatic properties, as well as a proposed reaction mechanism, are presented and critically discussed. Open questions about structure-function relationships are addressed, including the nature of the catalytically relevant redox and reaction intermediates and the mechanism of inactivation of Clds during turnover. Based on analysis of currently available data, chlorite dismutase from "Candidatus Nitrospira defluvii" is suggested as a model Cld for future application in biotechnology and bioremediation. Additionally, Clds can be used in various applications as local generators of molecular oxygen, a reactivity already exploited by microbes that must perform aerobic metabolic pathways in the absence of molecular oxygen. For biotechnologists in the field of chemical engineering and bioremediation, this review provides the biochemical and biophysical background of the Cld enzyme family as well as critically assesses Cld's technological potential.

  18. Unique Characteristics of Recombinant Hybrid Manganese Superoxide Dismutase from Staphylococcus equorum and S. saprophyticus.

    Science.gov (United States)

    Retnoningrum, Debbie S; Rahayu, Anis Puji; Mulyanti, Dina; Dita, Astrid; Valerius, Oliver; Ismaya, Wangsa T

    2016-04-01

    A recombinant hybrid of manganese dependent-superoxide dismutase of Staphylococcus equorum and S. saprophyticus has successfully been overexpressed in Escherichia coli BL21(DE3), purified, and characterized. The recombinant enzyme suffered from degradation and aggregation upon storage at -20 °C, but not at room temperature nor in cold. Chromatographic analysis in a size exclusion column suggested the occurrence of dimeric form, which has been reported to contribute in maintaining the stability of the enzyme. Effect of monovalent (Na(+), K(+)), divalent (Ca(2+), Mg(2+)), multivalent (Mn(2+/4+), Zn(2+/4+)) cations and anions (Cl(-), SO4 (2-)) to the enzyme stability or dimeric state depended on type of cation or anion, its concentration, and pH. However, tremendous effect was observed with 50 mM ZnSO4, in which thermostability of both the dimer and monomer was increased. Similar situation was not observed with MnSO4, and its presence was detrimental at 200 mM. Finally, chelating agent appeared to destabilize the dimer around neutral pH and dissociate it at basic pH. The monomer remained stable upon addition of ethylene diamine tetraacetic acid. Here we reported unique characteristics and stability of manganese dependent-superoxide dismutase from S. equorum/saprophyticus.

  19. Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets

    Science.gov (United States)

    Clinton, Tracy R; Weinstock, Matthew T; Jacobsen, Michael T; Szabo-Fresnais, Nicolas; Pandya, Maya J; Whitby, Frank G; Herbert, Andrew S; Prugar, Laura I; McKinnon, Rena; Hill, Christopher P; Welch, Brett D; Dye, John M; Eckert, Debra M; Kay, Michael S

    2015-01-01

    Ebolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti-ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N-trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad-spectrum inhibitors of ebolavirus entry. The N-trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N-trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X-ray crystallography analyses reveal the helical, trimeric structure of the designed N-trimer mimic targets. Surface plasmon resonance studies validate that the N-trimer mimic binds its native ligand, the C-peptide region of GP2. The longest N-trimer mimic also inhibits virus entry, thereby confirming binding of the C-peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N-trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N-trimer mimics as targets in mirror-image phage display, which will be used to identify d-peptide inhibitors of ebolavirus entry. PMID:25287718

  20. Perbedaan Kadar Superokside Dismutase pada Remaja dengan Dismenore Primer dan Tanpa Dismenore Primer

    Directory of Open Access Journals (Sweden)

    Yanti .

    2016-01-01

    Full Text Available Abstrak             Dismenore didefinisikan sebagai rasa kram saat menstruasi yang menyakitkan tanpa patologi yang jelas. Kram berlangsung selama satu hari atau lebih dan disertai rasa mual, diare, sakit kepala. Masalah yang ditimbulkan oleh dismenore adalah  peningkatan ketidakhadiran di sekolah pada remaja sehingga menyebabkan rendahnya nilai akademik pada pelajar. Superokside dismutase (SOD adalah bahan bioaktif yang diketahui bersifat antioksidan. SOD melindungi sel terhadap gangguan oksidan (radikal bebas. SOD mengubah anion superoksida menjadi hidrogen peroksida dan oksigen, sering disebut juga sebagai pertahanan primer terhadap stress oksidatif. Tujuan penelitian ini adalah mengetahui  perbedaan kadar superokside dismutase pada remaja dengan dismenore dan tanpa dismenore. Penelitian ini adalah observasional desain cross sectional comparative. Data dianalisis menggunakan uji Mann-Withney  dengan nilai p<0.05 dianggap bermakna secara statistik. Rerata kadar SOD pada remaja yang mengalami dismenore yaitu 36,76 u/ml dan rerata kadar SOD pada remaja tanpa dismenore yaitu 32,24 u/ml. Dengan nilai p>0,005 (0,345. Hasil penelitian ini menyimpulkan bahwa tidak terdapat perbedaan yang bermakna  kadar SOD pada remaja dengan dismenore dan tanpa dismenore. Kata kunci: remaja, dismenore, antioksidan, superokside dismutase AbstractPrimary dysmenorrhoe is  a painful menstrual cramps without obvious pathology. Cramps is lasting for one day or more, accaompanied by nausea, diarrhea and headache. Problems cause by dysmenorrhea are an increase in school attendance in adolescents resulting in low academic grades of students. Superokside Dismeutase (SOD is a bioactive ingredient that is known as antioxidants, protecting cells against harmful SOD oxidants (free radicals SOD convert superoxide anion into hydrogen perokxide and oxygen, often call  as primary defense agains oxidative stress. Primary dysmenorrhoe increased uterine activity or

  1. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks

    Science.gov (United States)

    Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

    2016-01-01

    We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

  2. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks.

    Directory of Open Access Journals (Sweden)

    Tae-Yun Kang

    Full Text Available We used indirect stereolithography (SL to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture.

  3. Inhibition of hepatitis C virus replication by single-stranded RNA structural mimics

    Institute of Scientific and Technical Information of China (English)

    Robert; Smolic; Martina; Smolic; John; H; Andorfer; Catherine; H; Wu; Robert; M; Smith; George; Y; Wu

    2010-01-01

    AIM: To examine the effect of hepatitis C virus (HCV) structural mimics of regulatory regions of the genome on HCV replication.METHODS: HCV RNA structural mimics were constructed and tested in a HCV genotype 1b aBB7 replicon,and a Japanese fulminant hepatitis-1 (JFH-1) HCV genotype 2a infection model.All sequences were computer-predicted to adopt stem-loop structures identical to the corresponding elements in full-length viral RNA.Huh7.5 cells bearing the BB7 replicon or infected with JFH-1 virus were trans...

  4. Parallel solid-phase synthesis of diaryltriazoles

    Directory of Open Access Journals (Sweden)

    Matthias Wrobel

    2012-07-01

    Full Text Available A series of substituted diaryltriazoles was prepared by a solid-phase-synthesis protocol using a modified Wang resin. The copper(I- or ruthenium(II-catalyzed 1,3-cycloaddition on the polymer bead allowed a rapid synthesis of the target compounds in a parallel fashion with in many cases good to excellent yields. Substituted diaryltriazoles resemble a molecular structure similar to established terphenyl-alpha-helix peptide mimics and have therefore the potential to act as selective inhibitors for protein–protein interactions.

  5. Teripang Pasir Meningkatkan Kandungan Antioksidan Superoksida Dismutase pada Pankreas Tikus Diabetes (SEA CUCUMBER INCREASED ANTIOXIDANT SUPEROXIDE DISMUTASE IN THE PANCREATIC TISSUE OF DIABETIC RATS

    Directory of Open Access Journals (Sweden)

    Tutik Wresdiyati

    2015-05-01

    Full Text Available High level of blood glucose is an indicator for diabetes mellitus (DM condition. The condition iscaused by low level of insulin secretion or impairement of insulin receptor. The number of DM patientincreases every year. The World Health Organization reported that the number of DM patient in Indonesiawas the 4th highest in the world, after following China, India, and the United States of America, respectively.This study was conducted to analyze the effect of sea cucumber (Holothuria scabra J on the profile ofantioxidant copper, zinc-superoxide dismutase (Cu, Zn-SOD in the pancreatic tissues of diabetic rats. Atotal of 25 male white rats (Sprague Dawley were used in this study. They were divided into five groups;(1 negative control (KN, (2 positive control, diabetic rats (KP, (3 diabetic rats treated with hydrolyzatedprotein of sea cucumber (HDL, (4 diabetic rats treated with concentrated protein of sea cucumber (KST,and (5 diabetic rats treated with isolated protein of sea cucumber (ISL, respectively. Diabetic conditionwas obtained by alloxan injection 110 mg/kg bw. The treatments were done for 28 days. At the end oftreatment period, the rats were sacrificed and pancreatic tissues were collected and fixed in Bouin solution and then processed to paraffin embedding standard method. The tissues were then stained withimmunohistochemical staining techniques using monoclonal antibody of Cu, Zn-SOD. The results showedthat treatment of HDL, KST, and ISL of sea cucumber (Holothuria scabra J increased the content ofantioxidant Cu, Zn-SOD either in Langerhans islets and acinar cells of pancreatic tissues-diabetic rats.The HDL of sea cucumber treatment gave the best effect in increasing the antioxidant content of Cu, Zn-SOD in pancreatic tissue of diabetic rats.

  6. Myocardial capillary permeability after regional ischemia and reperfusion in the in vivo canine heart. Effect of superoxide dismutase

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Bjerrum, P J; Haunsø, S

    1991-01-01

    This study assesses the effect of the superoxide anion scavenger superoxide dismutase on myocardial capillary permeability-surface area (PS) products for small hydrophilic molecules after ischemia and reperfusion. Open-chest dogs underwent a 20-minute occlusion of the left anterior descending...... the start of reperfusion. In 13 dogs, no scavenger treatment was given (nonprotected control group), whereas eight dogs were treated systemically with 15,000 units/kg superoxide dismutase during 1 hour, starting 20 minutes before ischemia. In the control group, three dogs developed reperfusion ventricular...... fibrillation in contrast to none in the superoxide dismutase group. Before ischemia, plasma flow rate, myocardial capillary extraction fraction, and PS values were similar in the two groups. Five minutes after the start of reperfusion, plasma flow rate increased significantly (p less than 0.01) in both groups...

  7. Storage of Electromagnetic Waves in a Metamaterial that Mimics Electromagnetically Induced Transparency

    CERN Document Server

    Nakanishi, Toshihiro; Tamayama, Yasuhiro; Kitano, Masao

    2013-01-01

    We propose a method for dynamically controlling the properties of a metamaterial that mimics electromagnetically induced transparency (EIT) by introducing varactor diodes to manipulate the structural symmetry of the metamaterial. Dynamic modulation of the EIT property enables the storage and retrieval of electromagnetic waves. We confirmed that the electromagnetic waves were stored and released, while maintaining the phase distribution in the propagating direction.

  8. A Molecular Mechanics Analysis of Molecular Recognition by Cyclodextrin Mimics of Alpha-Chymotrypsin

    Science.gov (United States)

    1989-05-26

    Clasification ) A Molecular Mechanics Analysis of Molecular Recognition By Cyclodextrin Mimics of Alpha-Chymotrypsin. 12. PERSONAL AUTHOR(S) C.A. Venanzil...Field Parameters The AMBER force field was developed by Kollmann and coworkers tc 28293 treat proteins and nucleic acids , as well as small molecules2 9

  9. Isolation and characterization of rice lesion mimic mutants from a T-DNA tagged population

    Institute of Scientific and Technical Information of China (English)

    LI Shutian; PEI Zhongyou; LUO Lijuan; TIAN Yingchuan; HE Chaozu

    2005-01-01

    A rice ( Oryza sativa L. ssp. japonica cv. Nipponbare) T-DNA tagged population consisting of about 7000 individual lines was generated and screened for rice lesion mimic mutants in the T1 generation. Ten lines were found to develop spontaneous lesions in the absence of pathogen infection and displayed distinct lesion phenotypes. These mutants were tentatively designated as lm1 -lm10 (for lesion mimic), respectively. Lesion formation of lm mutants was developmentally regulated, and all the mutants showed stunted growth and reduced fertility. Genetic analysis demonstrated that all the mutations were recessive, and five partially fertile mutants (lm4-lm8) were derived from different loci. Mimic lesions occurring on the leaves of lm mutants resulted from cell death as revealed by trypan blue staining. Six of them ( lm3 -lm8 ) exhibited enhanced resistance to five bacterial blight isolates, indicating their wide-spectrum resistance to this pathogen. These results imply that some lesion mimic mutations of rice might be involved in disease resistance signaling pathways,and that isolation of these mutated genes may be useful for elucidating molecular mechanisms of plant disease resistance. Among the mutants, only one mutant, lm6, was preliminarily shown to cosegregate with the inserted T-DNA in its T1 generation, making it feasible to isolate the gene responsible for the phenotype of this mutant.

  10. A Lesion-Mimic Syntaxin Double Mutant in Arabidopsis Reveals Novel Complexity of Pathogen Defense Signaling

    Institute of Scientific and Technical Information of China (English)

    Ziguo Zhang; Hans Thordal-Christensen; Andrea Lenk; Mats X. Andersson; Torben Gjetting; Carsten Pedersen; Mads E. Nielsen; Marl-Anne Newman; Bi-Huei Hou; Shauna C. Somerville

    2008-01-01

    The lesion-mimicArabidopsis mutant, syp121 syp122, constitutively expresses the salicylic acid (SA) signaling pathway and has low penetration resistance to powdery mildew fungi. Genetic analyses of the lesion-mimic phenotype have expanded our understanding of programmed cell death (PCD) in plants. Inactivation of SA signaling genes in syp121 syp 122 only partially rescues the lesion-mimic phenotype, indicating that additional defenses contribute to the PCD. Whole genome transcriptome analysis confirmed that SA-induced transcripts, as well as numerous other known pathogenresponse transcripts, are up-regulated after inactivation of the syntaxin genes. A suppressor mutant analysis of syp121 syp122 revealed that FMO1, ALD1, and PAD4 are important for lesion development. Mutant alleles of EDS1, NDR1, RAR1, and SGT1b also partially rescued the lesion-mimic phenotype, suggesting that mutating syntaxin genes stimulates TIR-NB-LRR and CC-NB-LRR-type resistances. The syntaxin double knockout potentiated a powdery mildewinduced HR-like response. This required functional PAD4 but not functional SA signaling. However, SA signaling potentiated the PAD4-dependent HR-like response. Analyses of quadruple mutants suggest that EDS5 and SID2 confer separate SA-independent signaling functions, and that FMO1 and ALD1 mediate SA-independent signals that are NPRl-dependent.These studies highlight the contribution of multiple pathways to defense and point to the complexity of their interactions.

  11. Synergistic Effect of MiR-146a Mimic and Cetuximab on Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Suning Huang

    2014-01-01

    Full Text Available Previously, we found that the expression of microRNA-146a (miR-146a was downregulated in hepatocellular carcinoma (HCC formalin-fixed paraffin-embedded (FFPE tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.

  12. Effect of the search image on the lizard ability to reveal a Batesian mimic

    OpenAIRE

    Beneš, Josef

    2016-01-01

    The effect of the search image on the ability of hand reared skinks (Chalcides sexlineatus) to reveal a "fake" Batesian mimic was tested with respect to their previous experience with palatable experimental prey (Guyana spotted cockroach Blaptica dubia) which served as a motivational prey as well as midsized mealworm beetle larvae (Tenebrio molitor). The red firebug (Pyrrhocoris apterus) was used as an aposematic model.

  13. Identification and Genetic Mapping of a Lesion Mimic Mutant in Rice

    Institute of Scientific and Technical Information of China (English)

    MA Jian-yang; CHEN Sun-lu; ZHANG Jian-hui; DONG Yan-jun; TENG Sheng

    2012-01-01

    A lesion mimic stripe mutant,designated as Ims1 (lesion mimic stripe 1),was obtained from the M2 progeny of a 60Co Y-radiation treated japonica rice variety Jiahua 1.The Ims1 mutant displayed propagation type lesions across the whole growth and developmental stages.Physiology and histochemistry analysis showed that the mutant exhibited a phenotype of white stripe when grown under high temperature (30 ℃),and the lesion mimic caused by programmed cell death under low temperature (20 ℃).The genetic analysis indicated that this lesion-mimic phenotype is controlled by a single locus recessive nuclear gene.Furthermore,by using simple sequence repeat markers and an F2 segregating population derived from two crosses of Ims1 × 93-11 and Ims1 × Pei'ai 64S,the Ims1 gene was mapped between markers Indel1 and MM0112-4 with a physical distance of 400 kb on chromosome 6 in rice.

  14. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

    Science.gov (United States)

    Fang, Jia; Liu, Ming-Sheng; Guan, Yu-Zhou; Du, Hua; Li, Ben-Hong; Cui, Bo; Ding, Qing-Yun; Cui, Li-Ying

    2016-01-01

    Background: Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. Methods: We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. Results: The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P SBMA patients was similar to that of the normal controls (P = 0.862). An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (≥4.5) were observed exclusively in the ALS patients. Conclusions: The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders. PMID:26996473

  15. Efficient Nuclear DNA Cleavage in Human Cancer Cells by Synthetic Bleomycin Mimics

    NARCIS (Netherlands)

    Li, Qian; van der Wijst, Monique G. P.; Kazemier, Hinke G.; Rots, Marianne G.; Roelfes, Gerard

    2014-01-01

    Iron complexes of N,N-bis(2-Pyridylmethyl)-N-bis(2-pyridyl)-methylamine (N4Py) have proven to be excellent synthetic mimics of the Bleomycins (BLMs), which are a family of natural antibiotics used clinically in the treatment of certain cancers. However, most investigations of DNA cleavage activity o

  16. The role of the hipermobile mimic muscules of midle face on the postrhinoplastic results

    Directory of Open Access Journals (Sweden)

    Hayk D. Yenokyan

    2011-05-01

    Full Text Available In article questions of influence of mimic muscles on the remote results ринопластических operations are considered. Use Botox (botulotoxin type A for improvement of results rhinoplasties.

  17. Recent advances in compartmentalized synthetic architectures as drug carriers, cell mimics and artificial organelles

    DEFF Research Database (Denmark)

    York-Durán, María José; Gallardo, Maria Godoy; Labay, Cédric Pierre

    2017-01-01

    significant research attention and these assemblies are proposed as candidate materials for a range of biomedical applications. In this Review article, the recent successes of multicompartment architectures as carriers for the delivery of therapeutic cargo or the creation of micro- and nanoreactors that mimic...

  18. Genetics of superoxide dismutase in the forest tent caterpillar and other organisms.

    Science.gov (United States)

    Lorimer, N

    1979-01-01

    The electrophoretic assay of superoxide dismutase (SOD) in Malacosoma disstria revealed a total of 13 bands arranged in 9 patterns. One locus, composed of bands 28, 32, 36 was polymorphic in some locations. Band frequencies varied by location, but not by generation or by time in the laboratory. Significant interactions between sibling groups and SOD types for development time suggest that selective advantage is a function of genetic background. SOD, an important enzyme protecting diverse organisms against the toxic radicals of oxygen, has been extensively analyzed by biochemists. Geneticists have assayed individuals and populations for the smae enzyme, calling it tetrazolium oxidase (TO). The biochemistry and genetics literatures were reviewed and results from the two disciplines were discussed.

  19. Activity and stability of recombinant human superoxide dismutase in buffer solutions and hypothermic perfusates.

    Directory of Open Access Journals (Sweden)

    Senoo,Yoshimasa

    1988-06-01

    Full Text Available The stability of recombinant human superoxide dismutase (r-hSOD in buffer solutions was studied in solutions at various pH and temperatures. Additionally, we studied the effects of incubation with proteases, serum and two types of hypothermic perfusates. R-hSOD was stable in the pH range of 6-11 and at temperatures up to 80 degrees C for 30 min. R-hSOD activity was not affected by incubation with trypsin, aminopeptidase M or serum for 2 h. R-hSOD activity determined at various temperatures (4-37 degrees C did not vary remarkably. R-hSOD in hypothermic perfusates was stable at 4-37 degrees C for 24 h.

  20. Substituent Effect on Proton Affinity of Imidazole in Cu,Zn-Superoxide Dismutase

    Institute of Scientific and Technical Information of China (English)

    JI Hong-Fang; ZHANG Hong-Yu

    2006-01-01

    To investigate whether the proton-accepting ability of imidazole in Cu,Zn-superoxide dismutase (SOD) was possibly modulated by Zn(Ⅱ) or not, the proton affinity (Ap) of N3 in imidazole group was calculated by density functional theory (DFF) with B3LYP functional. It was found that Zn(Ⅱ) attenuates the Ap, because of its electron-withdrawing effect, while the three ligands connected with Zn(Ⅱ) (residues of two His and one Asp) exert an opposite effect, owing to their electron-donating ability. This finding suggested that the three ligands should play a role in the normal function of Cu,Zn-SOD and should be taken into consideration in the future study.

  1. PEA chloroplasts under clino-rotation: lipid peroxidation and superoxide dismutase activity

    Science.gov (United States)

    Baranenko, V. V.

    The lipid peroxidation (LP) intensity and the activity of the antioxidant enzyme superoxide dismutase (SOD) were studied in chloroplasts of pea (Pisum sativum L.) plants grown for 7 and 14 days under clino-rotation. An increase in LP levels in chloroplasts during both terms of clinorotation in comparison with stationary controls was documented. SOD activity increased in chloroplasts of plants that were clino-rotated for seven days. SOD has a significant protective effect by diminishing the availability of O2-. However, under more prolonged clino-rotation (14 days), SOD activity decreased but was still higher than in the control samples. In accordance with Selye's oxidative stress theory (Selye, 1956; modified by Leshem et al., 1998), plants that were clino-rotated for seven days are presumed to be in a stage of resistance while 14-day plants reached a stage of exhaustion.

  2. Chemical Modification of Tryptophan Residues in Superoxide Dismutase from Camellia Pollen and Its Fluorescence Spectrum

    Institute of Scientific and Technical Information of China (English)

    HE Xiao-hong; WU Min; LI Shan-yu; CHU Yu-zhuo; CHEN Jia; LIU Lan-ying

    2005-01-01

    The amino acid composition of the superoxide dismutase(SOD) from camellia pollen was measured and the tryptophan(Trp) residues were modified by using N-bromosuccinimide(NBS). The results show that there are 21 Trp residues in an SOD molecule and seven of which are located on the surface of the enzyme. By researching the fluorescence spectra of the native SOD and the modified SOD, we have found that the emission wavelength of Trp is at 335 nm and the fluorescence intensity will decrease when the enzyme is modified. The results also show that potassium iodide(KI) can significantly quench the fluorescence of the native SOD, but it has a less pronounced effect on the modified enzyme. Glycerin as a surface activation reagent can stabilize the fluorescence of the modified enzyme.

  3. Serum and Ascitic Fluid Superoxide Dismutase and Malondialdehyde Levels in Patients with Cirrhosis

    Directory of Open Access Journals (Sweden)

    Ugur Coskun

    2008-01-01

    Full Text Available Serum and ascitic fluid superoxide dismutase (SOD and malondialdehyde (MDA levels were measured in 43 patients with cirrhosis and in a 10 healthy control group. Compensated cirrhotic patients had no clinically detectable ascites, but decompensated patients had massive ascites. Cirrhotic patients were divided into three groups: patients with compensated cirrhosis (n = 16, patients with decompensated cirrhosis with Spontaneous bacterial peritonitis (SBP (n = 14, and patients with decompensated cirrhosis without SBP (n = 13. All cirrhotic patients in the experimental group had significantly higher serum SOD (p 0.05. These results suggest that the increase in serum SOD and MDA levels are not related to the presence of SBP and the status of liver cirrhosis. To sum up, clarifying the impact of increased serum SOD and MDA levels in cirrhotic patients needs further investigation.

  4. [Free radicals of oxygen and superoxide dismutase. Biological and medical aspects].

    Science.gov (United States)

    Monte, M; Sacerdote de Lustig, E

    1994-01-01

    Oxygen free radicals (OFR) are very reactive and unstable metabolites capable of altering important biomolecules including proteins, lipids and nucleic acids. OFR are regulated by enzymes such as superoxide dismutases (SOD), catalase, glutation peroxidase and by molecules such as vitamins E, A, C, and K, selenio, cystein and other compounds. Increased OFR levels due to an overproduction of these metabolites or to a failure in the control system, induce cellular and tissue injuries that could lead to diseases such as atherosclerosis, arthritis, fibrosis, lung and heart injuries, neurological disorders and cancer. In this article we consider the use of SOD as therapeutic agents both in human and experimental models. We also refer to the administration of SOD as a protective factor against secondary injuries during radiotherapy and to the determination of SOD as a tumor marker.

  5. Expression of Mn-Superoxide Dismutase Gene in Nontumorigenic and Tumorigenic Human Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Sutapa Mukhopadhyay

    2004-01-01

    Full Text Available Manganese superoxide dismutase (Mn-SOD, localized at the mitochondrial matrix, has the ability to protect cells against oxidative damage. It has been reported that low levels of Mn-SOD gene expression cause the development of certain kind of tumors. On the other hand, overexpression of Mn-SOD gene may play an important role in the development of cancer. In our study, we find that Mn-SOD activity was higher in nonaggressive (MCF-7 and aggressive (BT-549 and 11-9-14 breast cancer cell lines compared to that of nontumorigenic (MCF-12A and MCF-12F mammary epithelial cell lines. We also observed an increased expression of Mn-SOD gene in cancerous cell lines. The elevated level of SOD activity in nonaggressive and aggressive breast epithelial cell lines was associated with some changes in nucleotide sequence.

  6. Endogenous antioxidant defense induction by melon superoxide dismutase reduces cardiac hypertrophy in spontaneously hypertensive rats.

    Science.gov (United States)

    Carillon, Julie; Rugale, Caroline; Rouanet, Jean-Max; Cristol, Jean-Paul; Lacan, Dominique; Jover, Bernard

    2014-08-01

    We assessed the influence of SODB, a melon superoxide dismutase (SOD), on left ventricular (LV) hypertrophy in SHR. SODB (4 or 40U SOD) was given orally for 4 or 28 days to SHR. For each treatment period, LV weight index (LVWI) and cardiomyocytes size were measured. SOD, glutathione peroxidase (GPx) and catalase expressions, and LV production and presence of superoxide anion were determined. Pro-inflammatory markers were also measured. SODB reduced LVWI and cardiomyocytes size after 4 or 28 days. Cardiac SOD and GPx increased by 30-40% with SODB. The presence but not production of superoxide anion was significantly reduced by SODB. No effect of SODB was detected on inflammatory status in any group. The beneficial effect of SODB on cardiac hypertrophy seems to be related to the stimulation of endogenous antioxidant defense, suggesting that SODB may be of interest as a dietary supplementation during conventional antihypertensive therapy.

  7. LC-MS/MS Analysis Unravels Deep Oxidation of Manganese Superoxide Dismutase in Kidney Cancer

    Science.gov (United States)

    Zhao, Zuohui; Azadzoi, Kazem M.; Choi, Han-Pil; Jing, Ruirui; Lu, Xin; Li, Cuiling; Wang, Fengqin; Lu, Jiaju; Yang, Jing-Hua

    2017-01-01

    Manganese superoxide dismutase (MNSOD) is one of the major scavengers of reactive oxygen species (ROS) in mitochondria with pivotal regulatory role in ischemic disorders, inflammation and cancer. Here we report oxidative modification of MNSOD in human renal cell carcinoma (RCC) by the shotgun method using data-dependent liquid chromatography tandem mass spectrometry (LC-MS/MS). While 5816 and 5571 proteins were identified in cancer and adjacent tissues, respectively, 208 proteins were found to be up- or down-regulated (p kidney cancer due to modifications. Thus, LC-MS/MS analysis revealed multiple oxidative modifications of MNSOD at different amino acid residues that might mediate the regulation of the superoxide radicals, mitochondrial ROS scavenging and MNSOD activity in kidney cancer. PMID:28165386

  8. Effects of Several Pesticides on Superoxide Dismutase (SOD) Activities of Different Rice Varieties

    Institute of Scientific and Technical Information of China (English)

    WU Jin-cai; LIU Jing-lan; SHEN Ying-chun; XU Jian-xiang; JINAG Yong-hou; XU Su-xia

    2002-01-01

    Effects of several pesticides on superoxide dismutase (SOD) activities of different rice varieties were studied. The results showed that SOD activities of almost all the herbicide treatments on different rice varieties increased during 15 days after treatment (DAT). SOD activity of rice plants reached a maximum at 10DAT, began to decline at 15 DAT and then recovered to the control level at 21 DAT. The SOD activity of rice plants at 2 days after the second application of pesticides (spraying with insecticide-bisultap or fungicide-jingganmycin at 22 days after herbicide treatments) (2 DAST) increased and declined at 6 DAST in comparison with that of the control, indicating that two applications of pesticides had a more serious impact on rice plants compared with one application. SOD activity of rice plants may be an index of rice plant resistance.

  9. Therapeutic value of oral supplementation with melon superoxide dismutase and wheat gliadin combination.

    Science.gov (United States)

    Romao, Susana

    2015-03-01

    Dietary antioxidant supplementation has been popular in Western countries. Various supplements have been developed in recent years, and research has been gathered from both animal and clinical research trials. In this review, the therapeutic value of oral administration of a combination of melon superoxide dismutase (SOD) and a vegetable polymer (gliadin) is evaluated. Critical examination of the effects of SOD-gliadin supplementation is carried out, with an emphasis on its impact on oxidative stress levels and on endogenous antioxidant pathways. Overall analysis of peer-reviewed published data suggests that intake of SOD-gliadin might have advantageous health effects. These conclusions are dependent on the condition or pathology under consideration. In general, the authors, who analyzed SOD-gliadin supplementation, support the use of SOD-gliadin supplementation as a complementary treatment rather than a therapeutic treatment. To further clarify the importance of dietary SOD-gliadin administration, additional large-scale clinical trials are recommended.

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

    Science.gov (United States)

    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.

  11. Evaluation of Malondialdehyde, Superoxide Dismutase and Catalase Activity in Fetal Cord Blood of Depressed Mothers

    Science.gov (United States)

    Camkurt, Mehmet Akif; Fındıklı, Ebru; Bakacak, Murat; Tolun, Fatma İnanç; Karaaslan, Mehmet Fatih

    2017-01-01

    Objective The umbilical cord consists of two arteries and one vein and it functions in the transport between the maternal and fetal circulation. Biochemical analysis of fetal cord blood (FCB) during delivery could be beneficial in terms of understanding the fetal environment. In this study, we aimed to investigate oxidative parameters like malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in FCB during delivery. Methods We collected FCB samples during caesarean section. Our study included 33 depressed mothers and 37 healthy controls. We investigated MDA, SOD, and CAT levels in FCB samples. Results We found no significant difference between groups in terms of MDA (p=0.625), SOD (p=0.940), and CAT (p=0.413) levels. Conclusion Our study reveals probable protective effects of the placenta from oxidative stress. Future studies should include larger samples. PMID:28138108

  12. ENVIRONMENTAL EFFECTS ON SUPEROXIDE DISMUTASE AND CATALASE ACTIVITY AND EXPRESSION IN HONEY BEE.

    Science.gov (United States)

    Nikolić, Tatjana V; Purać, Jelena; Orčić, Snežana; Kojić, Danijela; Vujanović, Dragana; Stanimirović, Zoran; Gržetić, Ivan; Ilijević, Konstantin; Šikoparija, Branko; Blagojević, Duško P

    2015-12-01

    Understanding the cellular stress response in honey bees will significantly contribute to their conservation. The aim of this study was to analyze the response of the antioxidative enzymes superoxide dismutase and catalase in honey bees related to the presence of toxic metals in different habitats. Three locations were selected: (i) Tunovo on the mountain Golija, as control area, without industry and large human impact, (ii) Belgrade as urban area, and (iii) Zajača, as mining and industrial zone. Our results showed that the concentrations of lead (Pb) in whole body of bees vary according to habitat, but there was very significant increase of Pb in bees from investigated industrial area. Bees from urban and industrial area had increased expression of both Sod1 and Cat genes, suggesting adaptation to increased oxidative stress. However, in spite increased gene expression, the enzyme activity of catalase was lower in bees from industrial area suggesting inhibitory effect of Pb on catalase.

  13. Effect of local application of superoxide dismutase on dielectric parameters of cooled skin in rats.

    Science.gov (United States)

    Paramonov, B A; Turkovski, I I; Doroshkevich, O S; Taranova, V N; Pomorski, K P

    2008-11-01

    The effect of on Changes in dielectric parameters of the skin (modulus of complex dielectric permittivity |e| and dielectric loss tangent tgd) were studied on rats with local surface contact cooling followed by treatment with various cream formulations. Addition of antioxidant superoxide dismutase (SOD) to the cream significantly prevented the shifts in these parameters, which attested to less pronounced changes in the water balance in SOD-treated skin. Application of SOD during the early terms after cooling accelerated wound healing. Histological examination performed on posttraumatic day 60 revealed better integrity of the skin structures (hair follicle, sweat and sebaceous gland), which indicates ability of SOD to prevent and ameliorate the degree of cold-induced damage in the skin.

  14. Dynamical Transition of Myoglobin and Cu/Zn Superoxide Dismutase Revealed by Molecular Dynamics Simulation

    Institute of Scientific and Technical Information of China (English)

    张莉莉; 张建华; 周林祥

    2002-01-01

    We have carried out parallel molecular dynamics simulations of solvated and non-solvated myoglobin and solvated Cu/Zn superoxide dismutase at different temperatures. By analysis of several methods, the simulations reproduce the quasielastic neutron scattering experimental results. Below 200 K these two proteins behave as harmonic solids with essentially only vibrational motion, while above this temperature, there is a striking dynamic transition into anharmonic motion. Moreover, the simulations further show that water molecules play an important role for this dynamical transition. There is no such sharp dynamical transition in non-solvated proteins and the higher the solvate density is, the steeper at transition point the curve of mean square displacement versus temperature will be. The simulations also display that the dynamical transition is a general property for globular protein and this transition temperature is a demarcation of enzyme activity.

  15. Transient structural distortion of metal-free Cu/Zn superoxide dismutase triggers aberrant oligomerization

    DEFF Research Database (Denmark)

    Teilum, Kaare; Smith, Melanie H; Schulz, Eike

    2009-01-01

    of the excited-state structure that forms intermolecular contacts in the earliest nonnative dimer/oligomer. The conformational transition that triggers oligomerization is a common feature of WT SOD1 and ALS-associated mutants that have widely different physicochemical properties. But compared with WT SOD1......, the mutants have enhanced structural distortions in their excited states, and in some cases slightly higher excited-state populations and lower kinetic barriers, implying increased susceptibility to oligomerization. Our results provide a unified picture that highlights both (i) a common denominator among......Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease linked to the misfolding of Cu/Zn superoxide dismutase (SOD1). ALS-related defects in SOD1 result in a gain of toxic function that coincides with aberrant oligomerization. The structural events triggering oligomerization have...

  16. Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01.

    Directory of Open Access Journals (Sweden)

    Anton N Chikaev

    Full Text Available The ability to induce anti-HIV-1 antibodies that can neutralize a broad spectrum of viral isolates from different subtypes seems to be a key requirement for development of an effective HIV-1 vaccine. The epitopes recognized by the most potent broadly neutralizing antibodies that have been characterized are largely discontinuous. Mimetics of such conformational epitopes could be potentially used as components of a synthetic immunogen that can elicit neutralizing antibodies. Here we used phage display technology to identify peptide motifs that mimic the epitope recognized by monoclonal antibody VRC01, which is able to neutralize up to 91% of circulating primary isolates. Three rounds of biopanning were performed against 2 different phage peptide libraries for this purpose. The binding specificity of selected phage clones to monoclonal antibody VRC01 was estimated using dot blot analysis. The putative peptide mimics exposed on the surface of selected phages were analyzed for conformational and linear homology to the surface of HIV-1 gp120 fragment using computational analysis. Corresponding peptides were synthesized and checked for their ability to interfere with neutralization activity of VRC01 in a competitive inhibition assay. One of the most common peptides selected from 12-mer phage library was found to partially mimic a CD4-binding loop fragment, whereas none of the circular C7C-mer peptides was able to mimic any HIV-1 domains. However, peptides identified from both the 12-mer and C7C-mer peptide libraries showed rescue of HIV-1 infectivity in the competitive inhibition assay. The identification of epitope mimics may lead to novel immunogens capable of inducing broadly reactive neutralizing antibodies.

  17. Extracellular superoxide dismutase protects Histoplasma yeast cells from host-derived oxidative stress.

    Directory of Open Access Journals (Sweden)

    Brian H Youseff

    Full Text Available In order to establish infections within the mammalian host, pathogens must protect themselves against toxic reactive oxygen species produced by phagocytes of the immune system. The fungal pathogen Histoplasma capsulatum infects both neutrophils and macrophages but the mechanisms enabling Histoplasma yeasts to survive in these phagocytes have not been fully elucidated. We show that Histoplasma yeasts produce a superoxide dismutase (Sod3 and direct it to the extracellular environment via N-terminal and C-terminal signals which promote its secretion and association with the yeast cell surface. This localization permits Sod3 to protect yeasts specifically from exogenous superoxide whereas amelioration of endogenous reactive oxygen depends on intracellular dismutases such as Sod1. While infection of resting macrophages by Histoplasma does not stimulate the phagocyte oxidative burst, interaction with polymorphonuclear leukocytes (PMNs and cytokine-activated macrophages triggers production of reactive oxygen species (ROS. Histoplasma yeasts producing Sod3 survive co-incubation with these phagocytes but yeasts lacking Sod3 are rapidly eliminated through oxidative killing similar to the effect of phagocytes on Candida albicans yeasts. The protection provided by Sod3 against host-derived ROS extends in vivo. Without Sod3, Histoplasma yeasts are attenuated in their ability to establish respiratory infections and are rapidly cleared with the onset of adaptive immunity. The virulence of Sod3-deficient yeasts is restored in murine hosts unable to produce superoxide due to loss of the NADPH-oxidase function. These results demonstrate that phagocyte-produced ROS contributes to the immune response to Histoplasma and that Sod3 facilitates Histoplasma pathogenesis by detoxifying host-derived reactive oxygen thereby enabling Histoplasma survival.

  18. Six-coordinate manganese(3+) in catalysis by yeast manganese superoxide dismutase

    Energy Technology Data Exchange (ETDEWEB)

    Sheng, Yuewei; Gralla, Edith Butler; Schumacher, Mikhail; Cascio, Duilio; Cabelli, Diane E.; Valentine, Joan Selverstone (EWHA); (UCLA); (BNL)

    2012-10-10

    Reduction of superoxide (O{sub 2}{sup -}) by manganese-containing superoxide dismutase occurs through either a 'prompt protonation' pathway, or an 'inner-sphere' pathway, with the latter leading to formation of an observable Mn-peroxo complex. We recently reported that wild-type (WT) manganese superoxide dismutases (MnSODs) from Saccharomyces cerevisiae and Candida albicans are more gated toward the 'prompt protonation' pathway than human and bacterial MnSODs and suggested that this could result from small structural changes in the second coordination sphere of manganese. We report here that substitution of a second-sphere residue, Tyr34, by phenylalanine (Y34F) causes the MnSOD from S. cerevisiae to react exclusively through the 'inner-sphere' pathway. At neutral pH, we have a surprising observation that protonation of the Mn-peroxo complex in the mutant yeast enzyme occurs through a fast pathway, leading to a putative six-coordinate Mn3+ species, which actively oxidizes O{sub 2}{sup -} in the catalytic cycle. Upon increasing pH, the fast pathway is gradually replaced by a slow proton-transfer pathway, leading to the well-characterized five-coordinate Mn{sup 3+}. We here propose and compare two hypothetical mechanisms for the mutant yeast enzyme, diffeeing in the structure of the Mn-peroxo complex yet both involving formation of the active six-coordinate Mn{sup 3+} and proton transfer from a second-sphere water molecule, which has substituted for the -OH of Tyr34, to the Mn-peroxo complex. Because WT and the mutant yeast MnSOD both rest in the 2+ state and become six-coordinate when oxidized up from Mn{sup 2+}, six-coordinate Mn{sup 3+} species could also actively function in the mechanism of WT yeast MnSODs.

  19. Studies on superoxide dismutase activities in virulent and avirulent strains of Agrobacterium tumefaciens and also in normal and crown gall tumor cells of Bryophyllum calycinum.

    Science.gov (United States)

    Banerjee, D; Basu, M; Choudhury, I; Chatterjee, G C

    1982-01-01

    Superoxide dismutase activity in virulent strains of Agrobacterium tumefaciens was found to be higher than that in avirulent strains. Polyacrylamide gel electrophoresis revealed two isoenzymes in both these strains. These isoenzymes are suggested to be iron and manganese containing superoxide dismutases. Crown gall tumor cells of the plant Bryophyllum calycinum were found to have higher superoxide dismutase activity than the normal plant cells. Polyacrylamide gel electrophoresis revealed two isoenzymes in both normal and crown gall tumor cells. Advantages of the higher superoxide dismutase activities in respect of the survival of virulent strains of A. tumefaciens and crown gall tumor growth have been discussed.

  20. Molecular cloning and characterization of a cytoplasmic manganese superoxide dismutase and a mitochondrial manganese superoxide dismutase from Chinese mitten crab Eriocheir sinensis.

    Science.gov (United States)

    Wang, Mengqiang; Wang, Lingling; Yi, Qilin; Gai, Yunchao; Song, Linsheng

    2015-11-01

    Superoxide dismutase (SOD) functions as the first and essential enzyme in the antioxidant system and is ubiquitously existed in both prokaryotes and eukaryotes. In the present study, both cytoplasmic and mitochondrial manganese SOD were identified from Chinese mitten crab Eriocheir sinensis (designed as EscytMnSOD and EsmtMnSOD). The complete nucleotide sequence of EscytMnSOD comprised 1349 bp and consisted of a 5' untranslated regions (UTR) of 43 bp, a 3' UTR of 445 bp and an open reading frame (ORF) of 861 bp encoding a polypeptide of 286 amino acid residues. The full-length cDNA sequence of EsmtMnSOD comprised 990 bp, containing a 5' UTR of 55 bp, a 3' UTR of 278 bp and an ORF of 657 bp encoding a polypeptide of 218 amino acid residues. The deduced amino acid sequences of EscytMnSOD and EsmtMnSOD contained highly conserved MnSOD signature and typical functional domain, and exhibited high similarity with their reported homologues. In the phylogenetic tree, EscytMnSOD and EsmtMnSOD were clustered with their homologues from the land crab Cardisoma armatum. The EscytMnSOD and EsmtMnSOD transcripts were constitutively expressed in haemocytes, muscle, heart, gill, haepatopancreas and gonad, with the highest expression level in gills and haepatopancreas, respectively. The mRNA expression levels of them were all up-regulated in haemocytes with similar profiles after the stimulation of Vibrio anguillarum, Micrococcus luteus and Pichia pastoris. The EsmtMnSOD with low basal expression level responded to invading microbes intensely, while the EscytMnSOD with high basal expression level exhibited mild responses against stimulating microbes. The purified rEscytMnSOD and rEsmtMnSOD proteins exhibited specific Mn(2+)-dependent enzymatic activities, while rEscytMnSOD with lower basic activity displayed higher stability than rEsmtMnSOD. All these results indicated that EscytMnSOD and EsmtMnSOD were efficiently antioxidant enzymes and potentially involved in the innate immune

  1. Synthesis of triazole-nucleoside phosphoramidites and their use in solid-phase oligonucleotide synthesis.

    Science.gov (United States)

    Peel, Brandon J; Efthymiou, Tim C; Desaulniers, Jean-Paul

    2014-12-19

    Triazole-backbone oligonucleotides are macromolecules that have one or more triazole units that are acting as a backbone mimic. Triazoles within the backbone have been used within oligonucleotides for a variety of applications. This unit describes the preparation and synthesis of two triazole-nucleoside phosphoramidites [uracil-triazole-uracil (UtU) and cytosine-triazole-uracil (CtU)] based on a PNA-like scaffold, and their incorporation within oligonucleotides.

  2. Stereoselective synthesis of conformationally constrained cyclohexanediols: a set of molecular scaffolds for the synthesis of glycomimetics.

    Science.gov (United States)

    Bernardi, A; Arosio, D; Manzoni, L; Micheli, F; Pasquarello, A; Seneci, P

    2001-09-21

    The practical, stereoselective synthesis of the three diastereoisomeric 1,2-trans-dicarboxy-4,5-cyclohexanediols 1-3 (DCCHDs) is described, starting from a common precursor, easily available in both enantiomeric forms. The regioselective derivatization of all functional groups of 1 is also reported. The three DCCHDs are locked in a single chair conformation and thus can be used to mimic vicinally disubstituted monosaccharides of any relative configuration.

  3. Involvement of Extracellular Cu/Zn Superoxide Dismutase in Cotton Fiber Primary and Secondary Cell Wall Biosynthesis

    Science.gov (United States)

    Extracellular Cu/Zn superoxide dismutases (CSDs) that catalyze the conversion of superoxide to hydrogen peroxide have been suggested to be involved in lignification of secondary walls in spinach, pine and aspen. In cotton fibers, hydrogen peroxide was proposed to be involved in the induction of seco...

  4. Crystal Structure of Cu/Zn Superoxide Dismutase from Taenia Solium Reveals Metal-mediated Self-assembly

    Energy Technology Data Exchange (ETDEWEB)

    A Hernandez-Santoyo; A Landa; E Gonzalez-Mondragon; M Pedraza-Escalona; R Parra-Unda; A Rodriguez-Romero

    2011-12-31

    Taenia solium is the cestode responsible for porcine and human cysticercosis. The ability of this parasite to establish itself in the host is related to its evasion of the immune response and its antioxidant defence system. The latter includes enzymes such as cytosolic Cu/Zn superoxide dismutase. In this article, we describe the crystal structure of a recombinant T. solium Cu/Zn superoxide dismutase, representing the first structure of a protein from this organism. This enzyme shows a different charge distribution at the entrance of the active channel when compared with human Cu/Zn superoxide dismutase, giving it interesting properties that may allow the design of specific inhibitors against this cestode. The overall topology is similar to other superoxide dismutase structures; however, there are several His and Glu residues on the surface of the protein that coordinate metal ions both intra- and intermolecularly. Interestingly, one of these ions, located on the {beta}2 strand, establishes a metal-mediated intermolecular {beta}-{beta} interaction, including a symmetry-related molecule. The factors responsible for the abnormal protein-protein interactions that lead to oligomerization are still unknown; however, high metal levels have been implicated in these phenomena, but exactly how they are involved remains unclear. The present results suggest that this structure could be useful as a model to explain an alternative mechanism of protein aggregation commonly observed in insoluble fibrillar deposits.

  5. Ceruloplasmin levels and erythrocyte superoxide dismutase activity in small preterm infants during the early anemia of prematurity.

    Science.gov (United States)

    Hågå, P

    1981-11-01

    Ceruloplasmin plasma levels and erythrocyte superoxide dismutase activity were studied in appropriate for gestational age preterm infants (birth weights less than or equal to 1500 g) during the first 10 weeks of life. Preterm infants had significantly lower ceruloplasmin concentrations in cord blood than term infants, the mean level in the preterm infants being 0.07 g/l. At 1 week of age ceruloplasmin levels had risen significantly, whereupon a fall occurred at 2 weeks of age. Ceruloplasmin concentrations increased slowly and progressively from 4 weeks of age. The low ceruloplasmin concentration during the early anemia of prematurity seems not to interfere with iron mobilization. The superoxide dismutase activity per gram hemoglobin in cord blood erythrocytes from normal term infants was significantly lower than that of red blood cells from adults. When the activity was expressed per erythrocyte no difference was found. The normochromic macrocytic red blood cells of the neonate most likely explain this discrepancy. The erythrocyte superoxide dismutase activity of the preterm infants did not change from birth until 10 weeks of age, and the levels seemed adequate judged from the levels found in red blood cells from adults and cord blood from term infants. Neither ceruloplasmin nor erythrocyte superoxide dismutase activity seem to play a role in the etiology of the early anemia of prematurity.

  6. STRESS-RESPONSE IN LACTOCOCCUS-LACTIS - CLONING, EXPRESSION ANALYSIS, AND MUTATION OF THE LACTOCOCCAL SUPEROXIDE-DISMUTASE GENE

    NARCIS (Netherlands)

    SANDERS, JW; LEENHOUTS, KJ; HAANDRIKMAN, AJ; VENEMA, G; KOK, J

    1995-01-01

    In an analysis of the stress response of Lactococcus lactis, three proteins that were induced under low pH culture conditions were detected. One of these was identified as the lactococcal superoxide dismutase (SodA) by N-terminal amino acid sequence analysis. The gene encoding this protein, designat

  7. A plant tendril mimic soft actuator with phototunable bending and chiral twisting motion modes

    Science.gov (United States)

    Wang, Meng; Lin, Bao-Ping; Yang, Hong

    2016-12-01

    In nature, plant tendrils can produce two fundamental motion modes, bending and chiral twisting (helical curling) distortions, under the stimuli of sunlight, humidity, wetting or other atmospheric conditions. To date, many artificial plant-like mechanical machines have been developed. Although some previously reported materials could realize bending or chiral twisting through tailoring the samples into various ribbons along different orientations, each single ribbon could execute only one deformation mode. The challenging task is how to endow one individual plant tendril mimic material with two different, fully tunable and reversible motion modes (bending and chiral twisting). Here we show a dual-layer, dual-composition polysiloxane-based liquid crystal soft actuator strategy to synthesize a plant tendril mimic material capable of performing two different three-dimensional reversible transformations (bending versus chiral twisting) through modulation of the wavelength band of light stimuli (ultraviolet versus near-infrared). This material has broad application prospects in biomimetic control devices.

  8. Idiopathic Hypertrophic Pyloric Stenosis in an Adult, a Potential Mimic of Gastric Carcinoma

    Directory of Open Access Journals (Sweden)

    Alireza Zarineh

    2010-01-01

    Full Text Available Primary or idiopathic hypertrophy of the pyloric muscle (IHPM is a rare entity with uncertain pathogenesis which both clinically and pathologically mimics gastric cancer. We present a rare late-occurring case of IHPM in a 71-year-old Caucasian man with no apparent predisposing factor. Imaging studies demonstrated gastric distension with air fluid levels and no evidence of extrinsic compression. At upper endoscopy, massive gastric distension and no evidence of any ulcer or other mucosal defects were observed. Microscopically, marked hypertrophy of muscularis mucosa with smooth muscle cells arranged in whorls and fascicles was present which gradually transitioned to normal areas. The muscle fibers stained with smooth muscle actin and trichrome stain highlighted fibrosis between the muscle fibers. Although uncommon, IHPM can clinically and histologically mimic other proliferations in the gastric wall, such as gastrointestinal stromal tumor or a spindle cell neoplasm. The recent advances in understanding the pathogenesis of IHPM are discussed.

  9. How well does cholesteryl hemisuccinate mimic cholesterol in saturated phospholipid bilayers?

    DEFF Research Database (Denmark)

    Kulig, W.; Tynkkynen, J.; Javanainen, M.

    2014-01-01

    Cholesteryl hemisuccinate is a detergent that is often used to replace cholesterol in crystallization of membrane proteins. Here we employ atomistic molecular dynamics simulations to characterize how well the properties of cholesteryl hemisuccinate actually match those of cholesterol in saturated...... protein-free lipid membranes. We show that the protonated form of cholesteryl hemisuccinate mimics many of the membrane properties of cholesterol quite well, while the deprotonated form of cholesteryl hemisuccinate is less convincing in this respect. Based on the results, we suggest that cholesteryl...... hemisuccinate in its protonated form is a quite faithful mimic of cholesterol for membrane protein crystallization, if specific cholesterol-protein interactions (not investigated here) are not playing a crucial role....

  10. Cloning and Expressing of a Gene Encoding Cytosolic Copper/Zinc Superoxide Dismutase in the Upland Cotton

    Institute of Scientific and Technical Information of China (English)

    HU Gen-hai; YU Shu-xun; FAN Shu-li; SONG Mei-zhen

    2007-01-01

    In this study, a gene encoding a superoxide dismutase (SOD) was cloned from senescent leaves of cotton (Gossypium hirsutum), and its expressing profile was analyzed. The gene was cloned by rapid amplification of cDNA ends (RACE)method. Northern blotting was used to show the profile of the gene expression, and the enzyme activity was mensurated by NBT deoxidization method in different growth periods. The full length of a gene of cytosolic copper/zinc superoxide dismutase (Cu/Zn-SOD) was isolated from cotton (GenBank Accession Number: DQ445093). The sequence of cDNA contained 682 bp, the opening reading frame 456 bp, and encoded polypeptide 152 amino acids with the predicted molecular mass of 15.03 kD and theoretical pI of 6.09. The amino acid sequence was similar with the other plants from 82 to 87%. Southern blotting showed that the gene had different number of copies in different cotton species. Northern blotting suggested that the gene had different expression in different tissues and development stages. The enzyme activity was the highest in peak flowering stage. The cotton cytosolic (Cu/Zn-SOD) had lower copies in the upland cotton. The copper/zinc superoxide dismutase mRNA expressing level showed regular changing in the whole development stages; it was lower in the former stages, higher in latter stages and the highest at the peak flowering stage. The curve of the copper/zinc superoxide dismutase mRNA expressing level was consistent with that of the Cu/Zn-SOD enzyme activity.The copper/zinc superoxide dismutase mRNA expressing levels of different organs showed that the gene was higher in the root, leaf, and lower in the flower.

  11. Chemical UV Filters Mimic the Effect of Progesterone on Ca(2+) Signaling in Human Sperm Cells

    DEFF Research Database (Denmark)

    Rehfeld, A; Dissing, S; Skakkebæk, N E

    2016-01-01

    Progesterone released by cumulus cells surrounding the egg induces a Ca(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca(2+) channel and controls multiple Ca(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic...... competitively inhibited progesterone-induced Ca(2+) signals. In vivo exposure studies are needed to investigate whether UV filter exposure affects human fertility....

  12. Artificial cell mimics as simplified models for the study of cell biology.

    Science.gov (United States)

    Salehi-Reyhani, Ali; Ces, Oscar; Elani, Yuval

    2017-07-01

    Living cells are hugely complex chemical systems composed of a milieu of distinct chemical species (including DNA, proteins, lipids, and metabolites) interconnected with one another through a vast web of interactions: this complexity renders the study of cell biology in a quantitative and systematic manner a difficult task. There has been an increasing drive towards the utilization of artificial cells as cell mimics to alleviate this, a development that has been aided by recent advances in artificial cell construction. Cell mimics are simplified cell-like structures, composed from the bottom-up with precisely defined and tunable compositions. They allow specific facets of cell biology to be studied in isolation, in a simplified environment where control of variables can be achieved without interference from a living and responsive cell. This mini-review outlines the core principles of this approach and surveys recent key investigations that use cell mimics to address a wide range of biological questions. It will also place the field in the context of emerging trends, discuss the associated limitations, and outline future directions of the field. Impact statement Recent years have seen an increasing drive to construct cell mimics and use them as simplified experimental models to replicate and understand biological phenomena in a well-defined and controlled system. By summarizing the advances in this burgeoning field, and using case studies as a basis for discussion on the limitations and future directions of this approach, it is hoped that this minireview will spur others in the experimental biology community to use artificial cells as simplified models with which to probe biological systems.

  13. Biomolecular Programming of Discrete Nanomaterials for Sensors, Templates and Mimics of Natural Nanoscale Assemblies

    Science.gov (United States)

    2016-10-17

    AFRL-AFOSR-VA-TR-2016-0343 BIOMOLECULAR PROGRAMMING OF DISCRETE NANOMATERIALS FOR SENSORS, TEMPLATES AND MIMICS OF NATURAL NANOSCALE ASSEMBLIES...Performance 3. DATES COVERED (From - To) 01 Jun 2011 to 31 May 2016 4. TITLE AND SUBTITLE BIOMOLECULAR PROGRAMMING OF DISCRETE NANOMATERIALS FOR SENSORS...responsive elements for assembly of complex morphology switchable nanomaterials , and have combined this with an effort in nature-inspired materials

  14. An electronic nose for the detection of Sarin, Soman and Tabun mimics and interfering agents

    OpenAIRE

    2014-01-01

    An electronic nose system (E-nose) with metal oxide semiconductor sensors (MOS) has been designed to discriminate and quantify different chemical warfare agents (CWA) mimics. The E-nose consists of an array of commercial MOS for different gases, two sensors for temperature sensing, a sample handling system, a data acquisition system and a laptop with the data acquisition system control. With this device, discrimination studies have been carried out to detect specific CWA simulants...

  15. Contact hypersensitivity to mercury in amalgam restorations may mimic oral lichen planus.

    Science.gov (United States)

    Camisa, C; Taylor, J S; Bernat, J R; Helm, T N

    1999-03-01

    Oral lichenoid lesions caused by hypersensitivity to mercury in amalgam fillings may mimic oral lichen planus on clinical and histologic examination. A positive patch test reaction to more than one mercurial allergen increases confidence in the diagnosis and justifies the removal and replacement of all amalgam fillings with those made of other materials. A complete remission may be expected about 3 months after the last amalgam filling is removed.

  16. Evidence that Cerambycid Beetles Mimic Vespid Wasps in Odor as well as Appearance.

    Science.gov (United States)

    Mitchell, Robert F; Curkovic, Tomislav; Mongold-Diers, Judith A; Neuteboom, Lara; Galbrecht, Hans-Martin; Tröger, Armin; Bergmann, Jan; Francke, Wittko; Hanks, Lawrence M

    2017-01-01

    We present evidence that cerambycid species that are supposed mimics of vespid wasps also mimic their model's odor by producing spiroacetals, common constituents of vespid alarm pheromones. Adults of the North American cerambycids Megacyllene caryae (Gahan) and Megacyllene robiniae (Forster) are conspicuously patterned yellow and black, and are believed to be mimics of aculeate Hymenoptera, such as species of Vespula and Polistes. Adult males of M. caryae produce an aggregation-sex pheromone, but both sexes produce a pungent odor when handled, which has been assumed to be a defensive response. Headspace aerations of agitated females of M. caryae contained 16 compounds with mass spectra characteristic of spiroacetals of eight distinct chemical structures, with the dominant compound being (7E,2E)-7-ethyl-2-methyl-1,6-dioxaspiro[4.5]decane. Headspace samples of agitated males of M. caryae contained five of the same components, with the same dominant compound. Females of M. robiniae produced six different spiroacetals, one of which was not produced by M. caryae, (2E,7E)-2-ethyl-7-methyl-1,6-dioxaspiro[4.5]decane, and five that were shared with M. caryae, including the dominant (2E,8E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane. The latter compound is the sole spiroacetal produced by both males and females of a South American cerambycid species, Callisphyris apicicornis (Fairmaire & Germain), which is also thought to be a wasp mimic. Preliminary work also identified spiroacetals of similar or identical structure released by vespid wasps that co-occur with the Megacyllene species.

  17. Representing life in the Earth system with soil microbial functional traits in the MIMICS model

    Science.gov (United States)

    Wieder, W. R.; Grandy, A. S.; Kallenbach, C. M.; Taylor, P. G.; Bonan, G. B.

    2015-06-01

    Projecting biogeochemical responses to global environmental change requires multi-scaled perspectives that consider organismal diversity, ecosystem processes, and global fluxes. However, microbes, the drivers of soil organic matter decomposition and stabilization, remain notably absent from models used to project carbon (C) cycle-climate feedbacks. We used a microbial trait-based soil C model with two physiologically distinct microbial communities, and evaluate how this model represents soil C storage and response to perturbations. Drawing from the application of functional traits used to model other ecosystems, we incorporate copiotrophic and oligotrophic microbial functional groups in the MIcrobial-MIneral Carbon Stabilization (MIMICS) model; these functional groups are akin to "gleaner" vs. "opportunist" plankton in the ocean, or r- vs. K-strategists in plant and animal communities. Here we compare MIMICS to a conventional soil C model, DAYCENT (the daily time-step version of the CENTURY model), in cross-site comparisons of nitrogen (N) enrichment effects on soil C dynamics. MIMICS more accurately simulates C responses to N enrichment; moreover, it raises important hypotheses involving the roles of substrate availability, community-level enzyme induction, and microbial physiological responses in explaining various soil biogeochemical responses to N enrichment. In global-scale analyses, we show that MIMICS projects much slower rates of soil C accumulation than a conventional soil biogeochemistry in response to increasing C inputs with elevated carbon dioxide (CO2) - a finding that would reduce the size of the land C sink estimated by the Earth system. Our findings illustrate that tradeoffs between theory and utility can be overcome to develop soil biogeochemistry models that evaluate and advance our theoretical understanding of microbial dynamics and soil biogeochemical responses to environmental change.

  18. Some tropical viral diseases that can mimic swine flu in pediatrics

    OpenAIRE

    Wiwanitkit, Viroj

    2009-01-01

    Abstract Swine flu is an important emerging infection that is presently pandemic around the world. The pediatric population is an important group that can be infected with swine flu. Generally, common presentations of swine flu include fever and respiratory presentations. However, there are several infections that can have similar presentations to swine flu. In this specific article, the author will briefly discuss on some tropical viral diseases that can mimic swine flu in pediatrics. ...

  19. Some tropical viral diseases that can mimic swine flu in pediatrics

    Directory of Open Access Journals (Sweden)

    Viroj WIWANITKIT

    2009-11-01

    Full Text Available Swine flu is an important emerging infection that is presently pandemic around the world. The pediatric population is an important group that can be infected with swine flu. Generally, common presentations of swine flu include fever and respiratory presentations. However, there are several infections that can have similar presentations to swine flu. In this specific article, the author will briefly discuss on some tropical viral diseases that can mimic swine flu in pediatrics.

  20. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

    Institute of Scientific and Technical Information of China (English)

    Jia Fang; Ming-Sheng Liu; Yu-Zhou Guan; Hua Du; Ben-Hong Li; Bo Cui; Qing-Yun Ding

    2016-01-01

    Background:Amyotrophic lateral sclerosis (ALS) and some mimic disorders,such as distal-type cervical spondylotic amyotrophy (CSA),Hirayama disease (HD),and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy.This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders.Methods:We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients,95 patients with distal-type CSA,88 HD patients,43 SBMA patients,and 150 normal controls.Results:The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P < 0.001) than that in the normal controls.The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA (P < 0.001) and the HD patients (P < 0.001) compared with that in the normal controls.The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients (P =0.004).The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients (P < 0.001) than that in the patients with distal-type CSA.The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls (P =0.862).An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (>4.5) were observed exclusively in the ALS patients.Conclusions:The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders,and may aid in distinguishing between ALS and mimic disorders.

  1. Manganese Superoxide Dismutase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cencer Patients Treated with Cyclophosphamide Epirubicin and 5-Fluororacil

    DEFF Research Database (Denmark)

    Ording, Anne Gulbech; Cronin Fenton, Deirdre; Christensen, Mariann

    2012-01-01

    Manganese Superoxide Dismutase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cencer Patients Treated with Cyclophosphamide Epirubicin and 5-Fluororacil......Manganese Superoxide Dismutase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cencer Patients Treated with Cyclophosphamide Epirubicin and 5-Fluororacil...

  2. The cytoplasmic Cu,Zn superoxide dismutase of saccharomyces cerevisiae is required for resistance to freeze-thaw stress. Generation of free radicals during freezing and thawing

    DEFF Research Database (Denmark)

    Park, J I; Grant, C M; Davies, Michael Jonathan

    1998-01-01

    The involvement of oxidative stress in freeze-thaw injury to yeast cells was analyzed using mutants defective in a range of antioxidant functions, including Cu,Zn superoxide dismutase (encoded by SOD1), Mn superoxide dismutase (SOD2), catalase A, catalase T, glutathione reductase, gamma-glutamylc...

  3. Settlement pattern of Posidonia oceanica epibionts along a gradient of ocean acidification: an approach with mimics

    Directory of Open Access Journals (Sweden)

    L. DONNARUMMA

    2014-02-01

    Full Text Available Effects of ocean acidification (OA on the colonization/settlement pattern of the epibiont community of the leaves and rhizomesof the Mediterranean seagrass,Posidoniaoceanica, have been studied at volcanic CO2vents off Ischia (Italy, using “mimics”as artificial substrates. The experiments were conducted in shallowPosidoniastands (2-3 m depth, in three stations on the northand three on the south sides of the study area, distributed along a pH gradient. At each station, 4 rhizome mimics and 6 artificialleaves were collected every three months (Sept 2009-Sept 2010. The epibionts on both leaf and rhizome mimics showed clearchanges along the pH gradient; coralline algae and calcareous invertebrates (bryozoans, serpulid polychaetes and barnacles weredominant at control stations but progressively disappeared at the most acidified stations. In these extremely low pH sites theassemblage was dominated by filamentous algae and non calcareous taxa such as hydroids and tunicates. Settlement pattern onthe artificial leaves and rhizome mimics over time showed a consistent distribution pattern along the pH gradient and highlightedthe peak of recruitment of the various organisms in different periods according to their life history.Posidoniamimics at theacidified station showed a poor and very simplified assemblage where calcifying epibionts seemed less competitive for space. Thisprofound difference in epiphyte communities in low pH conditions suggests cascading effects on the food web of the meadow and,consequently, on the functioning of the system

  4. Settlement pattern of Posidonia oceanica epibionts along a gradient of ocean acidification: an approach with mimics

    Directory of Open Access Journals (Sweden)

    L. DONNARUMMA

    2014-09-01

    Full Text Available Effects of ocean acidification (OA on the colonization/settlement pattern of the epibiont community of the leaves and rhizomesof the Mediterranean seagrass,Posidoniaoceanica, have been studied at volcanic CO2vents off Ischia (Italy, using “mimics”as artificial substrates. The experiments were conducted in shallowPosidoniastands (2-3 m depth, in three stations on the northand three on the south sides of the study area, distributed along a pH gradient. At each station, 4 rhizome mimics and 6 artificialleaves were collected every three months (Sept 2009-Sept 2010. The epibionts on both leaf and rhizome mimics showed clearchanges along the pH gradient; coralline algae and calcareous invertebrates (bryozoans, serpulid polychaetes and barnacles weredominant at control stations but progressively disappeared at the most acidified stations. In these extremely low pH sites theassemblage was dominated by filamentous algae and non calcareous taxa such as hydroids and tunicates. Settlement pattern onthe artificial leaves and rhizome mimics over time showed a consistent distribution pattern along the pH gradient and highlightedthe peak of recruitment of the various organisms in different periods according to their life history.Posidoniamimics at theacidified station showed a poor and very simplified assemblage where calcifying epibionts seemed less competitive for space. Thisprofound difference in epiphyte communities in low pH conditions suggests cascading effects on the food web of the meadow and,consequently, on the functioning of the system

  5. Pd-Ir Core-Shell Nanocubes: A Type of Highly Efficient and Versatile Peroxidase Mimic.

    Science.gov (United States)

    Xia, Xiaohu; Zhang, Jingtuo; Lu, Ning; Kim, Moon J; Ghale, Kushal; Xu, Ye; McKenzie, Erin; Liu, Jiabin; Ye, Haihang

    2015-10-27

    Peroxidase mimics with dimensions on the nanoscale have received great interest as emerging artificial enzymes for biomedicine and environmental protection. While a variety of peroxidase mimics have been actively developed recently, limited progress has been made toward improving their catalytic efficiency. In this study, we report a type of highly efficient peroxidase mimic that was engineered by depositing Ir atoms as ultrathin skins (a few atomic layers) on Pd nanocubes (i.e., Pd-Ir cubes). The Pd-Ir cubes exhibited significantly enhanced efficiency, with catalytic constants more than 20- and 400-fold higher than those of the initial Pd cubes and horseradish peroxidase (HRP), respectively. As a proof-of-concept demonstration, the Pd-Ir cubes were applied to the colorimetric enzyme-linked immunosorbent assay (ELISA) of human prostate surface antigen (PSA) with a detection limit of 0.67 pg/mL, which is ∼110-fold lower than that of the conventional HRP-based ELISA using the same set of antibodies and the same procedure.

  6. Tunable Molecular MoS2 Edge-Site Mimics for Catalytic Hydrogen Production.

    Science.gov (United States)

    Garrett, Benjamin R; Polen, Shane M; Click, Kevin A; He, Mingfu; Huang, Zhongjie; Hadad, Christopher M; Wu, Yiying

    2016-04-18

    Molybdenum sulfides represent state-of-the-art, non-platinum electrocatalysts for the hydrogen evolution reaction (HER). According to the Sabatier principle, the hydrogen binding strength to the edge active sites should be neither too strong nor too weak. Therefore, it is of interest to develop a molecular motif that mimics the catalytic sites structurally and possesses tunable electronic properties that influence the hydrogen binding strength. Furthermore, molecular mimics will be important for providing mechanistic insight toward the HER with molybdenum sulfide catalysts. In this work, a modular method to tune the catalytic properties of the S-S bond in MoO(S2)2L2 complexes is described. We studied the homogeneous electrocatalytic hydrogen production performance metrics of three catalysts with different bipyridine substitutions. By varying the electron-donating abilities, we present the first demonstration of using the ligand to tune the catalytic properties of the S-S bond in molecular MoS2 edge-site mimics. This work can shed light on the relationship between the structure and electrocatalytic activity of molecular MoS2 catalysts and thus is of broad importance from catalytic hydrogen production to biological enzyme functions.

  7. Antibacterial TAP-mimic Electrospun Polymer Scaffold – Effects on P. gingivalis-Infected Dentin Biofilm

    Science.gov (United States)

    Albuquerque, Maria Tereza P.; Evans, Joshua D.; Gregory, Richard L.; Valera, Marcia C.; Bottino, Marco C.

    2016-01-01

    Objectives This study sought to investigate, in-vitro, the effects of a recently developed triple antibiotic paste (TAP)-mimic polymer nanofibrous scaffold against Porphyromonas gingivalis (Pg)-infected dentin biofilm. Materials and Methods Dentin specimens (4×4×1mm3) were prepared from human canines. The specimens were sterilized, inoculated with Pg (ATCC 33277), and incubated for one week to allow for biofilm formation. Infected dentin specimens were exposed for 3 days to the following treatments: antibiotic-free polydioxanone scaffold (PDS, control), PDS+25wt.%TAP (25 mg of each antibiotic [metronidazole, ciprofloxacin, and minocycline] per mL of the PDS polymer solution), or a saturated TAP-based solution (50 mg of each antibiotic per mL of saline solution). In order to serve as the negative control, infected dentin specimens were left untreated (bacteria only). To determine the antimicrobial efficacy of the TAP-mimic scaffold, a colony-forming unit (CFU/mL) (n=10/group) measurement was performed. Furthermore, additional specimens (n=2/group) were prepared to qualitatively study biofilm inhibition via scanning electron microscopy (SEM). Statistics were performed and significance was set at the 5% level. Results Both the TAP-mimic scaffold and the positive control (TAP solution) led to complete bacterial elimination, differing statistically (pregenerative endodontics. PMID:26319981

  8. MiRNA mimic screen for improved expression of functional neurotensin receptor from HEK293 cells.

    Science.gov (United States)

    Xiao, Su; Chen, Yu-Chi; Betenbaugh, Michael J; Martin, Scott E; Shiloach, Joseph

    2015-08-01

    Obtaining adequate quantities of functional mammalian membrane proteins has been a bottleneck in their structural and functional studies because the expression of these proteins from mammalian cells is relatively low. To explore the possibility of enhancing expression of these proteins using miRNA, a stable T-REx-293 cell line expressing the neurotensin receptor type 1 (NTSR1), a hard-to-express G protein-coupled receptor (GPCR), was constructed. The cell line was then subjected to human miRNA mimic library screening. In parallel, an HEK293 cell line expressing luciferase was also screened with the same human miRNA mimic library. Five microRNA mimics: hsa-miR-22-5p, hsa-miR-18a-5p, hsa-miR-22-3p, hsa-miR-429, and hsa-miR-2110were identified from both screens. They led to 48% increase in the expression of functional NTSR1 and to 239% increase of luciferase expression. These miRNAs were also effective in enhancing the expression of secretedglypican-3 hFc-fusion protein from HEK293 cells.The results indicate that these molecules may have a wide role in enhancing the production of proteins with biomedical interest.

  9. Gibberellic and kaurenoic hybrid strigolactone mimics for seed germination of parasitic weeds.

    Science.gov (United States)

    Pereira, Rondinelle G; Cala, Antonio; Fernández-Aparicio, Mónica; Molinillo, José Mg; Boaventura, Maria Ad; Macías, Francisco A

    2017-06-23

    Parasitic weeds are widespread and cause significant losses in important crops. Their germination requires the detection of crop-derived molecules such as strigolactones. Strigolactone mimics are germination-inducing molecules with the potential to apply a suicidal germination strategy for seed bank control of parasitic weeds. The D-ring, which is instrumental in the germination process of seeds of parasitic weeds, was attached to gibberellin (GA3 ) and kaurenoic acid as the scaffold. It was shown that indeed strigolactone mimics prepared from GA3 and kaurenoic acid are active as stimulants when a D-ring is present; some of the mimics are as active as GR24. The starting molecules were plant hormones that had previous growth-regulating activity in other organisms and the products showed enhanced activity towards parasitic weeds. The information generated may contribute to a better understanding of the germination biochemistry of the weed species used. Further research is required in this area but it is clear that the results are promising. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  10. A collection of target mimics for comprehensive analysis of microRNA function in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Marco Todesco

    2010-07-01

    Full Text Available Many targets of plant microRNAs (miRNAs are thought to play important roles in plant physiology and development. However, because plant miRNAs are typically encoded by medium-size gene families, it has often been difficult to assess their precise function. We report the generation of a large-scale collection of knockdowns for Arabidopsis thaliana miRNA families; this has been achieved using artificial miRNA target mimics, a recently developed technique fashioned on an endogenous mechanism of miRNA regulation. Morphological defects in the aerial part were observed for approximately 20% of analyzed families, all of which are deeply conserved in land plants. In addition, we find that non-cleavable mimic sites can confer translational regulation in cis. Phenotypes of plants expressing target mimics directed against miRNAs involved in development were in several cases consistent with previous reports on plants expressing miRNA-resistant forms of individual target genes, indicating that a limited number of targets mediates most effects of these miRNAs. That less conserved miRNAs rarely had obvious effects on plant morphology suggests that most of them do not affect fundamental aspects of development. In addition to insight into modes of miRNA action, this study provides an important resource for the study of miRNA function in plants.

  11. Virulent Burkholderia species mimic host actin polymerases to drive actin-based motility

    Science.gov (United States)

    Benanti, Erin L.; Nguyen, Catherine M.; Welch, Matthew D.

    2015-01-01

    Summary Burkholderia pseudomallei and B. mallei are bacterial pathogens that cause melioidosis and glanders, while their close relative B. thailandensis is nonpathogenic. All use the trimeric autotransporter BimA to facilitate actin-based motility, host cell fusion and dissemination. Here, we show that BimA orthologs mimic different host actin-polymerizing proteins. B. thailandensis BimA activates the host Arp2/3 complex. In contrast, B. pseudomallei and B. mallei BimA mimic host Ena/VASP actin polymerases in their ability to nucleate, elongate and bundle filaments by associating with barbed ends, as well as in their use of WH2 motifs and oligomerization for activity. Mechanistic differences among BimA orthologs resulted in distinct actin filament organization and motility parameters, which affected the efficiency of cell fusion during infection. Our results identify bacterial Ena/VASP mimics and reveal that pathogens imitate the full spectrum of host actin-polymerizing pathways, suggesting that mimicry of different polymerization mechanisms influences key parameters of infection. PMID:25860613

  12. A search for symbiotic behaviour amongst OH/IR colour mimics

    CERN Document Server

    Seaquist, E R

    1994-01-01

    Recent maser surveys have shown that many potential OH/IR stars have no OH masers in their circumstellar envelopes, despite the modest requirements which should be implicitly met by IRAS colour-selected candidates. It has been suggested that these OH/IR colour mimics must have a degenerate companion which dissociates OH molecules and disrupts the masing action, ie. that they are related to symbiotic Miras. Coincidentally, there is a paucity of long-period symbiotic Miras and symbiotic OH/IR stars. Phenomonologically, those that are known seem to cluster in the zone where field Miras transform into OH/IR stars. If it could be proven that OH/IR colour mimics contain a degenerate star, that observable evidence of this star is hidden from view by CS dust whilst it slowly accretes from the wind of its Mira companion, then we have an excellent explanation for not only the existence of OH/IR colour mimics, but also for the low observed frequency of symbiotic OH/IR stars and the common occurrence of very slow novae i...

  13. Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In Compacted Nucleosome Arrays

    Science.gov (United States)

    Mishra, Laxmi N.; Pepenella, Sharon; Rogge, Ryan; Hansen, Jeffrey C.; Hayes, Jeffrey J.

    2016-01-01

    The activation of a silent gene locus is thought to involve pioneering transcription factors that initiate changes in the local chromatin structure to increase promoter accessibility and binding of downstream effectors. To better understand the molecular requirements for the first steps of locus activation, we investigated whether acetylation of a single nucleosome is sufficient to alter DNA accessibility within a condensed 25-nucleosome array. We found that acetylation mimics within the histone H4 tail domain increased accessibility of the surrounding linker DNA, with the increased accessibility localized to the immediate vicinity of the modified nucleosome. In contrast, acetylation mimics within the H3 tail had little effect, but were able to synergize with H4 tail acetylation mimics to further increase accessibility. Moreover, replacement of the central nucleosome with a nucleosome free region also resulted in increased local, but not global DNA accessibility. Our results indicate that modification or disruption of only a single target nucleosome results in significant changes in local chromatin architecture and suggest that very localized chromatin modifications imparted by pioneer transcription factors are sufficient to initiate a cascade of events leading to promoter activation. PMID:27708426

  14. MIMIC: An Innovative Methodology for Determining Mobile Laser Scanning System Point Density

    Directory of Open Access Journals (Sweden)

    Conor Cahalane

    2014-08-01

    Full Text Available Understanding how various Mobile Mapping System (MMS laser hardware configurations and operating parameters exercise different influence on point density is important for assessing system performance, which in turn facilitates system design and MMS benchmarking. Point density also influences data processing, as objects that can be recognised using automated algorithms generally require a minimum point density. Although obtaining the necessary point density impacts on hardware costs, survey time and data storage requirements, a method for accurately and rapidly assessing MMS performance is lacking for generic MMSs. We have developed a method for quantifying point clouds collected by an MMS with respect to known objects at specified distances using 3D surface normals, 2D geometric formulae and line drawing algorithms. These algorithms were combined in a system called the Mobile Mapping Point Density Calculator (MIMIC and were validated using point clouds captured by both a single scanner and a dual scanner MMS. Results from MIMIC were promising: when considering the number of scan profiles striking the target, the average error equated to less than 1 point per scan profile. These tests highlight that MIMIC is capable of accurately calculating point density for both single and dual scanner MMSs.

  15. Cloning, Expression and Characterization of Mitochondrial Manganese Superoxide Dismutase from the Whitefly, Bemisia tabaci

    Directory of Open Access Journals (Sweden)

    Xian-Long Gao

    2013-01-01

    Full Text Available A mitochondrial manganese superoxide dismutase from an invasive species of the whitefly Bemisia tabaci complex (Bt-mMnSOD was cloned and analyzed. The full length cDNA of Bt-mMnSOD is 1210 bp with a 675 bp open reading frame, corresponding to 224 amino acids, which include 25 residues of the mitochondrial targeting sequence. Compared with various vertebrate and invertebrate animals, the MnSOD signature (DVWEHAYY and four conserved amino acids for manganese binding (H54, H102, D186 and H190 were observed in Bt-mMnSOD. Recombinant Bt-mMnSOD was overexpressed in Escherichia coli, and the enzymatic activity of purified mMnSOD was assayed under various temperatures. Quantitative real-time PCR analysis with whiteflies of different development stages showed that the mRNA levels of Bt-mMnSOD were significantly higher in the 4th instar than in other stages. In addition, the in vivo activities of MnSOD in the whitefly were measured under various conditions, including exposure to low (4 °C and high (40 °C temperatures, transfer from a favorable to an unfavorable host plant (from cotton to tobacco and treatment with pesticides. Our results indicate that the whitefly MnSOD plays an important role in cellular stress responses and anti-oxidative processes and that it might contribute to the successful worldwide distribution of the invasive whitefly.

  16. Folding of Cu, Zn superoxide dismutase and Familial Amyotrophic Lateral Sclerosis

    CERN Document Server

    Khare, S D; Dokholyan, N V; Khare, Sagar D.; Ding, Feng; Dokholyan, Nikolay V.

    2003-01-01

    Cu,Zn superoxide dismutase (SOD1) has been implicated in the familial form of the neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). It has been suggested that mutant mediated SOD1 misfolding/aggregation is an integral part of the pathology of ALS. We study the folding thermodynamics and kinetics of SOD1 using a hybrid molecular dynamics approach. We reproduce the experimentally observed SOD1 folding thermodynamics and find that the residues which contribute the most to SOD1 thermal stability are also crucial for apparent two-state folding kinetics. Surprisingly, we find that these residues are located on the surface of the protein and not in the hydrophobic core. Mutations in some of the identified residues are found in patients with the disease. We argue that the identified residues may play an important role in aggregation. To further characterize the folding of SOD1, we study the role of cysteine residues in folding and find that non-native disulfide bond formation may significantly alter SOD1...

  17. Structural basis of heme binding in the Cu,Zn superoxide dismutase from Haemophilus ducreyi.

    Science.gov (United States)

    Töro, Imre; Petrutz, Cristiana; Pacello, Francesca; D'Orazio, Melania; Battistoni, Andrea; Djinović-Carugo, Kristina

    2009-02-20

    The Cu,Zn superoxide dismutase from Haemophilus ducreyi is characterized by the unique ability to bind heme at its dimer interface. Here we report the high-resolution crystal structures of this protein in the heme-loaded (holo) and heme-free (apo) forms. Heme is asymmetrically bound between the two enzyme subunits, where heme iron is coordinated by two histidine residues, His64 and His 124, provided by the two subunits. Moreover, the binding of heme to the protein is ensured by stabilizing contacts between the prosthetic group and a limited number of other residues, most of which are not present in other bacterial enzyme variants. We show that the introduction of only three mutations at the dimer interface of the enzyme from Haemophilus parainfluenzae, a closely related bacterial species, is sufficient to induce heme-binding ability by this enzyme variant. Heme binding does not alter protein activity. Moreover, the binding of the prosthetic group does not induce any significant structural perturbation at the subunit level and requires only limited local structural rearrangements that widen the cleft at the dimer interface and cause a limited shift in the relative orientation between the subunits. The presence of a preformed heme-binding pocket and the significant solvent exposure of the cofactor to the solvent are compatible with the suggested protective role of the enzyme against heme toxicity or with its involvement in heme trafficking in the periplasmic space.

  18. Searching for convergent evolution in manganese superoxidase dismutase using hydrophobic cluster analysis

    Directory of Open Access Journals (Sweden)

    Heng Xiang

    2014-06-01

    Full Text Available There are numerous examples of convergent evolution in nature. Major ecological adaptations such as flight, loss of limbs in vertebrates, pesticide resistance, adaptation to a parasitic way of life, etc., have all evolved more than once, as seen by their analogous functions in separate taxa. But what about protein evolution? Does the environment have a strong enough influence on intracellular processes that enzymes and other functional proteins play, to evolve similar functional roles separately in different organisms? Manganese Superoxide Dismutase (MnSOD is a manganesedependant metallo-enzyme which plays a crucial role in protecting cells from anti-oxidative stress by eliminating reactive (superoxide oxygen species. It is a ubiquitous housekeeping enzyme found in nearly all organisms. In this study we compare phylogenies based on MnSOD protein sequences to those based on scores from Hydrophobic Cluster Analysis (HCA. We calculated HCA similarity values for each pair of taxa to obtain a pair-wise distance matrix. A UPGMA tree based on the HCA distance matrix and a common tree based on the primary protein sequence for MnSOD was constructed. Differences between these two trees within animals, enterobacteriaceae, planctomycetes and cyanobacteria are presented and cited as possible examples of convergence. We note that several residue changes result in changes in hydrophobicity at positions which apparently are under the effect of positive selection.

  19. Paradoxical relationship between Mn superoxide dismutase deficiency and radiation-induced cognitive defects.

    Directory of Open Access Journals (Sweden)

    Rikki Corniola

    Full Text Available Radiation therapy of the CNS, even at low doses, can lead to deficits in neurocognitive functions. Reduction in hippocampal neurogenesis is usually, but not always, associated with cognitive deficits resulting from radiation therapy. Generation of reactive oxygen species is considered the main cause of radiation-induced tissue injuries, and elevated levels of oxidative stress persist long after the initial cranial irradiation. Consequently, mutant mice with reduced levels of the mitochondrial antioxidant enzyme, Mn superoxide dismutase (MnSOD or Sod2, are expected to be more sensitive to radiation-induced changes in hippocampal neurogenesis and the related functions. In this study, we showed that MnSOD deficiency led to reduced generation of immature neurons in Sod2-/+ mice even though progenitor cell proliferation was not affected. Compared to irradiated Sod2+/+ mice, which showed cognitive defects and reduced differentiation of newborn cells towards the neuronal lineage, irradiated Sod2-/+ mice showed normal hippocampal-dependent cognitive functions and normal differentiation pattern for newborn neurons and astroglia. However, we also observed a disproportional decrease in newborn neurons in irradiated Sod2-/+ following behavioral studies, suggesting that MnSOD deficiency may render newborn neurons more sensitive to stress from behavioral trainings following cranial irradiation. A positive correlation between normal cognitive functions and normal dendritic spine densities in dentate granule cells was observed. The data suggest that maintenance of synaptic connections, via maintenance of dendritic spines, may be important for normal cognitive functions following cranial irradiation.

  20. Pathological Roles of Wild-Type Cu, Zn-Superoxide Dismutase in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Yoshiaki Furukawa

    2012-01-01

    Full Text Available Dominant mutations in a Cu, Zn-superoxide dismutase (SOD1 gene cause a familial form of amyotrophic lateral sclerosis (ALS. While it remains controversial how SOD1 mutations lead to onset and progression of the disease, many in vitro and in vivo studies have supported a gain-of-toxicity mechanism where pathogenic mutations contribute to destabilizing a native structure of SOD1 and thus facilitate misfolding and aggregation. Indeed, abnormal accumulation of SOD1-positive inclusions in spinal motor neurons is a pathological hallmark in SOD1-related familial ALS. Furthermore, similarities in clinical phenotypes and neuropathology of ALS cases with and without mutations in sod1 gene have implied a disease mechanism involving SOD1 common to all ALS cases. Although pathogenic roles of wild-type SOD1 in sporadic ALS remain controversial, recent developments of novel SOD1 antibodies have made it possible to characterize wild-type SOD1 under pathological conditions of ALS. Here, I have briefly reviewed recent progress on biochemical and immunohistochemical characterization of wild-type SOD1 in sporadic ALS cases and discussed possible involvement of wild-type SOD1 in a pathomechanism of ALS.

  1. Scavenging of superoxide anions by lecithinized superoxide dismutase in HL-60 cells.

    Science.gov (United States)

    Ishihara, Tsutomu; Shibui, Misaki; Hoshi, Takaya; Mizushima, Tohru

    2016-01-01

    Superoxide dismutase covalently bound to four lecithin molecules (PC-SOD) has been found to have beneficial therapeutic effects in animal models of various diseases. However, the mechanism underlying these improved therapeutic effects has not yet been elucidated. It has previously been shown that PC-SOD localizes on the plasma membrane and in the lysosomes of cells. In this study, we evaluated the superoxide anion-scavenging activity of PC-SOD in HL-60 human promyelocytic leukemia cells. Compared to SOD, PC-SOD had only 17% scavenging activity in cell-free systems. Nevertheless, by analyzing enzyme activities in cell suspensions containing PC-SOD or SOD, PC-SOD and SOD showed almost equal activity for scavenging extracellular superoxide anions produced by HL-60 cells. Furthermore, the activity for scavenging extracellular superoxide anions increased with increased amount of PC-SOD on the plasma membrane. Moreover, PC-SOD exhibited no obvious inhibitory effect on the scavenging of intracellular superoxide anions. These results suggested that the association of PC-SOD with the plasma membrane plays a key role in its beneficial therapeutic effects. Thus, this finding may provide a rationale for selecting target diseases for PC-SOD treatment.

  2. Mitochondrial superoxide dismutase deficiency accelerates chronological aging in the fission yeast Schizosaccharomyces pombe.

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    Ogata, Toshiya; Senoo, Takanori; Kawano, Shinji; Ikeda, Shogo

    2016-01-01

    A mitochondrial superoxide dismutase (SOD2) is the first line of antioxidant defense against mitochondrial superoxide. Even though the involvement of SOD2 in lifespan has been studied extensively in several organisms, characterization of the aging process has not been performed for the sod2 mutant (sod2Δ) of a prominent model Schizosaccharomyces pombe. In this study, we measured the chronological lifespan of sod2Δ cells by their ability to survive in long-term culture. SOD2 deficiency drastically decreased cell viability in the stationary phase. The mutation frequency of nuclear DNA in sod2Δ was elevated in the stationary phase, and cellular proteins and nuclear DNA were extensively degraded, concurrent with cell death. The sod2 gene in wild-type cells could be induced by an increase in endogenous oxidative stresses, after which, SOD2 activity was substantially elevated during the stationary phase. Culture in a lower glucose concentration (calorie restriction) prominently extended the sod2Δ lifespan. Therefore, S. pombe SOD2 plays a critical role in longevity through its upregulation in the non-dividing phase.

  3. A seeded propagation of Cu,Zn-superoxide dismutase aggregates in amyotrophic lateral sclerosis

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    Mariko eOgawa

    2014-03-01

    Full Text Available Abnormal accumulation of protein inclusions in motor neurons has been known as a major pathological change in amyotrophic lateral sclerosis (ALS. Increasing numbers of proteins including mutant Cu,Zn-superoxide dismutase (SOD1 have been identified as constituents of pathological inclusions in a form of insoluble fibrillar aggregates. Notably, protein fibrillar aggregates exhibit a self-perpetuating property, which can convert a soluble native protein into insoluble fibrillar aggregates. Such seeding reaction of protein fibrils can accelerate the aggregation significantly and would contribute to the spread of inclusion pathologies from an affected cell to its neighboring cells in neurodegenerative diseases. In ALS, a pathological change first occurs at the site of disease onset and then propagates throughout the affected tissues in a time-dependent manner; therefore, it can be assumed that seeded aggregation may be the key factor of disease progression in ALS. In this mini review, we will briefly summarize recent studies on possible roles of a seeded aggregation of SOD1 in pathomechanism of ALS.

  4. Gain of interaction of ALS-linked G93A superoxide dismutase with cytosolic malate dehydrogenase.

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    Mali, Yael; Zisapels, Nava

    2008-10-01

    Protein interactions of the Amyotrophic Lateral Sclerosis (ALS)-linked copper-zinc superoxide dismutase (hSOD1) G93A mutation were studied using a fluorescence resonance energy transfer (FRET) based screening system. The FRET results confirmed by pull-down immunoprecipitation indicated "gain-of-interaction" of the G93A-hSOD1 mutant with cytosolic malate dehydrogenase (cytMDH)-a key enzyme in the malate-aspartate shuttle which is vital to neurons. Furthermore, cytMDH mRNA expression was upregulated in G93A-hSOD1 expressing cells but endogenous cytMDH enzymatic activity was not enhanced, not even with exogenously added-on enzyme. Consistent with inhibition of the malate-aspartate shuttle, G93A-hSOD1 had lower malate and higher lactate levels compared to non-induced or Wild-Type-hSOD1 expressing cells. Mitochondrial NADH/NAD+ ratio is also elevated. Malate-aspartate shuttle dysfunction may explain the damage to neurons and the vulnerability to impairments of glycolytic pathways in ALS and provide a new target for the development of potential therapies.

  5. Cytotoxicity of superoxide dismutase 1 in cultured cells is linked to Zn2+ chelation.

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    Ann-Sofi Johansson

    Full Text Available Neurodegeneration in protein-misfolding disease is generally assigned to toxic function of small, soluble protein aggregates. Largely, these assignments are based on observations of cultured neural cells where the suspect protein material is titrated directly into the growth medium. In the present study, we use this approach to shed light on the cytotoxic action of the metalloenzyme Cu/Zn superoxide dismutase 1 (SOD1, associated with misfolding and aggregation in amyotrophic lateral sclerosis (ALS. The results show, somewhat unexpectedly, that the toxic species of SOD1 in this type of experimental setting is not an aggregate, as typically observed for proteins implicated in other neuro-degenerative diseases, but the folded and fully soluble apo protein. Moreover, we demonstrate that the toxic action of apoSOD1 relies on the protein's ability to chelate Zn(2+ ions from the growth medium. The decreased cell viability that accompanies this extraction is presumably based on disturbed Zn(2+ homeostasis. Consistently, mutations that cause global unfolding of the apoSOD1 molecule or otherwise reduce its Zn(2+ affinity abolish completely the cytotoxic response. So does the addition of surplus Zn(2+. Taken together, these observations point at a case where the toxic response of cultured cells might not be related to human pathology but stems from the intrinsic limitations of a simplified cell model. There are several ways proteins can kill cultured neural cells but all of these need not to be relevant for neurodegenerative disease.

  6. Searching for convergent evolution in manganese superoxidase dismutase using hydrophobic cluster analysis.

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    Xiang, Heng; Zhang, Ruizhi; Li, Nengzhang; Vossbrinck, Charles R

    2014-06-01

    There are numerous examples of convergent evolution in nature. Major ecological adaptations such as flight, loss of limbs in vertebrates, pesticide resistance, adaptation to a parasitic way of life, etc., have all evolved more than once, as seen by their analogous functions in separate taxa. But what about protein evolution? Does the environment have a strong enough influence on intracellular processes that enzymes and other functional proteins play, to evolve similar functional roles separately in different organisms? Manganese Superoxide Dismutase (MnSOD) is a manganesedependant metallo-enzyme which plays a crucial role in protecting cells from anti-oxidative stress by eliminating reactive (superoxide) oxygen species. It is a ubiquitous housekeeping enzyme found in nearly all organisms. In this study we compare phylogenies based on MnSOD protein sequences to those based on scores from Hydrophobic Cluster Analysis (HCA). We calculated HCA similarity values for each pair of taxa to obtain a pair-wise distance matrix. A UPGMA tree based on the HCA distance matrix and a common tree based on the primary protein sequence for MnSOD was constructed. Differences between these two trees within animals, enterobacteriaceae, planctomycetes and cyanobacteria are presented and cited as possible examples of convergence. We note that several residue changes result in changes in hydrophobicity at positions which apparently are under the effect of positive selection.

  7. Superoxide Dismutase1 Levels in North Indian Population with Age-Related Macular Degeneration

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    Akshay Anand

    2013-01-01

    Full Text Available Aim. The aim of the study was to estimate the levels of superoxide dismutase1 (SOD1 in patients of age-related macular degeneration (AMD and examine the role of oxidative stress, smoking, hypertension, and other factors involved in the pathogenesis of AMD. Methods. 115 AMD patients and 61 healthy controls were recruited for this study. Serum SOD1 levels were determined by ELISA and were correlated to various risk factors. Logistic regression model of authenticity, by considering SOD1 as independent variable, has been developed along with ROC curve. Results. The SOD1 levels were significantly higher in AMD patients as compared to those of the controls. The difference was not significant for wet and dry AMD. However, the difference was significant between wet AMD subtypes. Nonsignificance of the Hosmer-Lemeshow goodness of fit statistic (χ2=10.516, df=8, P=0.231 indicates the appropriateness of logistic regression model to predict AMD. Conclusion. Oxidative stress in AMD patients may mount compensatory response resulting in increased levels of SOD1 in AMD patients. To predict the risk of AMD on the basis of SOD1, a logistic regression model shows authenticity of 78%, and area under the ROC curve (0.827, P=.0001 with less standard error of 0.033 coupled with 95% confidence interval of 0.762–0.891 further validates the model.

  8. Superoxide dismutase overexpression protects against glucocorticoid-induced depressive-like behavioral phenotypes in mice.

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    Uchihara, Yuki; Tanaka, Ken-ichiro; Asano, Teita; Tamura, Fumiya; Mizushima, Tohru

    2016-01-22

    In the stress response, activation of the hypothalamic-pituitary-adrenal axis, and particularly the release of glucocorticoids, plays a critical role. However, dysregulation of this system and sustained high plasma levels of glucocorticoids can result in depression. Recent studies have suggested the involvement of reactive oxygen species (ROS), such as superoxide anion, in depression. However, direct evidence for a role of ROS in the pathogenesis of this disorder is lacking. In this study, using transgenic mice expressing human Cu/Zn-superoxide dismutase (SOD1), an enzyme that catalyzes the dismutation of superoxide anions, we examined the effect of SOD1 overexpression on depressive-like behavioral phenotypes in mice. Depressive-like behaviors were induced by daily subcutaneous administration of the glucocorticoid corticosterone for 4 weeks, and was monitored with the social interaction test, the sucrose preference test and the forced swim test. These tests revealed that transgenic mice overexpressing SOD1 are more resistant to glucocorticoid-induced depressive-like behavioral disorders than wild-type animals. Furthermore, compared with wild-type mice, transgenic mice showed a reduction in the number of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress)-positive cells in the hippocampal CA3 region following corticosterone administration. These results suggest that overexpression of SOD1 protects mice against glucocorticoid-induced depressive-like behaviors by decreasing cellular ROS levels.

  9. Extracellular superoxide dismutase deficiency impairs wound healing in advanced age by reducing neovascularization and fibroblast function.

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    Fujiwara, Toshihiro; Duscher, Dominik; Rustad, Kristine C; Kosaraju, Revanth; Rodrigues, Melanie; Whittam, Alexander J; Januszyk, Michael; Maan, Zeshaan N; Gurtner, Geoffrey C

    2016-03-01

    Advanced age is characterized by impairments in wound healing, and evidence is accumulating that this may be due in part to a concomitant increase in oxidative stress. Extended exposure to reactive oxygen species (ROS) is thought to lead to cellular dysfunction and organismal death via the destructive oxidation of intra-cellular proteins, lipids and nucleic acids. Extracellular superoxide dismutase (ecSOD/SOD3) is a prime antioxidant enzyme in the extracellular space that eliminates ROS. Here, we demonstrate that reduced SOD3 levels contribute to healing impairments in aged mice. These impairments include delayed wound closure, reduced neovascularization, impaired fibroblast proliferation and increased neutrophil recruitment. We further establish that SOD3 KO and aged fibroblasts both display reduced production of TGF-β1, leading to decreased differentiation of fibroblasts into myofibroblasts. Taken together, these results suggest that wound healing impairments in ageing are associated with increased levels of ROS, decreased SOD3 expression and impaired extracellular oxidative stress regulation. Our results identify SOD3 as a possible target to correct age-related cellular dysfunction in wound healing.

  10. Superoxide dismutase and catalase activities in rat hippocampus pretreated with garcinielliptone FC from Platonia insignis.

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    da Costa Júnior, Joaquim S; de Almeida, Antonia Amanda C; Costa, Jéssica Pereira; das Graças Lopes Citó, Antonia Maria; Saffi, Jenifer; de Freitas, Rivelilson Mendes

    2012-04-01

    Platonia insignis Mart. (Clusiaceae), commonly known as "bacuri," is a timber and fruit native species of the Brazilian Amazon. Some plants of the Clusiaceae family have their pharmacological properties associated with the presence of xanthone and polycyclic polyprenylated acylphloroglucinols derivatives, which have antioxidant and anticarcinogenic activities. The aim of this study was to assess the in vivo potential of extracts, fractions, and garcinielliptone FC isolated from of Platonia insignis seeds as a natural antioxidant. Male Wistar rats (250-280 g; 2 months old) were treated with Tween 80 0.05% dissolved in 0.9% saline (i.p, vehicle - control group), ethanol extract (EE), hexane extract (HE), dichloromethane fraction (DMF), ethyl acetate fraction (EAF), and garcinielliptone FC (GFC) isolated from P. insignis at doses 2 mg/kg (i.p.). All groups were observed for 24 h after the treatment. The antioxidant enzymatic activities [superoxide dismutase (SOD) and catalase (CAT)] were measured using spectrophotometric methods. There were no marked alterations in SOD and CAT activities in rat hippocampus after pretreatment with EE, HE, DMF, EAF, and GFC. However, the pretreatment with GFC induced a significantly increase of 13, 17, 19, and 13% in SOD activities when compared to EE, HE, DMF, or EAF groups, respectively. Our findings strongly support the hypothesis that GFC isolated from P. insignis has a significant potential to be used as a natural antioxidant agent probably due to the modulation of enzymatic activity of hippocampal SOD.

  11. Genome-Wide Characterization and Expression Profiles of the Superoxide Dismutase Gene Family in Gossypium

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    Jingbo Zhang

    2016-01-01

    Full Text Available Superoxide dismutase (SOD as a group of significant and ubiquitous enzymes plays a critical function in plant growth and development. Previously this gene family has been investigated in Arabidopsis and rice; it has not yet been characterized in cotton. In our study, it was the first time for us to perform a genome-wide analysis of SOD gene family in cotton. Our results showed that 10 genes of SOD gene family were identified in Gossypium arboreum and Gossypium raimondii, including 6 Cu-Zn-SODs, 2 Fe-SODs, and 2 Mn-SODs. The chromosomal distribution analysis revealed that SOD genes are distributed across 7 chromosomes in Gossypium arboreum and 8 chromosomes in Gossypium raimondii. Segmental duplication is predominant duplication event and major contributor for expansion of SOD gene family. Gene structure and protein structure analysis showed that SOD genes have conserved exon/intron arrangement and motif composition. Microarray-based expression analysis revealed that SOD genes have important function in abiotic stress. Moreover, the tissue-specific expression profile reveals the functional divergence of SOD genes in different organs development of cotton. Taken together, this study has imparted new insights into the putative functions of SOD gene family in cotton. Findings of the present investigation could help in understanding the role of SOD gene family in various aspects of the life cycle of cotton.

  12. The role of two superoxide dismutase mRNAs in rye aluminium tolerance.

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    Sánchez-Parra, B; Figueiras, A M; Abd El-Moneim, D; Contreras, R; Rouco, R; Gallego, F J; Benito, C

    2015-05-01

    Aluminium (Al) is the main factor that limits crop production in acidic soils. There is evidence that antioxidant enzymes such as superoxide dismutase (SOD) play a key role against Al-induced oxidative stress in several plant species. Rye is one of the most Al-tolerant cereals and exudes both citrate and malate from the roots in response to Al. The role of SOD against Al-induced oxidative stress has not been studied in rye. Al accumulation, lipid peroxidation, H₂O₂ production and cell death were significantly higher in sensitive than in tolerant rye cultivars. Also, we characterised two genes for rye SOD: ScCu/ZnSOD and ScMnSOD. These genes were located on the chromosome arms of 2RS and 3RL, respectively, and their corresponding hypothetical proteins were putatively classified as cytosolic and mitochondrial, respectively. The phylogenetic relationships indicate that the two rye genes are orthologous to the corresponding genes of other Poaceae species. In addition, we studied Al-induced changes in the expression profiles of mRNAs from ScCu/ZnSOD and ScMnSOD in the roots and leaves of tolerant Petkus and sensitive Riodeva rye. These genes are mainly expressed in roots in both ryes, their repression being induced by Al. The tolerant cultivar has more of both mRNAs than the sensitive line, indicating that they are probably involved in Al tolerance.

  13. Differential inhibition of Arabidopsis superoxide dismutases by peroxynitrite-mediated tyrosine nitration.

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    Holzmeister, Christian; Gaupels, Frank; Geerlof, Arie; Sarioglu, Hakan; Sattler, Michael; Durner, Jörg; Lindermayr, Christian

    2015-02-01

    Despite the importance of superoxide dismutases (SODs) in the plant antioxidant defence system little is known about their regulation by post-translational modifications. Here, we investigated the in vitro effects of nitric oxide derivatives on the seven SOD isoforms of Arabidopsis thaliana. S-nitrosoglutathione, which causes S-nitrosylation of cysteine residues, did not influence SOD activities. By contrast, peroxynitrite inhibited the mitochondrial manganese SOD1 (MSD1), peroxisomal copper/zinc SOD3 (CSD3), and chloroplastic iron SOD3 (FSD3), but no other SODs. MSD1 was inhibited by up to 90% but CSD3 and FSD3 only by a maximum of 30%. Down-regulation of these SOD isoforms correlated with tyrosine (Tyr) nitration and both could be prevented by the peroxynitrite scavenger urate. Site-directed mutagenesis revealed that-amongst the 10 Tyr residues present in MSD1-Tyr63 was the main target responsible for nitration and inactivation of the enzyme. Tyr63 is located nearby the active centre at a distance of only 5.26 Å indicating that nitration could affect accessibility of the substrate binding pocket. The corresponding Tyr34 of human manganese SOD is also nitrated, suggesting that this might be an evolutionarily conserved mechanism for regulation of manganese SODs. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  14. Profile of non-volatiles in whisky with regard to superoxide dismutase activity.

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    Koga, Kunimasa; Tachihara, Satoshi; Shirasaka, Norifumi; Yamada, Yuri; Koshimizu, Sei-Ichi

    2011-08-01

    SOD (Superoxide dismutase)-like activities of 23 kinds of single malt whisky (Scotch and Japanese) were evaluated. There was a positive correlation between SOD-like activity and the maturation age of whisky that exceeded the difference resulting from the manufacturing region. The SOD-like activity of Yamazaki 18, a typical single malt whisky in Japan, was approximately 1333 U/ml and that of non-volatile components in the whisky was 388U/mg, indicating that single malt whisky generally has a very strong SOD-like activity. To elucidate their contribution to SOD-like activity, the non-volatile components of whisky (Yamazaki 18) were ultrafiltered and separated with a Diaion HP20/water-EtOH system. Elution of the fraction less than 5000 molecular weight (whisky. As this elution contained a considerable amount of polyphenolics, the content and SOD-like specific activity of ellagic acid, gallic acid, and lyoniresinol--the main whisky polyphenolics--were evaluated. The contribution of these compounds to the SOD-like activity of whisky was approximately 15%. Polyphenolics in whisky were relatively distributed to a higher MW fraction compared to carbohydrates in whisky, and specific activity (SOD-like activity per weight) of the >10,000 MW fraction was greater than that of the whisky together with main whisky polyphenolics.

  15. [Role of free radicals on canine bile-induced pancreatitis and effect of superoxide dismutase].

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    Sato, T

    1995-06-01

    The purpose of this study was to determine the effect of superoxide dismutase (SOD) on canine experimental pancreatitis. Pancreatitis was induced by retrograde biliary juice injection (0.5 ml/kg) to accessory pancreatic duct. Twenty-one mongrel dogs were divided into two groups, i.e. control (untreated) group (n = 13) and SOD-treated group (n = 8). In SOD-treated group, SOD 5000 units/kg was administered from celiac artery immediately after onset of pancreatitis. Xanthine oxidase (XOD), malondialdehyde (MDA), phospholipase (PL), and SOD were assayed from pancreatic tissue 1 and 3 hours after onset of pancreatitis. Serum amylase, elastase I, calcium, and WBC were assayed for 7 days after onset of pancreatitis. XOD and MDA levels were increased in untreated group, and not significantly changed in treated group with statistical difference. PL levels were increased after onset of pancreatitis in both groups and SOD levels were not changed even in treated group. No statistical difference was seen in PL and SOD levels between two groups. Increase of XOD levels suggests continuous generating of free radical species from pancreatic tissue, and SOD inhibits this increase. Increase of PL level was not improved by SOD. Serum laboratory findings and survival rates were not improved by SOD treatment.

  16. Copper–zinc superoxide dismutase-mediated redox regulation of bortezomib resistance in multiple myeloma

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    Kelley Salem

    2015-04-01

    Full Text Available Multiple myeloma (MM is an incurable B-cell malignancy. The proteasome inhibitor bortezomib (BTZ is a frontline MM drug; however, intrinsic or acquired resistance to BTZ remains a clinical hurdle. As BTZ induces oxidative stress in MM cells, we queried if altered redox homeostasis promotes BTZ resistance. In primary human MM samples, increased gene expression of copper–zinc superoxide dismutase (CuZnSOD or SOD1 correlated with cancer progression, high-risk disease, and adverse overall and event-free survival outcomes. As an in vitro model, human MM cell lines (MM.1S, 8226, U266 and the BTZ-resistant (BR lines (MM.1SBR, 8226BR were utilized to determine the role of antioxidants in intrinsic or acquired BTZ-resistance. An up-regulation of CuZnSOD, glutathione peroxidase-1 (GPx-1, and glutathione (GSH were associated with BTZ resistance and attenuated prooxidant production by BTZ. Enforced overexpression of SOD1 induced BTZ resistance and pharmacological inhibition of CuZnSOD with disulfiram (DSF augmented BTZ cytotoxicity in both BTZ-sensitive and BTZ-resistant cell lines. Our data validates CuZnSOD as a novel therapeutic target in MM. We propose DSF as an adjuvant to BTZ in MM that is expected to overcome intrinsic and acquired BTZ resistance as well as augment BTZ cytotoxicity.

  17. Copper-zinc superoxide dismutase-mediated redox regulation of bortezomib resistance in multiple myeloma.

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    Salem, Kelley; McCormick, Michael L; Wendlandt, Erik; Zhan, Fenghuang; Goel, Apollina

    2015-01-01

    Multiple myeloma (MM) is an incurable B-cell malignancy. The proteasome inhibitor bortezomib (BTZ) is a frontline MM drug; however, intrinsic or acquired resistance to BTZ remains a clinical hurdle. As BTZ induces oxidative stress in MM cells, we queried if altered redox homeostasis promotes BTZ resistance. In primary human MM samples, increased gene expression of copper-zinc superoxide dismutase (CuZnSOD or SOD1) correlated with cancer progression, high-risk disease, and adverse overall and event-free survival outcomes. As an in vitro model, human MM cell lines (MM.1S, 8226, U266) and the BTZ-resistant (BR) lines (MM.1SBR, 8226BR) were utilized to determine the role of antioxidants in intrinsic or acquired BTZ-resistance. An up-regulation of CuZnSOD, glutathione peroxidase-1 (GPx-1), and glutathione (GSH) were associated with BTZ resistance and attenuated prooxidant production by BTZ. Enforced overexpression of SOD1 induced BTZ resistance and pharmacological inhibition of CuZnSOD with disulfiram (DSF) augmented BTZ cytotoxicity in both BTZ-sensitive and BTZ-resistant cell lines. Our data validates CuZnSOD as a novel therapeutic target in MM. We propose DSF as an adjuvant to BTZ in MM that is expected to overcome intrinsic and acquired BTZ resistance as well as augment BTZ cytotoxicity.

  18. Enhanced drought tolerance of transgenic rice plants expressing a pea manganese superoxide dismutase.

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    Wang, Fang-Zheng; Wang, Qing-Bin; Kwon, Suk-Yoon; Kwak, Sang-Soo; Su, Wei-Ai

    2005-04-01

    We investigated the role that manganese superoxide dismutase (MnSOD), an important antioxidant enzyme, may play in the drought tolerance of rice. MnSOD from pea (Pisum sativum) under the control of an oxidative stress-inducible SWPA2 promoter was introduced into chloroplasts of rice (Oryza sativa) by Agrobacterium-mediated transformation to develop drought-tolerant rice plants. Functional expression of the pea MnSOD in transgenic rice plants (T1) was revealed under drought stress induced by polyethylene glycol (PEG) 6000. After PEG treatment the transgenic leaf slices showed reduced electrolyte leakage compared to wild type (WT) leaf slices, whether they were exposed to methyl viologen (MV) or not, suggesting that transgenic plants were more resistant to MV- or PEG-induced oxidative stress. Transgenic plants also exhibited less injury, measured by net photosynthetic rate, when treated with PEG. Our data suggest that SOD is a critical component of the ROS scavenging system in plant chloroplasts and that the expression of MnSOD can improve drought tolerance in rice.

  19. Tepung Rumput Laut (Eucheuma Cottonii Menaikkan Level Superoksida Dismutase (Sod Ginjal Tikus Hiperkolesterolemia

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    Tutik Wresdiyati

    2012-11-01

    Full Text Available Hypercholesterolemia condition was reported can decrease activities of antioxidant superoxidedismutase, catalase, and glutathione peroxide. This study was conducted to observe the role of seaweed(Eucheuma cottonii powder in increasing the level of antioxidant cooper, zinc-superoxide dismutase (Cu,Zn-SOD in kidney tissues of hypercholesterolemic rats. Twenty male Wistar rats were used in this study.Those rats were divided into four groups ; (1 Negative control group (A, (2 and (3 werehypercholesterolemic groups that were treated with 5% (B, and 10% (C of seaweed powder, and (4Hypercholesterolemic group as positive control (D. The treatment was carried out for 35 days.Hypercholesterolemia condition (>130 mg/dl, except for group A, was achieved by feeding the rat withcommercial diet containing 1% cholesterol and drinking water ad libitum for 40 days. Serum total cholesterolwas analyzed both before and after treatment. Rat kidneys were taken at the end of treatment, andprocessed by using paraffin embedding standard method. The tissues were then stained usingimmunohistochemical technique to Cu,Zn-SOD. The results showed the seaweed powder decreased serumtotal cholesterol, increased caecum cholesterol, repaired alteration of kidney tissues, and increased thelevel of antioxidant Cu,Zn-SOD in the kidney of hypercholesterolemic rats. Dietary fibers and antioxidantactivity of 10% seaweed powder was better than the of 5%.

  20. The Effect of Seaweed Eucheuma cottonii on Superoxide Dismutase (SOD Liver of Hypercholesterolemic Rats

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    TUTIK WRESDIYATI

    2008-09-01

    Full Text Available Intracellular antioxidant superoxide dismutase (SOD was reported decreased in the liver and kidney of hypercholesterolemic rats. This study was conducted to observe the effect of seaweed Eucheuma cottonii powder on the profile of blood cholesterol and the level of SOD in liver tissues of hypercholesterolemic rats by using immunohistochemical technique. Twenty male Wistar rats were used for this study. Those rats were divided into four groups; (i negative control group (A, (ii hypercholesterolemia group treated by 5% seaweed powder (B, (iii hypercholesterolemia group treated by 10% seaweed powder (C, and (iv Positive control group or hypercholesterolemia group (D. The experiment was carried out for 35 days. Hypercholesterolemia condition (> 130 mg/dl, except group A, was achieved by feeding the rats with commercial diet containing 1% cholesterol. Drinking water was given ad libitum for 40 days. The results showed that seaweed powder decreased the total cholesterol, low density lipoprotein (LDL, triglyceride, and increased the level of high density lipoprotein (HDL and SOD status in the liver tissues of hypercholesterolemic rats. The treatment of 10% seaweed powder gave better results than that of 5%. These results suggested that dietary fiber such in the seaweed powder has antioxidant activity.

  1. Aktivitas Enzim Superoksida Dismutase, Katalase, dan Glutation Peroksidase Wanita Penderita Sindrom Metabolik

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    Hery Winarsi

    2012-03-01

    Full Text Available The low endogenous antioxidant status induced development of metabolic syndrome (MetS condition. The aim of this research was to explore superoxide dismutase (SOD, catalase (Cat, and glutathione peroxidase (GSH-PX plasma activity on metabolic syndrome women plasma. Respondents were thirty women with blood glucose level >normal, body mass index >25 kg/m2, hypertrigliceridemic, low level cholesterol-high-density lipoprotein (HDL, the age >40 years and live in Purwokerto. Respondents’ selection was started by a survey at internist polyclinic of Margono Soekarjo General Hospital Purwokerto. They were motivated and given an explanation about aim of the research, their diseases and development risk who were willing to be respondents were asked to sign the informed consent. Then, their body weight, height and blood pressure were measured. Their blood sample of 2 mL were taken intravenously and tested for blood glucose, triglyceride and HDL levels. Plasma was tested for the activities of SOD, Cat and GSH-PX enzymes. Presented data was mean + standard error. The antioxidant status of MetS women were low, showed on the activities of SOD, catalase, and glutathione peroxidase enzyme were 379.3 Unit/mg protein, 6.42 UI/mL, 804.9 nmol/g protein respectively, and malondialdehyde (MDA level was 2,943.4 pmol/mL. Therefore, they need food enrich antioxidant. In conclusions, peroxidase antioxidant status was similar shown by low SOD, catalase and glutathione peroxidase enzyme activity

  2. Functional expression and characterization of an iron-containing superoxide dismutase of Acanthamoeba castellanii.

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    Kim, Jung-Yeon; Na, Byoung-Kuk; Song, Kyoung-Ju; Park, Mi-Hyun; Park, Yun-Kyu; Kim, Tong-Soo

    2012-10-01

    Acanthamoeba spp. are free-living amoebae, but opportunistic infections of some strains of the organisms cause severe diseases such as acanthamoebic keratitis, pneumonitis, and granulomatous amoebic encephalitis in human. In this study, we identified a gene encoding iron superoxide dismutase of Acanthamoeba castellanii (AcFe-SOD) and characterized biochemical and functional properties of the recombinant enzyme. Multiple sequence alignment of the deduced amino acid sequence of AcFe-SOD with those of previously reported iron-containing SODs (Fe-SODs) from other protozoan parasites showed that AcFe-SOD shared common metal-binding residues and motifs that are conserved in Fe-SODs. The genomic length of the AcFe-SOD gene was 926 bp consisting of five exons interrupted by four introns. The recombinant AcFe-SOD showed similar biochemical characteristics with its native enzyme and shared typical biochemical properties with other characterized Fe-SODs, including molecular structure, broad pH optimum, and sensitivity to hydrogen peroxide. Immunolocalization analysis revealed that the enzyme localized in the cytosol of the trophozoites. Activity and expression level of the enzyme were significantly increased under oxidative stressed conditions. These results collectively suggest that AcFe-SOD may play essential roles in the survival of the parasite not only by protecting itself from endogenous oxidative stress but also by detoxifying oxidative killing of the parasite by host immune effector cells.

  3. Tri-iodothyronine alters superoxide dismutase expression in a teleost Anabas testudineus.

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    Sreejith, P; Oommen, O V

    2008-12-01

    The effect of tri-iodothyronine (T3) on superoxide dismutase (SOD) expression was evaluated in a teleost Anabas testudineus (cuthyroid fish) by native gel eletrophoresis and Western blot analysis. SOD is an essential enzyme for the survival of oxygen-utilizing organisms. Its expression is altered by the stress, presumably due to the increase in concentration of superoxide radical in cells. Variations of thyroid honnone levels are the major physiological modulators of cellular oxidative stress. T3 administration generates an oxidative stress, which to some extent is neutralized by the changed activity of enzymes like SOD. T3 treatment decreased CuZn SOD density in liver and brain of A. testudineus. The activity of CuZn SOD in liver and brain was confirmed by native gel analysis. The different physiological states of thyroid influenced the CuZn SOD activity. Western blot analysis further confirmed that liver and brain CuZn SOD decreased after T3 treatment. From these findings, it was clear that T3 treatment in euthyroid fish created an oxidative stress condition and thyroid hormone effectively maintained antioxidant status to overcome this situation in teleosts.

  4. Immunohistochemical identification and quantitative analysis of cytoplasmic Cu/Zn superoxide dismutase in mouse organogenesis

    Science.gov (United States)

    Yon, Jung-Min; Baek, In-Jeoung; Lee, Se-Ra; Kim, Mi-Ra; Lee, Beom Jun; Yun, Young Won

    2008-01-01

    Cytoplasmic Cu/Zn superoxide dismutase (SOD1) is an antioxidant enzyme that converts superoxide to hydrogen peroxide in cells. Its spatial distribution matches that of superoxide production, allowing it to protect cells from oxidative stress. SOD1 deficiencies result in embryonic lethality and a wide range of pathologies in mice, but little is known about normal SOD1 protein expression in developing embryos. In this study, the expression pattern of SOD1 was investigated in post-implantation mouse embryos and extraembryonic tissues, including placenta, using Western blotting and immunohistochemical analyses. SOD1 was detected in embryos and extraembryonic tissues from embryonic day (ED) 8.5 to 18.5. The signal in embryos was observed at the lowest level on ED 9.5-11.5, and the highest level on ED 17.5-18.5, while levels remained constant in the surrounding extraembryonic tissues during all developmental stages examined. Immunohistochemical analysis of SOD1 expression on ED 13.5-18.5 revealed its ubiquitous distribution throughout developing organs. In particular, high levels of SOD1 expression were observed in the ependymal epithelium of the choroid plexus, ganglia, sensory cells of the olfactory and vestibulocochlear epithelia, blood cells and vessels, hepatocytes and hematopoietic cells of the liver, lymph nodes, osteogenic tissues, and skin. Thus, SOD1 is highly expressed at late stages of embryonic development in a cell- and tissue-specific manner, and can function as an important antioxidant enzyme during organogenesis in mouse embryos. PMID:18716442

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

    Energy Technology Data Exchange (ETDEWEB)

    Tabatabai, L.B. (ARS-USDA, Ames, IA (United States))

    1991-03-11

    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 coupled 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.

  6. Superoxide dismutase and media dependence of far-UV radiation resistance in thiol-treated cells

    Energy Technology Data Exchange (ETDEWEB)

    Claycamp, H.G.; McCormick, M.L.; DeRose, C.M.; Elwell, J.H.; Oberley, L.W. (Iowa Univ., Iowa City, IA (USA). Radiation Research Lab.)

    1990-09-01

    Pretreatment of wild-type Escherichia coli K12 cells with dithiothreitol (DTT) induces far-UV radiation resistance after the thiol is removed (Claycamp 1988). The present study shows that a 1 h treatment of cells with DTT in minimal medium followed by a 0.5 h incubation in buffer (37{sup 0}C) results in a dose reduction factor (DRF) calculated at F{sub 37} of 1.81. When the thio pretreatment was in rich medium, sensitization occurs with DRF = 0.729. This could be reversed to protection by inhibiting extracellular thiol oxidation in rich medium with the chelator, DETAPAC, such that thiol oxidation rate was equivalent to that of DTT in minimal medium. Both thiol-induced resistance and sensitization produced changes predominantly in the shoulders of survival curves. For either protection or sensitization, at least one form of endogenous superoxide dismutase (SOD) was required. These results suggest that different targets are involved in thiol-induced UV protection and sensitization: DNA and extracellular targets (e.g. the membrane), respectively. (author).

  7. Carvedilol increases copper-zinc superoxide dismutase activity in patients with acute myocardial infarction.

    Science.gov (United States)

    Kastratović, Dragana A; Vasiljević, Zorana M; Spasić, Mihajlo B; Perunicić, Jovan P; Matić, Mihajlo; Blagojević, Dusko P; Mijalković, Dejan N; Antonijević, Nebojsa M; Marković, Srdjan Z; Gojković-Bukarica, Ljiljana; Stojiljkovic, Milos P; Lasica, Ratko M; Jones, David R; Nikolić-Kokić, Aleksandra L

    2007-08-01

    Balanced and coordinated antioxidant defence enzyme activities are of utmost importance for correct physiological function and for shielding against unwelcome pathological conditions. We determined the activities of copper-zinc superoxide dismutase (CuZnSOD), catalase, glutathione peroxidase and glutathione reductase in erythrocytes isolated from patients receiving different therapy (streptokinase alone or in combination with metoprolol or with carvedilol) for up to 168 hr after starting treatment for acute myocardial infarction. We observed increased CuZnSOD activity in erythrocytes isolated from patients treated with streptokinase-carvedilol (after 6, 24 and 168 hr) and in erythrocytes isolated from patients treated with streptokinase-metoprolol (after 24 hr). In addition, positive correlation between CuZnSOD and catalase activities was found in erythrocytes isolated from patients that received streptokinase-carvedilol after 168 hr. As metoprolol does not react directly with hydrogen peroxide, it would appear that combined streptokinase-metoprolol therapy exerted its effects primarily via by beta-blockade whereas combined streptokinase-carvedilol therapy appeared to function via both beta-blockade and direct antioxidant mechanisms.

  8. Are superoxide dismutase 2 and nitric oxide synthase polymorphisms associated with idiopathic infertility?

    Science.gov (United States)

    Faure, Celine; Leveille, Pauline; Dupont, Charlotte; Julia, Chantal; Chavatte-Palmer, Pascale; Sutton, Angela; Levy, Rachel

    2014-08-01

    The aim of this study was to investigate in a case-control study the associations between idiopathic infertility and antioxidant gene polymorphisms. One hundred ten infertile subjects (58 women and 52 men) with a history of idiopathic infertility and 69 fertile subjects (35 women and 34 men) with no history of infertility were included by three hospital departments of reproductive biology in the NCT01093378 French government clinical trial. Genotyping was assessed by real-time polymerase chain reaction with TaqMan assay. We examined genetic polymorphisms affecting five antioxidant enzymes: manganese superoxide dismutase (MnSOD), myeloperoxidase (MPO), glutathione peroxidase 1 (GPx1), catalase (CAT), and endothelial nitric oxide synthase (eNOS). The presence of at least 1 Ala-MnSOD allele (rs4880) increased significantly the risk of infertility (odds ratio [OR] 2.94; 95% confidence interval [CI], 1.14, 7.60; p=0.03) in male subjects. Moreover, the presence of 2 G-eNOS allele (rs1799983) increased significantly the risk of infertility in both men and women (OR 1.91; 95% CI, 1.04, 3.54; p=0.04). Our observations lead to the hypothesis that the genetic susceptibility modulating oxidative stress may represent a risk factor for male idiopathic infertility.

  9. Superoxide dismutase: A possible protective agent against sunscald in tomatoes (lycopersicon esculentum mill.).

    Science.gov (United States)

    Rabinowitch, H D; Sklan, D

    1980-03-01

    Superoxide dismutase (SOD, EC 1.15.1.1) was concentrated from mature-green tomato fruits by gel chromatography. The enzyme was inhibited by cyanide but not by chloroform-ethanol, and appears to contain zinc and lesser amounts of copper. SOD-activity levels were high in immature green fruits, declined to a minimum in the mature-green and breaker stages known to be most susceptible to sunscald damage, increased again until the fruits were pink, and finally decreased through the red-ripe and overripe stages to the level of the mature-green fruit. When tolerance to sunscald damage was induced in mature-green fruits by controlled temperature treatment and samples of the fruits were challenged at various times during this process with a combined heat-and-light treatment known to cause sunscald, SOD activity was found to be inversely related to the susceptibility of the fruit to sunscald damage. It is suggested that superoxide is involved in sunscald injury to tomatoes and that tolerance is acquired through increases in SOD activity. Possibly SOD acts as a general protective agent against photodynamic damage to green tissues in plants that have become conditioned as the result of normal diurnal temperature fluctuations.

  10. In vitro inhibition of superoxide anion production and superoxide dismutase activity by zinc in human spermatozoa.

    Science.gov (United States)

    Gavella, M; Lipovac, V; Vucić, M; Sverko, V

    1999-08-01

    The in vitro effect of zinc on superoxide anion (O2-) generation and on SOD-like activity in spermatozoa of infertile men was investigated. The formation of superoxide anion was stimulated by NADPH and the level of superoxide anion was measured by the reduction of ferricytochrome c. Both Percoll-isolated (n = 14) and washed spermatozoa (n = 14) exposed to 1 mmol/L zinc (60 min, 37 degrees C), released less (p zinc-untreated spermatozoa. These results implicate a possible role for zinc as a scavenger of excessive superoxide anions produced by defective spermatozoa in semen after ejaculation. Additionally, zinc was found to dose-dependently inhibit superoxide dismutase (SOD)-like activity of spermatozoa in vitro. The inhibition of SOD-like activity by an equal concentration of zinc (1 mmol/L) was less pronounced in oligospermic (p zinc to inhibit SOD-like activity may be relevant to the physiological function of spermatozoa in fertilization. The evidence that zinc may elicit an inhibition of both superoxide anion production and SOD-like activity in human spermatozoa, indicate the existence of novel, zinc-related mechanism(s) involved in the oxidative events occurring after ejaculation, with a possible modulatory effect on germ cell function.

  11. Changes in manganese superoxide dismutase expression after exposure of the retina to intense light.

    Science.gov (United States)

    Yamamoto, M; Lidia, K; Gong, H; Onitsuka, S; Kotani, T; Ohira, A

    1999-02-01

    Manganese superoxide dismutase (Mn-SOD) is a naturally-occurring scavenger of superoxide, one of several reactive oxygen intermediates. To determine if Mn-SOD expression is enhanced as a defensive mechanism against oxidative challenges, such as intense light exposure, rats were exposed to cyclic light (80 lux) for 2 weeks, intense light (1,800 lux) for 24 h, and then again to cyclic light. Experimental and control (exposed to cyclic light only) eyes were enucleated 3 h, 1, 3, 7, and 14 days after light challenge. Protein expression was examined immunohistochemically using rabbit antisera against rat Mn-SOD. There was no significant difference between the light-exposed and the control groups in the thickness of the outer nuclear layers. Both retinal pigment epithelial cells and photoreceptor inner segments in the normal retina were labeled for Mn-SOD. Mn-SOD labeling was lost 3 h and day 1 after light challenge. It was re-expressed in the retinal pigment epithelial cells 3, 7, and 14 days after the light challenge, and in the photoreceptor inner segments after day 14. These results suggest that the retina might have a protective potential against light damage, in which Mn-SOD may play an important role.

  12. Homology modeling and evolutionary trace analysis of superoxide dismutase from extremophile Acidithiobacillus ferrooxidans

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The gene sod in Acidithiobacillus ferrooxidans may play a crucial role in its tolerance to the extremely acidic, toxic and oxidative environment of bioleaching. For insight into the anti-toxic mechanism of the bacteria, a three-dimensional (3D) molecular structure of the protein encoded by this gene was built by homology modeling techniques, refined by molecular dynamics simulations, assessed by PROFILE-3D and PROSTAT programs and its key residues were further detected by evolutionary trace analysis. Through these procedures, some trace residues were identified and spatially clustered. Among them, the residues of Asn38, Gly103 and Glu161 are randomly scattered throughout the mapped structure; interestingly, the other residues are all distinctly clustered in a subgroup near Fe atom. From these results, this gene can be confirmed at 3D level to encode the Fe-depending superoxide dismutase and subsequently play an anti-toxic role. Furthermore, the detected key residues around Fe binding site can be conjectured to be directly responsible for Fe binding and catalytic function.

  13. Overproduction of superoxide dismutase and catalase confers cassava resistance to Tetranychus cinnabarinus.

    Science.gov (United States)

    Lu, Fuping; Liang, Xiao; Lu, Hui; Li, Qian; Chen, Qing; Zhang, Peng; Li, Kaimian; Liu, Guanghua; Yan, Wei; Song, Jiming; Duan, Chunfang; Zhang, Linhui

    2017-01-05

    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.

  14. Exogenous Superoxide Dismutase: Action on Liver Oxidative Stress in Animals with Streptozotocin-Induced Diabetes

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    Fábio Cangeri Di Naso

    2011-01-01

    Full Text Available Aim. To investigate the effects of exogenous antioxidant copper zinc superoxide dismutase (Cu/Zn SOD on oxidative stress in the experimental model of diabetes mellitus (DM. Methods. Twenty eight male Wistar rats divided in four groups were used: control (CO, controls treated with SOD (CO + SOD, diabetics (DM, and diabetics treated with SOD (DM + SOD. SOD (orgotein, 13 mg/Kg body weight was administered. DM was induced by a single streptozotocin injection (i.p., 70 mg/kg, and 60 days later, we evaluated liver oxidative stress. Results. Liver lipoperoxidation was increased in the DM group and significantly decreased in the DM + SOD group. Nitrite and nitrate measures were reduced in the DM and increased in the DM + SOD group, while iNOS expression in the DM group was 32% greater than in the CO and 53% greater in the DM + SOD group than in the DM group (P<.01. P65 expression was 37% higher in the DM (P<.05, and there was no significant difference between the DM and DM + SOD groups. Conclusion. SOD treatment reduced liver oxidative stress in diabetic animals, even though it did not change NFκB. SOD also increased NO, probably by the increased dismutation of the superoxide radical. The iNOS expression increase, which became even more evident after SOD administration.

  15. Modification and inactivation of Cu,Zn-superoxide dismutase by the lipid peroxidation product, acrolein

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    Jung Hoon Kang

    2013-11-01

    Full Text Available Acrolein is the most reactive aldehydic product of lipidperoxidation and is found to be elevated in the brain whenoxidative stress is high. The effects of acrolein on the structureand function of human Cu,Zn-superoxide dismutase (SOD wereexamined. When Cu,Zn-SOD was incubated with acrolein, thecovalent crosslinking of the protein was increased, and the loss ofenzymatic activity was increased in a dose-dependent manner.Reactive oxygen species (ROS scavengers and copper chelatorsinhibited the acrolein-mediated Cu,Zn-SOD modification and theformation of carbonyl compound. The present study shows thatROS may play a critical role in acrolein-induced Cu,Zn-SODmodification and inactivation. When Cu,Zn-SOD that has beenexposed to acrolein was subsequently analyzed by amino acidanalysis, serine, histidine, arginine, threonine and lysine residueswere particularly sensitive. It is suggested that the modificationand inactivation of Cu,Zn-SOD by acrolein could be produced bymore oxidative cell environments. [BMB Reports 2013; 46(11:555-560

  16. Modification and inactivation of Cu,Zn-superoxide dismutase by the lipid peroxidation product, acrolein.

    Science.gov (United States)

    Kang, Jung Hoon

    2013-11-01

    Acrolein is the most reactive aldehydic product of lipid peroxidation and is found to be elevated in the brain when oxidative stress is high. The effects of acrolein on the structure and function of human Cu,Zn-superoxide dismutase (SOD) were examined. When Cu,Zn-SOD was incubated with acrolein, the covalent crosslinking of the protein was increased, and the loss of enzymatic activity was increased in a dose-dependent manner. Reactive oxygen species (ROS) scavengers and copper chelators inhibited the acrolein-mediated Cu,Zn-SOD modification and the formation of carbonyl compound. The present study shows that ROS may play a critical role in acrolein-induced Cu,Zn-SOD modification and inactivation. When Cu,Zn-SOD that has been exposed to acrolein was subsequently analyzed by amino acid analysis, serine, histidine, arginine, threonine and lysine residues were particularly sensitive. It is suggested that the modification and inactivation of Cu,Zn-SOD by acrolein could be produced by more oxidative cell environments.

  17. Effects of histone acetylation on superoxide dismutase 1 gene expression in the pathogenesis of senile cataract

    Science.gov (United States)

    Rong, Xianfang; Qiu, Xiaodi; Jiang, Yongxiang; Li, Dan; Xu, Jie; Zhang, Yinglei; Lu, Yi

    2016-01-01

    Histone acetylation plays key roles in gene expression, but its effects on superoxide dismutase 1 (SOD1) expression in senile cataract remains unknown. To address this problem, the study was to investigate the influence of histone acetylation on SOD1 expression and its effects in the pathogenesis of senile cataract. Senile cataract was classified into three types—nuclear cataract (NC), cortical cataract (CC), and posterior subcapsular cataract (SC)—using the Lens Opacities Classification System III. In senile cataracts, SOD1 expression decreased significantly. Both H3 and H4 were deacetylated at −600 bp of the SOD1 promoter of cataract lenses, and hypoacetylated at −1500, −1200, and −900 bp. In hypoacetylated histones, the hypoacetylation pattern differed among the cataracts. In vitro, anacardic acid (AA) significantly reduced H3 and H4 acetylation at the SOD1 promoter, decreased protein expression, and induced cataract formation in rabbits. AA also inhibited HLEC viability and increased cell apoptosis. In contrast, trichostatin A (TSA) was able to efficaciously stop AA’s effects on both rabbit lenses and HLECs. Decreased histone acetylation at the SOD1 promoter is associated with declined SOD1 expression in senile cataracts. Histone acetylation plays an essential role in the regulation of SOD1 expression and in the pathogenesis of senile cataracts. PMID:27703255

  18. A seeded propagation of Cu, Zn-superoxide dismutase aggregates in amyotrophic lateral sclerosis

    Science.gov (United States)

    Ogawa, Mariko; Furukawa, Yoshiaki

    2014-01-01

    Abnormal accumulation of protein inclusions in motor neurons has been known as a major pathological change in amyotrophic lateral sclerosis (ALS). Increasing numbers of proteins including mutant Cu, Zn-superoxide dismutase (SOD1) have been identified as constituents of pathological inclusions in a form of insoluble fibrillar aggregates. Notably, protein fibrillar aggregates exhibit a self-perpetuating property, which can convert a soluble native protein into insoluble fibrillar aggregates. Such “seeding reaction” of protein fibrils can accelerate the aggregation significantly and would contribute to the spread of inclusion pathologies from an affected cell to its neighboring cells in neurodegenerative diseases. In ALS, a pathological change first occurs at the site of disease onset and then propagates throughout the affected tissues in a time-dependent manner; therefore, it can be assumed that seeded aggregation may be the key factor of disease progression in ALS. In this mini review, we will briefly summarize recent studies on possible roles of a seeded aggregation of SOD1 in pathomechanism of ALS. PMID:24672430

  19. Molecular interaction mechanism between 2-mercaptobenzimidazole and copper-zinc superoxide dismutase.

    Directory of Open Access Journals (Sweden)

    Yue Teng

    Full Text Available 2-Mercaptobenzimidazole (MBI is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment is potentially harmful. In the present work, the toxic interaction of MBI with the important antioxidant enzyme copper-zinc superoxide dismutase (Cu/ZnSOD was investigated using spectroscopic and molecular docking methods. MBI can interact with Cu/ZnSOD to form an MBI-Cu/ZnSOD complex. The binding constant, number of binding sites and thermodynamic parameters were measured, which indicated that MBI could spontaneously bind with Cu/ZnSOD with one binding site through hydrogen bonds and van der Waals forces. MBI bound into the Cu/ZnSOD interface of two subdomains, which caused some microenvironmental and secondary structure changes of Cu/ZnSOD and further resulted in the inhibition of Cu/ZnSOD activity. This work provides direct evidence at a molecular level to show that exposure to MBI could induce changes in the structure and function of the enzyme Cu/ZnSOD. The estimated methods in this work may be applied to probe molecular interactions of biomacromolecules and other pollutants and drugs.

  20. Effect of Nanoparticles on Modified Screen Printed Inhibition Superoxide Dismutase Electrodes for Aluminum

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    Miriam Barquero-Quirós

    2016-09-01

    Full Text Available A novel amperometric biosensor for the determination of Al(III based on the inhibition of the enzyme superoxide dismutase has been developed. The oxidation signal of epinephrine substrate was affected by the presence of Al(III ions leading to a decrease in its amperometric current. The immobilization of the enzyme was performed with glutaraldehyde on screen-printed carbon electrodes modifiedwith tetrathiofulvalene (TTF and different types ofnanoparticles. Nanoparticles of gold, platinum, rhodium and palladium were deposited on screen printed carbon electrodes by means of two electrochemical procedures. Nanoparticles were characterized trough scanning electronic microscopy, X-rays fluorescence, and atomic force microscopy. Palladium nanoparticles showed lower atomic force microscopy parameters and higher slope of aluminum calibration curves and were selected to perform sensor validation. The developed biosensor has a detection limit of 2.0 ± 0.2 μM for Al(III, with a reproducibility of 7.9% (n = 5. Recovery of standard reference material spiked to buffer solution was 103.8% with a relative standard deviation of 4.8% (n = 5. Recovery of tap water spiked with the standard reference material was 100.5 with a relative standard deviation of 3.4% (n = 3. The study of interfering ions has also been carried out.

  1. Conformational Disorder of the Most Immature Cu, Zn-Superoxide Dismutase Leading to Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Furukawa, Yoshiaki; Anzai, Itsuki; Akiyama, Shuji; Imai, Mizue; Cruz, Fatima Joy C; Saio, Tomohide; Nagasawa, Kenichi; Nomura, Takao; Ishimori, Koichiro

    2016-02-19

    Misfolding of Cu,Zn-superoxide dismutase (SOD1) is a pathological change in the familial form of amyotrophic lateral sclerosis caused by mutations in the SOD1 gene. SOD1 is an enzyme that matures through the binding of copper and zinc ions and the formation of an intramolecular disulfide bond. Pathogenic mutations are proposed to retard the post-translational maturation, decrease the structural stability, and hence trigger the misfolding of SOD1 proteins. Despite this, a misfolded and potentially pathogenic conformation of immature SOD1 remains obscure. Here, we show significant and distinct conformational changes of apoSOD1 that occur only upon reduction of the intramolecular disulfide bond in solution. In particular, loop regions in SOD1 lose their restraint and become significantly disordered upon dissociation of metal ions and reduction of the disulfide bond. Such drastic changes in the solution structure of SOD1 may trigger misfolding and fibrillar aggregation observed as pathological changes in the familial form of amyotrophic lateral sclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Correction of iron deficiency anemia in pregnancy and its effects on superoxide dismutase.

    Science.gov (United States)

    Khalid, Shamaila; Ahmad, Syed Iqbal

    2012-04-01

    Iron deficiency anemia (IDA) affects not only the hematological parameters but also disturb the oxidative balance of body. In pregnancy, this is much more considerable as oxidative stress is considered to be one of the physiological changes during this period. This study aims to observe the effect of daily iron supplement on oxidative stress in pregnancy. In this study, 30 pregnant women with IDA were treated with daily oral iron supplements for 12 weeks. After 12 weeks hemoglobin (Hb), hematocrit, serum ferritin concentration (SFC) and superoxide dismutase (SOD) activity were measured and compared with pre-supplement levels. A significant increase in all the parameters was observed after treatment (p<0.05). When post supplemental values of SFC and SOD were compared with control group comprising of 10 non anemic pregnant women, they were significantly low (p<0.05). Our results indicate that oxidative stress in pregnancy associated with IDA decreases with daily iron supplements but fail to reach normal pregnant levels. This supports iron over load theory in daily iron supplements and suggests that oxidative stress increases if pregnancy is associated with iron deficiency.

  3. Role of superoxide dismutase in hepatitis B virus-related hepatocellular carcinoma

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    Xiaolian Zhang

    2016-01-01

    Full Text Available Background: Reactive oxygen species (ROS play important roles in hepatocarcinogenesis. Superoxide dismutase (SOD is involved in the repair of ROS. Serum alpha-fetoprotein (AFP is the “golden marker” for diagnosing hepatocellular carcinoma (HCC, and one major shortcoming of its use is that it is insensitive for the early detection of HCC. Therefore, we evaluated serum SOD levels and their association with AFP in hepatitis B virus (HBV-related HCC. Materials and Methods: A total of 279 subjects were divided into three groups: 99 HBV patients with HCC, 73 HBV patients without HCC, and 107 sex- and age-matched healthy controls. Serum levels of SOD were assayed using colorimetry, while AFP levels were measured by electrochemiluminescence immunoassay. Results: A highly significant elevation was found in AFP in HBV-with HCC patients compared to HBV-without HCC patients and control subjects (P < 0.001. Alternatively, serum SOD levels were significantly decreased in patients with HCC compared to HBV patients without HCC and healthy controls (P < 0.001. Furthermore, serum SOD was negatively correlated with AFP (r = −0.505, P < 0.001 in HBV-with HCC patients. Conclusion: SOD and AFP might be simultaneously evaluated to improve the HCC detection rate.

  4. Localization and distribution of superoxide dismutase-1 in the neural tube morphogenesis of chick embryo.

    Science.gov (United States)

    Dhage, Prajakta A; Kamble, Lekha K; Bhargava, Shobha Y

    2017-02-01

    Superoxide dismutase 1 (SOD- 1) is an antioxidant enzyme that regulates the levels of Reactive oxygen species (ROS) by catalyzing the conversion of superoxide radical into hydrogen peroxide (H2O2) and oxygen. ROS are known to play a significant role in various cellular processes, via redox modification of a variety of molecules that participate in signaling pathways involved in this processes. As the levels of ROS in cells are controlled by the levels of antioxidant enzymes, thus SOD-1 may be indirectly involved in regulating different cellular processes by maintaining the required levels of H2O2. Therefore, in the present study we have investigated the possible involvement of SOD- 1 in the neurulation during the development of chick embryo. During gastrulation, SOD- 1 immunoreactivity was observed throughout the ectoderm and cauda mesoderm areas, however, its presence during neurulation was restricted to certain areas of neural tube particularly in the dorsal neural tube where neural tube closure takes place. Assaying enzyme activity revealed a significant increase in the SOD activity during neurulation. Further, inhibition of SOD- 1 by Diethyldithiocarbamate (DDC) induced abnormalities in the development of the neural tube. SOD- 1 inhibition specifically affected the closure of neural tube in the anterior region. Thus, here we report the presence of SOD- 1 mainly in the ectoderm and tissues of ectodermal origin during gastrulation to neurulation which suggests that it may be involved in the regulating the cellular processes during neural tube morphogenesis.

  5. Tempol, a Superoxide Dismutase-Mimetic Drug, Ameliorates Progression of Renal Disease in CKD Mice

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    Wei Ding

    2015-07-01

    Full Text Available Background: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD and antioxidants may ameliorate disease progression. We investigate the beneficial effect of Tempol, a superoxide dismutase-mimetic drug, on progression of disease in a mouse model of CKD. Methods: CKD was surgically induced in c57BL/6 mice by 5/6 nephrectomy. Mice were randomly divided into 3 groups: sham group, 5/6 nephrectomized group (Nx and Nx+Tempol (2 mmol/l in drinking water. Mice were sacrificed at the end of 12 weeks. Renal function, structure as well as expression of key molecules involved in the pathogenesis of inflammation, fibrosis and progression in mice were measured. Results: Reduced body weight and impaired renal function (elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage was demonstrated in Nx mice but was significantly improved by Tempol administration. Nx animals exhibited significantly elevated proinflammatory and profibrotic factors, activation of NF-κB, increased expression of NADPH oxidase related subunits (p47phox, p67phox, gp91phox, and elevated activation of TGF-ß/Smad3, EGFR, MAPK signaling pathway. Tempol inhibited NF-κB mediated inflammation, TGF-ß/Smad3-induced renal fibrosis as well as EGFR and MAPK signaling pathway activation. Conclusions: Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-ß/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways.

  6. Brain beta-amyloid accumulation in transgenic mice expressing mutant superoxide dismutase 1.

    Science.gov (United States)

    Turner, Bradley J; Li, Qiao-Xin; Laughton, Katrina M; Masters, Colin L; Lopes, Elizabeth C; Atkin, Julie D; Cheema, Surindar S

    2004-12-01

    Oxidative stress is implicated in both the deposition and pathogenesis of beta-amyloid (Abeta) protein in Alzheimer's disease (AD). Accordingly, overexpression of the antioxidant enzyme superoxide dismutase 1 (SOD1) in neuronal cells and transgenic AD mice reduces Abeta toxicity and accumulation. In contrast, mutations in SOD1 associated with amyotrophic lateral sclerosis (ALS) confer enhanced pro-oxidative enzyme activities. We therefore examined whether ALS-linked mutant SOD1 overexpression in motor neuronal cells or transgenic ALS mice modulates Abeta toxicity or its accumulation in the brain. Aggregated, but not freshly solubilised, substrate-bound Abeta peptides induced degenerative morphology and cytotoxicity in motor neuron-like NSC-34 cells. Transfection of NSC-34 cells with human wild-type SOD1 attenuated Abeta-induced toxicity, however this neuroprotective effect was also observed for ALS-linked mutant SOD1. Analysis of the cerebral cortex, brainstem, cerebellum and olfactory bulb from transgenic SOD1G93A mice using enzyme-linked immunosorbent assay of acid-guanidine extracts revealed age-dependent elevations in Abeta levels, although not significantly different from wild-type mouse brain. In addition, brain amyloid protein precursor (APP) levels remained unaltered as a consequence of mutant SOD1 expression. We therefore conclude that mutant SOD1 overexpression promotes neither Abeta toxicity nor brain accumulation in these ALS models.

  7. A superoxide dismutase/catalase mimetic nanomedicine for targeted therapy of inflammatory bowel disease.

    Science.gov (United States)

    Zhang, Qixiong; Tao, Hui; Lin, Yongyao; Hu, Ying; An, Huijie; Zhang, Dinglin; Feng, Shibin; Hu, Houyuan; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

    2016-10-01

    Oxidative stress, resulting from excessive generation of reactive oxygen species (ROS), plays a pivotal role in the initiation and progression of inflammatory bowel disease (IBD). To develop an efficacious and safe nanotherapy against IBD, we designed and developed a superoxide dismutase/catalase mimetic nanomedicine comprising a hydrogen peroxide-eliminating nanomatrix and a free radical scavenger Tempol (Tpl). To this end, an oxidation-responsive β-cyclodextrin material (OxbCD) was synthesized, and a Tpl-loaded OxbCD nanoparticle (Tpl/OxbCD NP) was produced. Hydrolysis of OxbCD NP could be triggered by hydrogen peroxide, leading to on-demand release of loaded Tpl molecules from Tpl/OxbCD NP. OxbCD NP was able to efficiently accumulate in the inflamed colon in mice, thereby dramatically reducing nonspecific distribution after oral delivery. In three mouse colitis models, oral administration of Tpl/OxbCD NP notably mitigated manifestations relevant to colitis, and significantly suppressed expression of proinflammatory mediators, with the efficacy superior over free Tpl or a control nanomedicine based on poly(lactide-co-glycolide) (PLGA). Accordingly, by scavenging multiple components of ROS, Tpl/OxbCD NP may effectively reduce ulcerative colitis in mice, and it can be intensively developed as a translational nanomedicine for the management of IBD and other inflammatory diseases.

  8. Multiple phytoestrogens inhibit cell growth and confer cytoprotection by inducing manganese superoxide dismutase expression.

    Science.gov (United States)

    Robb, Ellen L; Stuart, Jeffrey A

    2014-01-01

    Phytoestrogens are of interest because of their reported beneficial effects on many human maladies including cancer, neurodegeneration, cardiovascular disease and diabetes. As data on phytoestrogens continues to accumulate, it is clear that there is significant overlap in the cellular effects elicited by these various compounds. Here, we show that one mechanism by which a number of phytoestrogens achieve their growth inhibitory and cytoprotective effects is via induction of the mitochondrial manganese superoxide dismutase (MnSOD). Eight phytoestrogens, including resveratrol, coumestrol, kaempferol, genistein, daidzein, apigenin, isoliquirtigenin and glycitin, were tested for their ability to induce MnSOD expression in mouse C2C12 and primary myoblasts. Five of these, resveratrol, coumestrol, kaempferol, genistein and daidzein, significantly increased MnSOD expression, slowed proliferative growth and enhanced stress resistance (hydrogen peroxide LD50) . When siRNA was used to prevent the MnSOD induction by genistein, coumestrol or daidzein, none of these compounds exerted any effect on proliferative growth, and only the effect of coumestrol on stress resistance persisted. The estrogen antagonist ICI182780 prevented the increased MnSOD expression and also the changes in cell growth and stress resistance, indicating that these effects are mediated by estrogen receptors (ER). The absence of effects of resveratrol or coumestrol, but not genistein, in ERβ-null cells further indicated that this ER in particular is important in mediating these effects. Thus, an ER-mediated induction of MnSOD expression appears to underlie the growth inhibitory and cytoprotective activities of multiple phytoestrogens.

  9. The Effect of UV-B Radiation on Bufo arenarum Embryos Survival and Superoxide Dismutase Activity

    Science.gov (United States)

    Herkovits, J.; D’Eramo, J. L.; Fridman, O.

    2006-01-01

    The exposure of Bufo arenarum embryos to 300–310 nm UV-B at a dose of 4,104 Joule/m2 resulted in 100% lethality within 24 hr while 820 Joule/m2 was the NOEC value for short-term chronic (10 days) exposure. The dose response curves show that lethal effects are proportional with the dose and achieve its highest value within 48 hr post exposure. The superoxide dismutase (SOD) activity in amphibian embryos for sublethal UV-B exposures was evaluated by means of UV-B treatments with 273 (A), 820(B), 1368(C) and 1915(D) Joule/m2 at 2 and 5 hours post irradiation. The SOD activity in units/mg protein in A, B, C and D at 2 hr after treatments were 80.72 ± 14.29, 74.5 ± 13.19, 39.5 ± 6.99 and 10.7 ± 1.89 respectively while for control embryos it was 10.88 ± 1.31. At 5 hr after treatments the SOD values were similar to those found in control embryos. The results confirm the high susceptibility of amphibian embryos to UV-B and point out that the SOD activity is enhanced by low doses of UV-B irradiation achieving significantly higher values than in control embryos at 2 hr post exposure. PMID:16823076

  10. Differential expression of superoxide dismutase genes in aphid-stressed maize (Zea mays L.) seedlings.

    Science.gov (United States)

    Sytykiewicz, Hubert

    2014-01-01

    The aim of this study was to compare the expression patterns of superoxide dismutase genes (sod2, sod3.4, sod9 and sodB) in seedling leaves of the Zea mays L. Tasty Sweet (susceptible) and Ambrozja (relatively resistant) cultivars infested with one of two hemipteran species, namely monophagous Sitobion avenae F. (grain aphid) or oligophagous Rhopalosiphum padi L. (bird cherry-oat aphid). Secondarily, aphid-elicited alternations in the antioxidative capacity towards DPPH (1,1-diphenyl-2-picrylhydrazyl) radical in insect-stressed plants were evaluated. Comprehensive comparison of expression profiles of the four sod genes showed that both insect species evoked significant upregulation of three genes sod2, sod3.4 and sod9). However, aphid infestation affected non-significant fluctuations in expression of sodB gene in seedlings of both maize genotypes. The highest levels of transcript accumulation occurred at 8 h (sod2 and sod3.4) or 24 h (sod9) post-infestation, and aphid-induced changes in the expression of sod genes were more dramatic in the Ambrozja cultivar than in the Tasty Sweet variety. Furthermore, bird cherry-oat aphid colonization had a more substantial impact on levels of DPPH radical scavenging activity in infested host seedlings than grain aphid colonization. Additionally, Ambrozja plants infested by either hemipteran species showed markedly lower antioxidative capacity compared with attacked Tasty Sweet plants.

  11. Effect of Nanoparticles on Modified Screen Printed Inhibition Superoxide Dismutase Electrodes for Aluminum

    Science.gov (United States)

    Barquero-Quirós, Miriam; Arcos-Martínez, María Julia

    2016-01-01

    A novel amperometric biosensor for the determination of Al(III) based on the inhibition of the enzyme superoxide dismutase has been developed. The oxidation signal of epinephrine substrate was affected by the presence of Al(III) ions leading to a decrease in its amperometric current. The immobilization of the enzyme was performed with glutaraldehyde on screen-printed carbon electrodes modifiedwith tetrathiofulvalene (TTF) and different types ofnanoparticles. Nanoparticles of gold, platinum, rhodium and palladium were deposited on screen printed carbon electrodes by means of two electrochemical procedures. Nanoparticles were characterized trough scanning electronic microscopy, X-rays fluorescence, and atomic force microscopy. Palladium nanoparticles showed lower atomic force microscopy parameters and higher slope of aluminum calibration curves and were selected to perform sensor validation. The developed biosensor has a detection limit of 2.0 ± 0.2 μM for Al(III), with a reproducibility of 7.9% (n = 5). Recovery of standard reference material spiked to buffer solution was 103.8% with a relative standard deviation of 4.8% (n = 5). Recovery of tap water spiked with the standard reference material was 100.5 with a relative standard deviation of 3.4% (n = 3). The study of interfering ions has also been carried out. PMID:27681735

  12. Differential expression of superoxide dismutase genes in aphid-stressed maize (Zea mays L. seedlings.

    Directory of Open Access Journals (Sweden)

    Hubert Sytykiewicz

    Full Text Available The aim of this study was to compare the expression patterns of superoxide dismutase genes (sod2, sod3.4, sod9 and sodB in seedling leaves of the Zea mays L. Tasty Sweet (susceptible and Ambrozja (relatively resistant cultivars infested with one of two hemipteran species, namely monophagous Sitobion avenae F. (grain aphid or oligophagous Rhopalosiphum padi L. (bird cherry-oat aphid. Secondarily, aphid-elicited alternations in the antioxidative capacity towards DPPH (1,1-diphenyl-2-picrylhydrazyl radical in insect-stressed plants were evaluated. Comprehensive comparison of expression profiles of the four sod genes showed that both insect species evoked significant upregulation of three genes sod2, sod3.4 and sod9. However, aphid infestation affected non-significant fluctuations in expression of sodB gene in seedlings of both maize genotypes. The highest levels of transcript accumulation occurred at 8 h (sod2 and sod3.4 or 24 h (sod9 post-infestation, and aphid-induced changes in the expression of sod genes were more dramatic in the Ambrozja cultivar than in the Tasty Sweet variety. Furthermore, bird cherry-oat aphid colonization had a more substantial impact on levels of DPPH radical scavenging activity in infested host seedlings than grain aphid colonization. Additionally, Ambrozja plants infested by either hemipteran species showed markedly lower antioxidative capacity compared with attacked Tasty Sweet plants.

  13. Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition

    Directory of Open Access Journals (Sweden)

    Randi H. Gottfredsen

    2013-01-01

    Full Text Available Superoxide dismutase (EC-SOD controls the level of superoxide in the extracellular space by catalyzing the dismutation of superoxide into hydrogen peroxide and molecular oxygen. In addition, the enzyme reacts with hydrogen peroxide in a peroxidase reaction which is known to disrupt enzymatic activity. Here, we show that the peroxidase reaction supports a site-specific bond cleavage. Analyses by peptide mapping and mass spectrometry shows that oxidation of Pro112 supports the cleavage of the Pro112–His113 peptide bond. Substitution of Ala for Pro112 did not inhibit fragmentation, indicating that the oxidative fragmentation at this position is dictated by spatial organization and not by side-chain specificity. The major part of EC-SOD inhibited by the peroxidase reaction was not fragmented but found to encompass oxidations of histidine residues involved in the coordination of copper (His98 and His163. These oxidations are likely to support the dissociation of copper from the active site and thus loss of enzymatic activity. Homologous modifications have also been described for the intracellular isozyme, Cu/Zn-SOD, reflecting the almost identical structures of the active site within these enzymes. We speculate that the inactivation of EC-SOD by peroxidase activity plays a role in regulating SOD activity in vivo, as even low levels of superoxide will allow for the peroxidase reaction to occur.

  14. A novel selenium and copper-containing peptide with both superoxide dismutase and glutathione peroxidase activities.

    Science.gov (United States)

    Zou, Xian-Feng; Ji, Yue-Tong; Gao, Gui; Zhu, Xue-Jun; Lv, Shao-Wu; Yan, Fei; Han, Si-Ping; Chen, Xing; Gao, Chang-Cheng; Liu, Junqiu; Luo, Gui-Min

    2010-01-01

    Superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) play crucial roles in balancing the production and decomposition of reactive oxygen species (ROS) in living organisms. These enzymes act cooperatively and synergistically to scavenge ROS. In order to imitate the synergism of these enzymes, we designed and synthesized a novel 32-mer peptide (32P) on the basis of the previous 15-mer peptide with GPX activity and a 17-mer peptide with SOD activity. Upon the selenation and chelation of copper, the 32-mer peptide is converted to a new Se- and Cu-containing 32-mer peptide (Se-Cu-32P) and displays both SOD and GPX activities and its kinetics was studied. Moreover, the novel peptide was demonstrated to be able to better protect vero cells from the injury induced by xanthine oxidase (XOD)/xanthine/Fe2+ damage system than its parents. Thus, this bifunctional enzyme imitated the synergism of SOD and GPX and could be a better candidate of therapeutic medicine.

  15. Purification and Characterization of Superoxide Dismutase(SOD) from Camellia Pollen

    Institute of Scientific and Technical Information of China (English)

    HE Xiao-hong; WU Min; LI Shan-yu; FAN Hao; CHU Yu-zhuo; LIU Lan-ying

    2005-01-01

    A superoxide dismutase(SOD) was purified to homogeneity from fresh camellia pollen by means of ammonium sulfate precipitation and column chromatography with DEAE-cellulose(DE52), Sephadex G-100 and phenyl sepharoseTM 6 Fast Flow columns. Its specific activity could reach to 4034 U/mg protein and it was determined to be Cu/Zn-SOD according to its different sensitivities to different inhibitors. The molecular weight of the SOD and its subunit were 69500 and 34700, respectively, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE), which implicates that the SOD in camellia pollen is a dimmer composed of two identical subunits. The iso-electric point of the enzyme was determined to be 4.1 by isoelectric focusing electrophoresis and the N-terminal amino acid was identified to be Gly by the DNS-Cl method. Its α-Helix was also calculated to be approximately 21.8% according to the circular dichroism(CD) spectra.

  16. THE BALANCE BETWEEN SUPEROXIDE DISMUTASE AND CATALASE ACTIVITIES IN SERA OF OBESE IRAQI MEN.

    Directory of Open Access Journals (Sweden)

    Abdulsamie H. Alta'ee

    2015-04-01

    Full Text Available Obesity is a multifaceted disorder stemming from an imbalance in the homeostasis of energy, which leads to an accumulation of excess energy as fat. It has become of increasing concern in the Iraqi population since 2003, when obesity was identified as a significant factor in relation to several diseases. The objective of this study is to investigate the association between oxidative stress and obesity in blood serum of obese Iraqi men. This study was conducted on two different groups with matching age ranges (25-35 years. The obese group consisted of thirty-six obese subjects with varying grades of obesity (BMI 40 ± 5 kg/m2 . The control group included thirty-six non-obese subjects (BMI 25 ± 3 kg/m2 . There are two parallel components to this study: The first involves Superoxide dismutase activity, catalase activity and total thiol group levels as a marker of antioxidants. The second involves the end product of lipid peroxidation (MDA as a marker of oxidative stress. When compared with the control group, SOD, CAT activity, and MDA were significantly increased, whereas TTG was significantly decreased. There is a balance between CAT activity compared with SOD activity and polyunsaturated fatty acids hydroxyl peroxide that play a vital role in the regulation of ROS and the body's defense system in obese men and in the human body in general.

  17. Purification and Properties of Superoxide Dismutase(SOD) in Allium Sativum

    Institute of Scientific and Technical Information of China (English)

    TENG Li-rong; WANG Ya-jun; WU Min; HONG Shui-sheng; CHEN Jia; Meng Qing-fan; LIU Lan-ying

    2003-01-01

    Superoxide dismutases(SODs) were purified to homogeneity from Allium Sativum by means of ammonium sulfate precipitation and column chromatography with DEAE-cellulose(DE52) and Sephadex G-75. Based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-AGE), Allium Sativum is predicted to contain four SODs. The molecular weights of the native SODs are 41.3 kD, 37.0 kD, 35.2 kD and 31.0 kD, which consist of subunits of 20.7 kD, 18.4 kD, 17.7 kD and 15.4 kD respectively. Because of their specific sensitivity to hydrogen peroxide, cyanogens potassium and chloroform-alcohol, the SODs in Allium Sativum appear to be Cu, Zn-SOD isoenzymes. The isoelectric analysis indicates that three of the four isoenzymes are acidic proteins with isoelectric points at pH 3.5, 3.7 and 4.0, respectively, and the fourth one is a basic protein with isoeletric point at pH 8.5.

  18. Cloning, expression and characterization of mitochondrial manganese superoxide dismutase from the Whitefly, Bemisia tabaci.

    Science.gov (United States)

    Gao, Xian-Long; Li, Jun-Min; Wang, Yong-Liang; Jiu, Min; Yan, Gen-Hong; Liu, Shu-Sheng; Wang, Xiao-Wei

    2013-01-07

    A mitochondrial manganese superoxide dismutase from an invasive species of the whitefly Bemisia tabaci complex (Bt-mMnSOD) was cloned and analyzed. The full length cDNA of Bt-mMnSOD is 1210 bp with a 675 bp open reading frame, corresponding to 224 amino acids, which include 25 residues of the mitochondrial targeting sequence. Compared with various vertebrate and invertebrate animals, the MnSOD signature (DVWEHAYY) and four conserved amino acids for manganese binding (H54, H102, D186 and H190) were observed in Bt-mMnSOD. Recombinant Bt-mMnSOD was overexpressed in Escherichia coli, and the enzymatic activity of purified mMnSOD was assayed under various temperatures. Quantitative real-time PCR analysis with whiteflies of different development stages showed that the mRNA levels of Bt-mMnSOD were significantly higher in the 4th instar than in other stages. In addition, the in vivo activities of MnSOD in the whitefly were measured under various conditions, including exposure to low (4 °C) and high (40 °C) temperatures, transfer from a favorable to an unfavorable host plant (from cotton to tobacco) and treatment with pesticides. Our results indicate that the whitefly MnSOD plays an important role in cellular stress responses and anti-oxidative processes and that it might contribute to the successful worldwide distribution of the invasive whitefly.

  19. Superoxide Dismutase (SOD Enzyme Activity Assay in Fasciola spp. Para-sites and Liver Tissue Extract

    Directory of Open Access Journals (Sweden)

    M Assady

    2011-09-01

    Full Text Available Background: The purpose of this comparative study was to detect superoxide dismutase (SOD activities in Fasciola hepatica, F. gigantica parasites, infected and healthy liver tissues in order to determine of species effects and liver infection on SODs activity level.Methods: Fasciola spp. parasites and sheep liver tissues (healthy and infected liver tissues, 10 samples for each, were collected, homogenized and investigated for protein measurement, protein detection and SOD enzyme activity assay. Protein concentration was measured by Bradford method and SODs band protein was detected on SDS-PAGE. SODs activity was determined by iodonitrotetrazolium chloride, INT, and xanthine substrates. Independent samples t-test was conducted for analysis of SODs activities difference.Results: Protein concentration means were detected for F. hepatica 1.3 mg/ ml, F. gigantica 2.9 mg/ml, healthy liver tissue 5.5 mg/ml and infected liver tissue 1.6 mg/ml (with similar weight sample mass. Specific enzyme activities in the samples were obtained 0.58, 0.57, 0.51, 1.43 U/mg for F. hepatica, F. gigantica, healthy liver and infected liver respectively. Gel electrophoresis of Fasciola spp. and sheep liver tissue extracts revealed a band protein with MW of 60 kDa. The statistical analysis revealed significant difference between SOD activities of Fasciola species and also between SOD activity of liver tissues (P<.05.Conclusion: Fasciola species and liver infection are effective causes on SOD enzyme activity level.

  20. Conditional radioresistance of Tet-inducible manganese superoxide dismutase bone marrow stromal cell lines.

    Science.gov (United States)

    Epperly, Michael W; Chaillet, J Richard; Kalash, Ronny; Shaffer, Ben; Goff, Julie; Franicola, Darcy; Zhang, Xichen; Dixon, Tracy; Houghton, Frank; Wang, Hong; Berhane, Hebist; Romero, Cynthia; Kim, Jee-Hong; Greenberger, Joel S

    2013-08-01

    Mitochondrial targeted manganese superoxide dismutase is a major antioxidant enzyme, the levels of which modulate the response of cells, tissues and organs to ionizing irradiation. We developed a Tet-regulated MnSOD mouse (MnSOD(tet)) to examine the detailed relationship between cellular MnSOD concentration and radioresistance and carried out in vitro studies using bone marrow culture derived stromal cell lines (mesenchymal stem cells). Homozygous MnSOD(tet/tet) cells had low levels of MnSOD, reduced viability and proliferation, increased radiosensitivity, elevated overall antioxidant stores, and defects in cell proliferation and DNA strand-break repair. Doxycycline (doxy) treatment of MnSOD(tet/tet) cells increased MnSOD levels and radioresistance from ñ of 2.79 ± 1.04 to 8.69 ± 1.09 (P = 0.0060) and normalized other biologic parameters. In contrast, MnSOD(tet/tet) cells showed minimal difference in baseline and radiation induced mRNA and protein levels of TGF-β, Nrf2 and NF-κB and radiation induced cell cycle arrest was not dependent upon MnSOD level. These novel MnSOD(tet/tet) mouse derived cells should be valuable for elucidating several parameters of the oxidative stress response to ionizing radiation.

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

    Science.gov (United States)

    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.

  2. N-Acetyl Cysteine Inhibits Endothelin-1-Induced ROS Dependent Cardiac Hypertrophy through Superoxide Dismutase Regulation

    Directory of Open Access Journals (Sweden)

    Sobia Mushtaq

    2015-07-01

    Full Text Available Objective: Oxidative stress down regulates antioxidant enzymes including superoxide dismutase (SOD and contributes to the development of cardiac hypertrophy. N-Acetyl cysteine (NAC can enhance the SOD activity, so the aim of this study is to highlight the inhibitory role of NAC against endothelin-1 (ET-1-induced cardiac hypertrophy. Materials and Methods: In this experimental study at QAU from January, 2013 to March, 2013. ET-1 (50 μg/kg and NAC (50 mg/kg were given intraperitoneally to 6-day old neonatal rats in combination or alone. All rats were sacrificed 15 days after the final injection. Histological analysis was carried out to observe the effects caused by both drugs. Reactive oxygen species (ROS analysis and SOD assay were also carried out. Expression level of hypertrophic marker, brain natriuretic peptide (BNP, was detected by western blotting. Results: Our findings showed that ET-1-induced cardiac hypertrophy leading towards heart failure was due to the imbalance of different parameters including free radical-induced oxidative stress and antioxidative enzymes such as SOD. Furthermore NAC acted as an antioxidant and played inhibitory role against ROS-dependent hypertrophy via regulatory role of SOD as a result of oxidative response associated with hypertrophy. Conclusion: ET-1-induced hypertrophic response is associated with increased ROS production and decreased SOD level, while NAC plays a role against free radicals-induced oxidative stress via SOD regulation.

  3. Brain-Specific Superoxide Dismutase 2 Deficiency Causes Perinatal Death with Spongiform Encephalopathy in Mice.

    Science.gov (United States)

    Izuo, Naotaka; Nojiri, Hidetoshi; Uchiyama, Satoshi; Noda, Yoshihiro; Kawakami, Satoru; Kojima, Shuji; Sasaki, Toru; Shirasawa, Takuji; Shimizu, Takahiko

    2015-01-01

    Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, including neurodegeneration. Impairment of mitochondrial energy production and increased mitochondrial oxidative damage are considered early pathological events that lead to neurodegeneration. Manganese superoxide dismutase (Mn-SOD, SOD2) is a mitochondrial antioxidant enzyme that converts toxic superoxide to hydrogen peroxide. To investigate the pathological role of mitochondrial oxidative stress in the central nervous system, we generated brain-specific SOD2-deficient mice (B-Sod2(-/-)) using nestin-Cre-loxp system. B-Sod2(-/-) showed perinatal death, along with severe growth retardation. Interestingly, these mice exhibited spongiform neurodegeneration in motor cortex, hippocampus, and brainstem, accompanied by gliosis. In addition, the mutant mice had markedly decreased mitochondrial complex II activity, but not complex I or IV, in the brain based on enzyme histochemistry. Furthermore, brain lipid peroxidation was significantly increased in the B-Sod2(-/-), without any compensatory alterations of the activities of other antioxidative enzymes, such as catalase or glutathione peroxidase. These results suggest that SOD2 protects the neural system from oxidative stress in the perinatal stage and is essential for infant survival and central neural function in mice.

  4. Brain-Specific Superoxide Dismutase 2 Deficiency Causes Perinatal Death with Spongiform Encephalopathy in Mice

    Directory of Open Access Journals (Sweden)

    Naotaka Izuo

    2015-01-01

    Full Text Available Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, including neurodegeneration. Impairment of mitochondrial energy production and increased mitochondrial oxidative damage are considered early pathological events that lead to neurodegeneration. Manganese superoxide dismutase (Mn-SOD, SOD2 is a mitochondrial antioxidant enzyme that converts toxic superoxide to hydrogen peroxide. To investigate the pathological role of mitochondrial oxidative stress in the central nervous system, we generated brain-specific SOD2-deficient mice (B-Sod2−/− using nestin-Cre-loxp system. B-Sod2−/− showed perinatal death, along with severe growth retardation. Interestingly, these mice exhibited spongiform neurodegeneration in motor cortex, hippocampus, and brainstem, accompanied by gliosis. In addition, the mutant mice had markedly decreased mitochondrial complex II activity, but not complex I or IV, in the brain based on enzyme histochemistry. Furthermore, brain lipid peroxidation was significantly increased in the B-Sod2−/−, without any compensatory alterations of the activities of other antioxidative enzymes, such as catalase or glutathione peroxidase. These results suggest that SOD2 protects the neural system from oxidative stress in the perinatal stage and is essential for infant survival and central neural function in mice.

  5. Molecular Characterization of a Recombinant Manganese Superoxide Dismutase from Lactococcus lactis M4

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    Boon Hooi Tan

    2014-01-01

    Full Text Available A superoxide dismutase (SOD gene of Lactococcus lactis M4 was cloned and expressed in a prokaryotic system. Sequence analysis revealed an open reading frame of 621 bp which codes for 206 amino acid residues. Expression of sodA under T7 promoter exhibited a specific activity of 4967 U/mg when induced with 1 mM of isopropyl-β-D-thiogalactopyranoside. The recombinant SOD was purified to homogeneity by immobilised metal affinity chromatography and Superose 12 gel filtration chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analyses of the recombinant SOD detected a molecular mass of approximately 27 kDa. However, the SOD was in dimer form as revealed by gel filtration chromatography. The purified recombinant enzyme had a pI of 4.5 and exhibited maximal activity at 25°C and pH 7.2. It was stable up to 45°C. The insensitivity of this lactococcal SOD to cyanide and hydrogen peroxide established that it was a MnSOD. Although it has 98% homology to SOD of L. lactis IL1403, this is the first elucidated structure of lactococcal SOD revealing active sites containing the catalytic manganese coordinated by four ligands (H-27, H-82, D-168, and H-172.

  6. Manganese superoxide dismutase (MnSOD catalyzes NO-dependent tyrosine residue nitration

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    SRDJAN STOJANOVIC

    2005-04-01

    Full Text Available The peroxynitrite-induced nitration of manganese superoxide dismutase (MnSOD tyrosine residue, which causes enzyme inactivation, is well established. This led to suggestions that MnSOD nitration and inactivation in vivo, detected in various diseases associated with oxidative stress and overproduction of nitric monoxide (NO, conditions which favor peroxynitrite formation, is also caused by peroxynitrite. However, our previous in vitro study demonstrated that exposure of MnSOD to NO led to NO conversion into nitrosonium (NO+ and nitroxyl (NO– species, which caused enzyme modifications and inactivation. Here it is reported that MnSOD is tyrosine nitrated upon exposure to NO, as well as that MnSOD nitration contributes to inactivation of the enzyme. Collectively, these observations provide a compelling argument supporting the generation of nitrating species in MnSOD exposed to NO and shed a new light on MnSOD tyrosine nitration and inactivation in vivo. This may represent a novel mechanism by which MnSOD protects cell from deleterious effects associated with overproduction of NO. However, extensive MnSOD modification and inactivation associated with prolonged exposure to NO will amplify the toxic effects caused by increased cell superoxide and NO levels.

  7. The Effect of Small Sample Size on Measurement Equivalence of Psychometric Questionnaires in MIMIC Model: A Simulation Study

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    Jamshid Jamali

    2017-01-01

    Full Text Available Evaluating measurement equivalence (also known as differential item functioning (DIF is an important part of the process of validating psychometric questionnaires. This study aimed at evaluating the multiple indicators multiple causes (MIMIC model for DIF detection when latent construct distribution is nonnormal and the focal group sample size is small. In this simulation-based study, Type I error rates and power of MIMIC model for detecting uniform-DIF were investigated under different combinations of reference to focal group sample size ratio, magnitude of the uniform-DIF effect, scale length, the number of response categories, and latent trait distribution. Moderate and high skewness in the latent trait distribution led to a decrease of 0.33% and 0.47% power of MIMIC model for detecting uniform-DIF, respectively. The findings indicated that, by increasing the scale length, the number of response categories and magnitude DIF improved the power of MIMIC model, by 3.47%, 4.83%, and 20.35%, respectively; it also decreased Type I error of MIMIC approach by 2.81%, 5.66%, and 0.04%, respectively. This study revealed that power of MIMIC model was at an acceptable level when latent trait distributions were skewed. However, empirical Type I error rate was slightly greater than nominal significance level. Consequently, the MIMIC was recommended for detection of uniform-DIF when latent construct distribution is nonnormal and the focal group sample size is small.

  8. Synthesis of a Hoechst 32258 analogue amino acid building block for direct incorporation of a fluorescent, high-affinity DNA binding motif into peptides

    DEFF Research Database (Denmark)

    Behrens, C; Harrit, N; Nielsen, P E

    2001-01-01

    The synthesis of a new versatile "Hoechst 33258-like" Boc-protected amino acid building block for peptide synthesis is described. It is demonstrated that this new ligand is an effective mimic of Hoechst 33258 in terms of DNA affinity and sequence specificity. Furthermore, this minor groove binder...

  9. Effects of basic fibroblast growth factor on superoxide dismutase activity and malondialdehyde content in the rat brain following intracerebral hemorrhage

    Institute of Scientific and Technical Information of China (English)

    Hongqiao Wei; Juen Huang; Junjie Huang; Bing Li; Qianming Li

    2008-01-01

    BACKGROUND: Studies have confirmed that basic fibroblast growth factor (bFGF) promotes neuronal survival and neurite outgrowth. OBJECTIVE: To compare and verify the effects of bFGF on superoxide dismutase activity and malondialdehyde content in rat brain tissues surrounding a hemorrhagic lesion, as well as the hippocampus at the hemorrhagic side. DESIGN, TIME AND SETTING: The randomized, controlled, neurobiological study was performed at the Science Experimental Center and Research Laboratory, Guangxi Medical University, China, from September to December 2006. MATERIALS: Ninety-two adult, healthy, Wistar rats of equal gender were used to establish intraeerebral hemorrhage by infusing type VII collagenase into the left internal capsule. Type Ⅶ collagenase (Sigma, USA), superoxide dismutase and malondialdehyde kits (Jiancheng, China), and bFGF (Institute of Bioengineering, Ji'nan University, China) were used for this study. METHODS: Ninety successfully lesioned rats were equally and randomly divided into three groups. Rats in the bFGF group were intramuscularly injected daily with bFGF (8μg/kg). Rats in the saline control group received an equal volume of saline. The rats in the model group did not receive other interventions. Superoxide dismutase activity was measured using the xanthine oxidase method. Malondialdehyde contents were detected using the thiobarbituric acid method. MAIN OUTCOME MEASURES: At 1, 3, and 7 days following intracerebral hemorrhage, superoxide dismutase and malondialdehyde were determined in the brain tissue surrounding the hematoma and in the hippocampus in the affected hemisphere. RESULTS: In brain tissue surrounding the hematoma, superoxide dismutase activity was significantly increased in the bFGF group at 3 and 7 days after intracerebral hemorrhage compared with the saline control group, whereas malondialdehyde content was significantly decreased (P 0.05). CONCLUSION: Increased superoxide dismutase activity and decreased

  10. Astrocytic effect of low molecular weight heparin-superoxide dismutase conjugate in interleukin-6 overexpressing mice following local cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yizhao Li; Guixiang Cui; Qingde Wang; Hongxia Liu; Xiaoxia Zhang; Fengshan Wang; Keqin Xie

    2009-01-01

    BACKGROUND: Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect.OBJECTIVE: To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 (IL-6) overexpressing mice following local cerebral ischemia.DESIGN, TIME AND SETTING: Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005.MATERIALS: Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups: sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice.Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University.METHODS: Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxicle dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment.MAIN OUTCOME MEASURES: The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy (x200).RESULTS: In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger

  11. A functional mimic of natural peroxidases : synthesis and catalytic activity of a non-heme iron/peptide hydroperoxide complex

    NARCIS (Netherlands)

    Choma, Christin T.; Schudde, Ebe P.; Kellogg, Richard M.; Robillard, George T.; Feringa, Ben L.

    1998-01-01

    Site-selective attachment of unprotected peptides to a non-heme iron complex is achieved by displacing two halides on the catalyst by peptide caesium thiolates. This coupling approach should be compatible with any peptide sequence provided there is only a single reduced cysteine. The oxidation activ

  12. Bringing Research into a First Semester Organic Chemistry Laboratory with the Multistep Synthesis of Carbohydrate-Based HIV Inhibitor Mimics

    Science.gov (United States)

    Pontrello, Jason K.

    2015-01-01

    Benefits of incorporating research experiences into laboratory courses have been well documented, yet examples of research projects designed for the first semester introductory organic chemistry lab course are extremely rare. To address this deficiency, a Carbohydrate-Based human immunodeficiency virus (HIV) Inhibitor project consisting of a…

  13. GM3, GM2 and GM1 mimics designed for biosensing: chemoenzymatic synthesis, target affinities and 900 MHz NMR analysis

    NARCIS (Netherlands)

    Pukin, A.V.; Weijers, C.A.G.M.; Lagen, van B.; Wechselberger, R.; Sun, B.; Gilbert, M.; Karwaski, M.F.; Florack, D.E.A.; Jacobs, B.C.; Tio-Gillen, A.P.; Belkum, van A.; Endtz, H.P.; Visser, G.M.; Zuilhof, H.

    2008-01-01

    Undec-10-enyl, undec-10-ynyl and 11-azidoundecyl glycoside analogues corresponding to the oligosaccharides of human gangliosides GM3, GM2 and GM1 were synthesized in high yields using glycosyltransferases from Campylobacter jejuni. Due to poor water solubility of the substrates, the reactions were

  14. Synthesis, characterization, antibacterial activity, SOD mimic and interaction with DNA of drug based copper(II) complexes

    Science.gov (United States)

    Patel, Mohan N.; Dosi, Promise A.; Bhatt, Bhupesh S.; Thakkar, Vasudev R.

    2011-02-01

    Novel metal complexes of the second-generation quinolone antibacterial agent enrofloxacin with copper(II) and neutral bidentate ligands have been prepared and characterized with elemental analysis reflectance, IR and mass spectroscopy. Complexes have been screened for their in-vitro antibacterial activity against two Gram (+ve)Staphylococcus aureus, Bacillus subtilis, and three Gram (-ve)Serratia marcescens, Escherichia coli and Pseudomonas aeruginosa organisms using the double dilution technique. The binding of this complex with CT-DNA has been investigated by absorption titration, salt effect and viscosity measurements. Binding constant is ranging from 1.3 × 10 4-3.7 × 10 4. The cleavage ability of complexes has been assessed by gel electrophoresis using pUC19 DNA. The catalytic activity of the copper(II) complexes towards the superoxide anion (O 2rad -) dismutation was assayed by their ability to inhibit the reduction of nitroblue tetrazolium (NBT).

  15. Towards squalamine mimics: synthesis and antibacterial activities of head-to-tail dimeric sterol-polyamine conjugates.

    Science.gov (United States)

    Chen, Wen-Hua; Wennersten, Christine; Moellering, Robert C; Regen, Steven L

    2013-03-01

    Four dimeric sterol-polyamine conjugates have been synthesized from the homo- and hetero-connection of monomeric sterol-polyamine analogs in a head-to-tail manner. These dimeric conjugates show strong antibacterial activity against a broad spectrum of Gram-positive bacteria, whereas their corresponding activities against Gram-negative bacteria are relatively moderate. Though no significant difference was observed in the activities of these conjugates, cholic acid-containing dimeric conjugates generally exhibit higher activities than the corresponding deoxycholic acid-derived analogs. This is in contrast to the finding that a monomeric deoxycholic acid-spermine conjugate was more active than the corresponding cholic acid-derived analog.

  16. Convenient synthesis of β-allenic α-difluoromethylenephosphonic acid monoesters: Potential synthons for cyclic phosphate mimics

    Institute of Scientific and Technical Information of China (English)

    Yun Lin; Jin Tao Liu

    2007-01-01

    β-Allenic α-difluoromethylenephosphonic acid monoesters were prepared under mild conditions for the first time by hydrolyzing the corresponding diethyl phosphonates in aqueous sodium hydroxide solution.

  17. GM3, GM2 and GM1 mimics designed for biosensing: chemoenzymatic synthesis, target affinities and 900 MHz NMR analysis

    NARCIS (Netherlands)

    Pukin, A.V.; Weijers, C.A.G.M.; van Lagen, B.; Wechselberger, R.W.; Sun, B.; Gilbert, M.; Karwaski, M.F.; Florack, D.E.A.; Jacobs, B.C.; Tio-Gillen, A.P.; van Belkum, A.; Endtz, H.P.; Visser, G.M.; Zuilhof, H.

    2008-01-01

    Undec-10-enyl, undec-10-ynyl and 11-azidoundecyl glycoside analogues corresponding to the oligosaccharides of human gangliosides GM3, GM2 and GM1 were synthesized in high yields using glycosyltransferases from Campylobacter jejuni. Due to poor water solubility of the substrates, the reactions were c

  18. Design and synthesis of a stable oxidized phospholipid mimic with specific binding recognition for macrophage scavenger receptors

    DEFF Research Database (Denmark)

    Turner, William W; Hartvigsen, Karsten; Boullier, Agnes;

    2012-01-01

    Macrophage scavenger receptors appear to play a major role in the clearance of oxidized phospholipid (OxPL) products. Discrete peptide-phospholipid conjugates with the phosphatidylcholine headgroup have been shown to exhibit binding affinity for these receptors. We report the preparation of a wat...

  19. REGENERASI DAN PERBANYAKAN RUMPUT LAUT Kappaphycus alvarezii HASIL TRANSFORMASI GEN SUPEROKSIDA DISMUTASE (MaSOD

    Directory of Open Access Journals (Sweden)

    Emma Suryati

    2017-01-01

    Full Text Available Transformasi gen superoxide dismutase (MaSOD pada rumput laut Kappaphycus alvarezii menggunakan Agrobacterium tumefacient telah dilakukan secara in vitro. Transformasi gen MaSOD ke dalam genom rumput laut diharapkan dapat mengurangi cekaman oksidatif terutama yang disebabkan oleh perubahan suhu, salinitas, dan cemaran logam di perairan. Penelitian ini bertujuan untuk regenerasi rumput laut hasil introduksi gen MaSOD dan non-transgenik pada labu kultur. Regenerasi dan perbanyakan rumput laut hasil transformasi gen MaSOD dilakukan di laboratorium pada labu kultur yang diletakkan dalam “culture chamber” yang dilengkapi dengan aerasi menggunakan media kultur yang diperkaya dengan pupuk PES, Grund, Conwy, dan SSW sebagai kontrol, salinitas 20, 25, 30, 35, dan 40 g/L, pH 4, 5, 6, 7, dan 8. Intensitas cahaya antara 500-2.000 lux dengan fotoperiode terang dan gelap 8:16; 12:12; dan 16:8. Untuk merangsang pertumbuhan eksplan dilakukan pemeliharaan dengan penambahan hormon tumbuh IAA dan BAP dengan perbandingan 1:1, 1:2, dan 2:1. Penelitian dilakukan secara bertahap. Evaluasi transgenik dilakukan menggunakan teknik PCR. Hasil penelitian memperlihatkan bahwa sintasan yang paling tinggi diperoleh menggunakan media PES (94%, salinitas 30 g/L (90%, pH 7 (96%, intensitas cahaya pada 1.500 lux (80%, fotoperiode 12:12 (84%, komposisi ZPT dengan campuran IAA dan BAP dengan perbandingan 2:1. Hasil analisis PCR memperlihatkan K. alvarezii transgenik putatif mengandung transgen MaSOD sebanyak 78% dari hasil transformasi. Superoxide dismutase transformation (MaSOD gene of seaweed Kappaphycus alvarezii mediated by Agrobacterium tumefacient has been successfully done in vitro. MaSOD genes introduced into the seaweed genome is expected to reduce oxidative stress caused by environmental conditions such as changes in temperature, salinity and metal contamination of the water. This study aimed to regenerate both the MaSOD transformed seaweed and non-transgenic in a

  20. Superoxide dismutase and taurine supplementation improves in vitro blastocyst yield from poor-quality feline oocytes.

    Science.gov (United States)

    Ochota, Małgorzata; Pasieka, Anna; Niżański, Wojciech

    2016-03-15

    Blastocyst production in vitro seems to be crucial part of assisted reproduction techniques in feline species. However, the results of cats' oocyte maturation and embryo development are still lower than those in other species. The aim of this study was to evaluate whether the supplementation with superoxide dismutase (SOD) and taurine during maturation or culture would improve the blastocyst yield obtained from lower grades of oocytes, that are usually discarded, as not suitable for further in vitro purposes. To investigate the effect of antioxidants' addition, the good- and poor-quality oocytes, were cultured with the addition of 10-mmol taurine and 600 UI/mL SOD. The nuclear maturity, embryo development, and blastocyst quality were subsequently assessed. In control group, without antioxidant supplementation, significantly less poor-quality oocytes matured (42% vs. 62%) and more degenerated (35% vs. 20%), comparing to the experimental group supplemented with SOD and taurine. The amount of obtained blastocyst was much higher, when poor quality oocytes were supplemented with SOD and taurine (supplementation to IVM-4%; supplementation to IVC-5.5%; supplementation to IVM and IVC-5.9% of blastocyst), comparing to not supplemented control group (1.3%). The best blastocysts were obtained when poor oocytes had antioxidants added only during embryo culture (185 ± 13.4 blastomeres vs. 100 ± 1.5 in control). In the present study, we reported that the lower grades of oocytes can better mature and form significantly more blastocysts with better quality, when cultured with addition of SOD and taurine. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The manganese superoxide dismutase Ala16Val dimorphism modulates iron accumulation in human hepatoma cells.

    Science.gov (United States)

    Nahon, Pierre; Charnaux, Nathalie; Friand, Véronique; Prost-Squarcioni, Catherine; Ziol, Marianne; Lièvre, Nicole; Trinchet, Jean-Claude; Beaugrand, Michel; Gattegno, Liliane; Pessayre, Dominique; Sutton, Angela

    2008-11-01

    The Ala/16Val dimorphism incorporates alanine (Ala) or valine (Val) in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD), modifying MnSOD mitochondrial import and activity. In alcoholic cirrhotic patients, the Ala-MnSOD allele is associated with hepatic iron accumulation and an increased risk of hepatocellular carcinoma. The Ala-MnSOD variant could modulate the expression of proteins involved in iron storage (cytosolic ferritin), uptake (transferrin receptors, TfR-1 and-2), extrusion (hepcidin), and intracellular distribution (frataxin) to trigger hepatic iron accumulation. We therefore assessed the Ala/Val-MnSOD genotype and the hepatic iron score in 162 alcoholic cirrhotic patients. In our cohort, this hepatic iron score increased with the number of Ala-MnSOD alleles. We also transfected Huh7 cells with Ala-MnSOD-or Val-MnSOD-encoding plasmids and assessed cellular iron, MnSOD activity, and diverse mRNAs and proteins. In Huh7 cells, MnSOD activity was higher after Ala-MnSOD transfection than after Val-MnSOD transfection. Additionally, iron supplementation decreased transfected MnSOD proteins and activities. Ala-MnSOD transfection increased the mRNAs and proteins of ferritin, hepcidin, and TfR2, decreased the expression of frataxin, and caused cellular iron accumulation. In contrast, Val-MnSOD transfection had limited effects. In conclusion, the Ala-MnSOD variant favors hepatic iron accumulation by modulating the expression of proteins involved in iron homeostasis.

  2. Copper and Zinc Metallation Status of Copper Zinc Superoxide Dismutase form Amyotrophic Lateral Sclerosis Transgenic Mice

    Energy Technology Data Exchange (ETDEWEB)

    Lelie, H.L.; Miller, L.; Liba, A.; Bourassa, M.W.; Chattopadhyay, M.; Chan, P.K.; Gralla, E.B.; Borchelt, D.R.; et al

    2010-09-24

    Mutations in the metalloenzyme copper-zinc superoxide dismutase (SOD1) cause one form of familial amyotrophic lateral sclerosis (ALS), and metals are suspected to play a pivotal role in ALS pathology. To learn more about metals in ALS, we determined the metallation states of human wild-type or mutant (G37R, G93A, and H46R/H48Q) SOD1 proteins from SOD1-ALS transgenic mice spinal cords. SOD1 was gently extracted from spinal cord and separated into insoluble (aggregated) and soluble (supernatant) fractions, and then metallation states were determined by HPLC inductively coupled plasma MS. Insoluble SOD1-rich fractions were not enriched in copper and zinc. However, the soluble mutant and WT SOD1s were highly metallated except for the metal-binding-region mutant H46R/H48Q, which did not bind any copper. Due to the stability conferred by high metallation of G37R and G93A, it is unlikely that these soluble SOD1s are prone to aggregation in vivo, supporting the hypothesis that immature nascent SOD1 is the substrate for aggregation. We also investigated the effect of SOD1 overexpression and disease on metal homeostasis in spinal cord cross-sections of SOD1-ALS mice using synchrotron-based x-ray fluorescence microscopy. In each mouse genotype, except for the H46R/H48Q mouse, we found a redistribution of copper between gray and white matters correlated to areas of high SOD1. Interestingly, a disease-specific increase of zinc was observed in the white matter for all mutant SOD1 mice. Together these data provide a picture of copper and zinc in the cell as well as highlight the importance of these metals in understanding SOD1-ALS pathology.

  3. Extracellular but not cytosolic superoxide dismutase protects against oxidant-mediated endothelial dysfunction

    Directory of Open Access Journals (Sweden)

    Erin L. Foresman

    2013-01-01

    Full Text Available Superoxide (O2•− contributes to the development of cardiovascular disease. Generation of O2•− occurs in both the intracellular and extracellular compartments. We hypothesized that the gene transfer of cytosolic superoxide dismutase (SOD1 or extracellular SOD (SOD3 to blood vessels would differentially protect against O2•−-mediated endothelial-dependent dysfunction. Aortic ring segments from New Zealand rabbits were incubated with adenovirus (Ad containing the gene for Escherichia coli β-galactosidase, SOD1, or SOD3. Activity assays confirmed functional overexpression of both SOD3 and SOD1 isoforms in aorta 24 h following gene transfer. Histochemical staining for β-galactosidase showed gene transfer occurred in the endothelium and adventitia. Next, vessels were prepared for measurement of isometric tension in Kreb's buffer containing xanthine. After precontraction with phenylephrine, xanthine oxidase impaired relaxation to the endothelium-dependent dilator acetylcholine (ACh, max relaxation 33±4% with XO vs. 64±3% without XO, p<0.05, whereas relaxation to the endothelium-independent dilator sodium nitroprusside was unaffected. In the presence of XO, maximal relaxation to ACh was improved in vessels incubated with AdSOD3 (55±2%, p<0.05 vs. control but not AdSOD1 (34±4%. We conclude that adenoviral-mediated gene transfer of SOD3, but not SOD1, protects the aorta from xanthine/XO-mediated endothelial dysfunction. These data provide important insight into the location and enzymatic source of O2•− production in vascular disease.

  4. Cu(II)-disulfide complexes display simultaneous superoxide dismutase- and catalase-like activities.

    Science.gov (United States)

    Aliaga, Margarita E; Andrade-Acuña, Daniela; López-Alarcón, Camilo; Sandoval-Acuña, Cristián; Speisky, Hernán

    2013-12-01

    Superoxide is a potentially toxic by-product of cellular metabolism. We have addressed here the in vitro ability of complexes formed between copper(II) ions and various biologically-occurring disulfides (RSSR: oxidized glutathione, cystine, homocystine and α-lipoic acid) to react with superoxide. The studied complexes were found to react with superoxide (generated by a xanthine/xanthine oxidase system) at rate constants (kCu(II)-RSSR) close to 10(6)M(-1)s(-1), which are three orders of magnitude lower than that reported for superoxide dismutase (SOD) but comparable to that of several other copper-containing complexes reported as SOD mimetics. The interaction between the tested Cu(II)-RSSR and superoxide, led to the generation and recovery of concentrations of hydrogen peroxide and oxygen that were, respectively, below and above those theoretically-expected from a sole SOD mimetic action. Interestingly, oxygen was generated when the Cu(II)-RSSR complexes were directly incubated with hydrogen peroxide. Taken together, these results reveal that the Cu(II)-RSSR complexes not only have the capacity to dismutate superoxide but also to simultaneously act like catalase mimetic molecules. When added to superoxide-overproducing mitochondria (condition attained by its exposure to diclofenac), three of the tested complexes were able (2-4μM), not only to totally restore, but also to lower below the basal level the mitochondrial production of superoxide. The present study is first in reporting on the potential of Cu(II)-disulfide complexes to act as SOD and catalase like molecules, suggesting a potential for these types of molecules to act as such under physiological and/or oxidative-stress conditions.

  5. Decreased erythrocyte superoxide dismutase in elderly men with early nuclear cataract

    Directory of Open Access Journals (Sweden)

    Rose Rose

    2015-12-01

    Full Text Available BACKGROUND Imbalance between oxidative processes and antioxidant defenses has been considered to play a role in cataractogenesis, particularly in diabetes patients. Superoxide dismutase (SOD is an important precursor for oxidative stress in the human lens, and its activity is mainly dependent on the copper and zinc levels in the body. The aim of this study was to compare erythrocyte SOD, erythrocyte zinc and total serum testosterone levels in male patients with early senile nuclear cataract and evaluate the correlations between the parameters in all subjects. METHODS A community-based study of cross-sectional design was conducted at Cilandak District Primary Health Center where 52 adult and 17 elderly men with early senile nuclear cataract were chosen as the study subjects. Erythrocyte SOD, erythrocyte zinc, serum testosterone, and fasting blood glucose (FBG levels were measured in all subjects. Nuclear cataract stage was assessed with the Pentacam® instrument (Oculus, Germany. Independent Student t test and Pearson’s correlation were used to analyze the results. RESULTS Erythrocyte SOD level was significantly decreased in elderly men compared to adult men (p=0.014. Erythrocyte zinc, serum testosterone and FBG did not differ significantly in adult and elderly males (at p=0.304; p=0.145;and p=0.376, respectively. Erythrocyte SOD activity was significantly associated with erythrocyte zinc level (r=0.486; p=0.048. CONCLUSIONS Lower erythrocyte SOD activity was found in elderly males than in adult males with early nuclear cataract. There was a relationship between erythrocyte SOD and erythrocyte zinc level in elderly males with early nuclear cataract.

  6. Evaluation of Serum Superoxide Dismutase Activity, Malondialdehyde, and Zinc and Copper Levels in Patients With Keratoconus.

    Science.gov (United States)

    Kılıç, Raşit; Bayraktar, Aslhan Cavunt; Bayraktar, Serdar; Kurt, Ali; Kavutçu, Mustafa

    2016-12-01

    The aim of this study was to evaluate the relationship between antioxidant superoxide dismutase (SOD) enzyme activity, malondialdehyde (MDA) as a lipid peroxidation marker, and some trace elements such as zinc (Zn) and copper (Cu) levels in patients with keratoconus. A total of 58 patients with keratoconus and 53 control subjects with similar age and sex were evaluated in this study. The modified Krumeich keratoconus classification was used to divide the patients into 4 stages. Serum SOD activity, MDA, and zinc and copper levels were compared between the patient and control groups. The median serum SOD activity, MDA, and Zn and Cu levels were 27.2 (42.4-13.7) U/mL, 10.2 (11.9-8.5) nmol/mL, 87.9 (104.6-76.5) μmol/L, and 103.2 (117.9-90.3) μmol/L in the keratoconus group and 26.2 (32.5-14.4) U/mL, 8.8 (11.4-7.1) nmol/mL, 100.5 (121.1-81.8) μmol/L, and 98.4 (120.3-83.4) μmol/L in the control group, respectively. There was a statistically significant difference between the MDA and Zn levels of the keratoconus group and control subjects but not between the respective SOD activities or Cu levels (P = 0.016, P = 0.031, P = 0.440, and P = 0.376, respectively). We found no significant difference between the keratoconus group stages for serum SOD activity, serum MDA, and Zn and Cu levels (P > 0.05), and there was also no significant correlation between the keratoconus group stages and serum SOD activity, serum MDA, and Zn and Cu levels (P > 0.05). There is imbalance in the systemic oxidant/antioxidant status where Zn deficiency also plays a role in patients with keratoconus.

  7. Roles of zinc and copper in modulating the oxidative refolding of bovine copper, zinc superoxide dismutase.

    Science.gov (United States)

    Li, Hong-Tao; Jiao, Ming; Chen, Jie; Liang, Yi

    2010-03-15

    The structural integrity of the ubiquitous enzyme copper, zinc superoxide dismutase (SOD1) depends critically on the correct coordination of zinc and copper. We investigate here the roles of the stoichiometric zinc and copper ions in modulating the oxidative refolding of reduced, denatured bovine erythrocyte SOD1 at physiological pH and room temperature. Fluorescence experiment results showed that the oxidative refolding of the demetalated SOD1 (apo-SOD1) is biphasic, and the addition of stoichiometric Zn(2+) into the refolding buffer remarkably accelerates both the fast phase and the slow phase of the oxidative refolding, compared with without Zn(2+). Aggregation of apo-SOD1 in the presence of stoichiometric Zn(2+) is remarkably slower than that in the absence of Zn(2+). In contrast, the effects of stoichiometric Cu(2+) on both the rates of the oxidative refolding and the aggregation of apo-SOD1 are not remarkable. Experiments of resistance to proteinase K showed that apo-SOD1 forms a conformation with low-level proteinase K resistance during refolding and stoichiometric Cu(2+) has no obvious effect on the resistance to proteinase K. In contrast, when the refolding buffer contains stoichiometric zinc, SOD1 forms a compact conformation with high-level proteinase K resistance during refolding. Our data here demonstrated that stoichiometric zinc plays an important role in the oxidative refolding of low micromolar bovine SOD1 by accelerating the oxidative refolding, suppressing the aggregation during refolding, and helping the protein to form a compact conformation with high protease resistance activity.

  8. Interdisciplinary therapy changes superoxide dismutase activity and adiponectin in obese adolescents: a randomised controlled trial.

    Science.gov (United States)

    Nunes, João Elias Dias; Cunha, Heitor Santos; Freitas, Zulmária Rezende; Nogueira, Ana Maria Caixeta; Dâmaso, Ana Raimunda; Espindola, Foued Salmen; Cheik, Nadia Carla

    2016-01-01

    The objective of this study is to evaluate the effect of interdisciplinary therapy in the parameters of the oxidative stress and the anti-inflammatory responses of obese adolescents. We selected 57 participants, who were randomly divided into 2 groups: interdisciplinary therapy group and a control group. After 6 months of intervention, 17 participants of the interdisciplinary therapy group and 8 of the control group returned for re-evaluation. The interdisciplinary therapy group participated in a treatment with 4 weekly sessions of exercise, a weekly group therapy session and a weekly nutritional education session. Blood parameters of oxidative stress and anti-inflammatory response were evaluated. The results demonstrated that there were significant increases in the interdisciplinary therapy group for superoxide dismutase activity (6.56 ± 3.22 to 11.40 ± 7.49) and ferric-reducing antioxidant potential concentration (532.91 ± 106.48 to 573.25 ± 112.57), although adiponectin levels did not reduce (40.9 ± 29.34 to 49.05 ± 41.22). A significant decrease in nitrite levels was also found (14.23 ± 8.48 to 11.45 ± 6.05). In the control group, significant reduction was found in adiponectin (31.56 ± 18.88 to 18.01 ± 11.66). This study suggests that interdisciplinary therapy for 6 months was effective in improving the anti-inflammatory responses and the antioxidant defences in obese adolescents.

  9. Mitochondrial changes in ageing Caenorhabditis elegans--what do we learn from superoxide dismutase knockouts?

    Directory of Open Access Journals (Sweden)

    Jan Gruber

    Full Text Available One of the most popular damage accumulation theories of ageing is the mitochondrial free radical theory of ageing (mFRTA. The mFRTA proposes that ageing is due to the accumulation of unrepaired oxidative damage, in particular damage to mitochondrial DNA (mtDNA. Within the mFRTA, the "vicious cycle" theory further proposes that reactive oxygen species (ROS promote mtDNA mutations, which then lead to a further increase in ROS production. Recently, data have been published on Caenorhabditis elegans mutants deficient in one or both forms of mitochondrial superoxide dismutase (SOD. Surprisingly, even double mutants, lacking both mitochondrial forms of SOD, show no reduction in lifespan. This has been interpreted as evidence against the mFRTA because it is assumed that these mutants suffer from significantly elevated oxidative damage to their mitochondria. Here, using a novel mtDNA damage assay in conjunction with related, well established damage and metabolic markers, we first investigate the age-dependent mitochondrial decline in a cohort of ageing wild-type nematodes, in particular testing the plausibility of the "vicious cycle" theory. We then apply the methods and insights gained from this investigation to a mutant strain for C. elegans that lacks both forms of mitochondrial SOD. While we show a clear age-dependent, linear increase in oxidative damage in WT nematodes, we find no evidence for autocatalytic damage amplification as proposed by the "vicious cycle" theory. Comparing the SOD mutants with wild-type animals, we further show that oxidative damage levels in the mtDNA of SOD mutants are not significantly different from those in wild-type animals, i.e. even the total loss of mitochondrial SOD did not significantly increase oxidative damage to mtDNA. Possible reasons for this unexpected result and some implications for the mFRTA are discussed.

  10. Superoxide dismutase SodB is a protective antigen against Campylobacter jejuni colonisation in chickens

    Science.gov (United States)

    Chintoan-Uta, Cosmin; Cassady-Cain, Robin L.; Al-Haideri, Halah; Watson, Eleanor; Kelly, David J.; Smith, David G.E.; Sparks, Nick H.C.; Kaiser, Pete; Stevens, Mark P.

    2015-01-01

    Campylobacter is the leading cause of foodborne diarrhoeal illness in the developed world and consumption or handling of contaminated poultry meat is the principal source of infection. Strategies to control Campylobacter in broilers prior to slaughter are urgently required and are predicted to limit the incidence of human campylobacteriosis. Towards this aim, a purified recombinant subunit vaccine based on the superoxide dismutase (SodB) protein of C. jejuni M1 was developed and tested in White Leghorn birds. Birds were vaccinated on the day of hatch and 14 days later with SodB fused to glutathione S-transferase (GST) or purified GST alone. Birds were challenged with C. jejuni M1 at 28 days of age and caecal Campylobacter counts determined at weekly intervals. Across three independent trials, the vaccine induced a statistically significant 1 log10 reduction in caecal Campylobacter numbers in vaccinated birds compared to age-matched GST-vaccinated controls. Significant induction of antigen-specific serum IgY was detected in all vaccinated birds, however the magnitude and timing of SodB-specific IgY did not correlate with lower numbers of C. jejuni. Antibodies from SodB-vaccinated chickens detected the protein in the periplasm and not membrane fractions or on the bacterial surface, suggesting that the protection observed may not be strictly antibody-mediated. SodB may be useful as a constituent of vaccines for control of C. jejuni infection in broiler birds, however modest protection was observed late relative to the life of broiler birds and further studies are required to potentiate the magnitude and timing of protection. PMID:26458797

  11. Peroxisomal membrane manganese superoxide dismutase: characterization of the isozyme from watermelon (Citrullus lanatus Schrad.) cotyledons.

    Science.gov (United States)

    Rodríguez-Serrano, María; Romero-Puertas, María C; Pastori, Gabriela M; Corpas, Francisco J; Sandalio, Luisa M; del Río, Luis A; Palma, José M

    2007-01-01

    In this work the manganese superoxide dismutase (Mn-SOD) bound to peroxisomal membranes of watermelon cotyledons (Citrullus lanatus Schrad.) was purified to homogeneity and some of its molecular properties were determined. The stepwise purification procedure consisted of ammonium sulphate fractionation, batch anion-exchange chromatography, and anion-exchange and gel-filtration column chromatography using a fast protein liquid chromatography system. Peroxisomal membrane Mn-SOD (perMn-SOD; EC 1.15.1.1) was purified 5600-fold with a yield of 2.6 mug of enzyme g(-1) of cotyledons, and had a specific activity of 480 U mg(-1) of protein. The native molecular mass determined for perMn-SOD was 108 000 Da, and it was composed of four equal subunits of 27 kDa, which indicates that perMn-SOD is a homotetramer. Ultraviolet and visible absorption spectra of the enzyme showed a shoulder at 275 nm and two absorption maxima at 448 nm and 555 nm, respectively. By isoelectric focusing, a pI of 5.75 was determined for perMn-SOD. In immunoblot assays, purified perMn-SOD was recognized by a polyclonal antibody against Mn-SOD from pea leaves, and the peroxisomal enzyme rapidly dissociated in the presence of dithiothreitol and SDS. The potential binding of the Mn-SOD isozyme to the peroxisomal membrane was confirmed by immunoelectron microscopy analysis. The properties of perMn-SOD and the mitMn-SOD are compared and the possible function in peroxisomal membranes of the peripheral protein Mn-SOD is discussed.

  12. LC-MS/MS Analysis Unravels Deep Oxidation of Manganese Superoxide Dismutase in Kidney Cancer

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    Zuohui Zhao

    2017-02-01

    Full Text Available Manganese superoxide dismutase (MNSOD is one of the major scavengers of reactive oxygen species (ROS in mitochondria with pivotal regulatory role in ischemic disorders, inflammation and cancer. Here we report oxidative modification of MNSOD in human renal cell carcinoma (RCC by the shotgun method using data-dependent liquid chromatography tandem mass spectrometry (LC-MS/MS. While 5816 and 5571 proteins were identified in cancer and adjacent tissues, respectively, 208 proteins were found to be up- or down-regulated (p < 0.05. Ontological category, interaction network and Western blotting suggested a close correlation between RCC-mediated proteins and oxidoreductases such as MNSOD. Markedly, oxidative modifications of MNSOD were identified at histidine (H54 and H55, tyrosine (Y58, tryptophan (W147, W149, W205 and W210 and asparagine (N206 and N209 residues additional to methionine. These oxidative insults were located at three hotspots near the hydrophobic pocket of the manganese binding site, of which the oxidation of Y58, W147 and W149 was up-regulated around three folds and the oxidation of H54 and H55 was detected in the cancer tissues only (p < 0.05. When normalized to MNSOD expression levels, relative MNSOD enzymatic activity was decreased in cancer tissues, suggesting impairment of MNSOD enzymatic activity in kidney cancer due to modifications. Thus, LC-MS/MS analysis revealed multiple oxidative modifications of MNSOD at different amino acid residues that might mediate the regulation of the superoxide radicals, mitochondrial ROS scavenging and MNSOD activity in kidney cancer.

  13. Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yani [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Leu, David [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Palo Alto Institute of Research and Education, Palo Alto, California (United States); Chui, Jennifer [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Fike, John R. [Departments of Neurosurgery and Radiation Oncology, University of California, San Francisco, California (United States); Huang, Ting-Ting, E-mail: tthuang@stanford.edu [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); VA Palo Alto Health Care System, Palo Alto, California (United States)

    2013-11-15

    Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted.

  14. Superoxide dismutase SodB is a protective antigen against Campylobacter jejuni colonisation in chickens.

    Science.gov (United States)

    Chintoan-Uta, Cosmin; Cassady-Cain, Robin L; Al-Haideri, Halah; Watson, Eleanor; Kelly, David J; Smith, David G E; Sparks, Nick H C; Kaiser, Pete; Stevens, Mark P

    2015-11-17

    Campylobacter is the leading cause of foodborne diarrhoeal illness in the developed world and consumption or handling of contaminated poultry meat is the principal source of infection. Strategies to control Campylobacter in broilers prior to slaughter are urgently required and are predicted to limit the incidence of human campylobacteriosis. Towards this aim, a purified recombinant subunit vaccine based on the superoxide dismutase (SodB) protein of C. jejuni M1 was developed and tested in White Leghorn birds. Birds were vaccinated on the day of hatch and 14 days later with SodB fused to glutathione S-transferase (GST) or purified GST alone. Birds were challenged with C. jejuni M1 at 28 days of age and caecal Campylobacter counts determined at weekly intervals. Across three independent trials, the vaccine induced a statistically significant 1 log10 reduction in caecal Campylobacter numbers in vaccinated birds compared to age-matched GST-vaccinated controls. Significant induction of antigen-specific serum IgY was detected in all vaccinated birds, however the magnitude and timing of SodB-specific IgY did not correlate with lower numbers of C. jejuni. Antibodies from SodB-vaccinated chickens detected the protein in the periplasm and not membrane fractions or on the bacterial surface, suggesting that the protection observed may not be strictly antibody-mediated. SodB may be useful as a constituent of vaccines for control of C. jejuni infection in broiler birds, however modest protection was observed late relative to the life of broiler birds and further studies are required to potentiate the magnitude and timing of protection.

  15. Species and Organ Diversity in the Effects of Hydrogen Peroxide on Superoxide Dismutase Activity In Vitro

    Institute of Scientific and Technical Information of China (English)

    Hong-Yan Cheng; Song-Quan Song

    2006-01-01

    Superoxide dismutase (SOD) is ubiquitous in aerobic organisms and constitutes the first link in the enzyme scavenging system of reactive oxygen species. In the present study, species and organ diversity of SOD activity in a solution and in an in-gel assay system, as well as the effects of hydrogen peroxide (H2O2) on SOD activity, were investigated. In a solution assay system, SOD activity of jackfruit root, shoot, leaves, axes, and cotyledons, of maize embryos and endosperms, of mung bean leaves and seeds, of sacred lotus axes and cotyledons, and of rice and wheat leaves was increased by 1-15 mmol/L H2O2. However, SOD activity in rice root and seeds, maize roots and leaves, mung bean roots and shoots, and wheat seeds was decreased by 1-15 mmol/L H2O2. The SOD activity of wheat root and soybean roots, leaves, axes, and cotyledons was increased by 1-4 mmol/L H2O2, but was decreased by concentrations of H2O2 >4 mmol/L. The SOD activity of soybean shoots was not affected by 1-15 mmol/L H2O2. The SOD activity in crude mitochondria of jackfruit,maize, and upas seeds, as well as in purified mitochondria of jackfruit, was also increased by 1-15 mmol/L H2O2. In the in-gel assay system, the SOD in jackfruit cotyledons was comprised of Mn-SOD, Cu/Zn-SOD, and Fe-SOD, the crude mitochondria of jackfruit seeds and maizes embryo was comprised of Mn-SOD and Cu/Zn-SOD, and the crude mitochondria of maize seeds was comprised of Mn-SOD only. In the present study,H2O2 markedly inhibited Cu/Zn-SOD and Fe-SOD activity.

  16. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans.

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    Jeremy M Van Raamsdonk

    2009-02-01

    Full Text Available The oxidative stress theory of aging postulates that aging results from the accumulation of molecular damage caused by reactive oxygen species (ROS generated during normal metabolism. Superoxide dismutases (SODs counteract this process by detoxifying superoxide. It has previously been shown that elimination of either cytoplasmic or mitochondrial SOD in yeast, flies, and mice results in decreased lifespan. In this experiment, we examine the effect of eliminating each of the five individual sod genes present in Caenorhabditis elegans. In contrast to what is observed in other model organisms, none of the sod deletion mutants shows decreased lifespan compared to wild-type worms, despite a clear increase in sensitivity to paraquat- and juglone-induced oxidative stress. In fact, even mutants lacking combinations of two or three sod genes survive at least as long as wild-type worms. Examination of gene expression in these mutants reveals mild compensatory up-regulation of other sod genes. Interestingly, we find that sod-2 mutants are long-lived despite a significant increase in oxidatively damaged proteins. Testing the effect of sod-2 deletion on known pathways of lifespan extension reveals a clear interaction with genes that affect mitochondrial function: sod-2 deletion markedly increases lifespan in clk-1 worms while clearly decreasing the lifespan of isp-1 worms. Combined with the mitochondrial localization of SOD-2 and the fact that sod-2 mutant worms exhibit phenotypes that are characteristic of long-lived mitochondrial mutants-including slow development, low brood size, and slow defecation-this suggests that deletion of sod-2 extends lifespan through a similar mechanism. This conclusion is supported by our demonstration of decreased oxygen consumption in sod-2 mutant worms. Overall, we show that increased oxidative stress caused by deletion of sod genes does not result in decreased lifespan in C. elegans and that deletion of sod-2 extends worm

  17. Cloning and constitutive expression of Deschampsia antarctica Cu/Zn superoxide dismutase in Pichia pastoris

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    Gidekel Manuel

    2009-10-01

    Full Text Available Abstract Background Deschampsia antarctica shows tolerance to extreme environmental factors such as low temperature, high light intensity and an increasing UV radiation as result of the Antarctic ozone layer thinning. It is very likely that the survival of this species is due to the expression of genes that enable it to tolerate high levels of oxidative stress. On that account, we planned to clone the D. antarctica Cu/ZnSOD gene into Pichia pastoris and to characterize the heterologous protein. Findings The Copper/Zinc superoxide dismutase (Cu/ZnSOD gene, SOD gene, was isolated from a D. antarctica by cDNA library screening. This SOD gene was cloned in the expression vector pGAPZαA and successfully integrated into the genome of the yeast P. pastoris SMD1168H. A constitutive expression system for the expression of the recombinant SOD protein was used. The recombinant protein was secreted into the YPD culture medium as a glycosylated protein with a 32 mg/l expression yield. The purified recombinant protein possesses a specific activity of 440 U/mg. Conclusion D. antarctica Cu/ZnSOD recombinant protein was expressed in a constitutive system, and purified in a single step by means of an affinity column. The recombinant SOD was secreted to the culture medium as a glycoprotein, corresponding to approximately 13% of the total secreted protein. The recombinant protein Cu/ZnSOD maintains 60% of its activity after incubation at 40°C for 30 minutes and it is stable (80% of activity between -20°C and 20°C. The recombinant SOD described in this study can be used in various biotechnological applications.

  18. Comparative evaluation of serum superoxide dismutase and glutathione levels in periodontally diseased patients: An interventional study

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    Thomas Biju

    2014-01-01

    Full Text Available Background: Periodontal disease is an immune-inflammatory disease characterized by connective tissue breakdown, loss of attachment, and alveolar bone resorption. Under normal physiological conditions, a dynamic equilibrium is maintained between the reactive oxygen species (ROS and antioxidant defense capacity. Oxidative stress occurs when this equilibrium shifts in favor of ROS. Oxidative stress is thought to play a causative role in the pathogenesis of periodontal diseases. Aim: The present study was designed to estimate and compare the superoxide dismutase (SOD and glutathione (GSH levels in the serum of periodontitis, gingivitis, and healthy individuals before and after nonsurgical periodontal therapy. Materials and Methods: The present study was conducted in the Department of Periodontics, A. B. Shetty Memorial Institute of Dental Sciences, Deralakatte, Mangalore. The study was designed as a single blinded interventional study comprising 75 subjects, inclusive of both sexes and divided into three groups of 25 patients each. Patients were categorized into chronic periodontitis, gingivitis, and healthy. The severity of inflammation was assessed using gingival index and pocket probing depth. Biochemical analysis was done to estimate the SOD and GSH levels before and after nonsurgical periodontal therapy. Results obtained were then statistically analyzed using ANOVA test and paired t-test. Results: The results showed a higher level of serum SOD and GSH in the healthy group compared to the other groups. The difference was found to be statistically significant (P < 0.0001. The post-treatment levels of SOD were statistically higher than the pre-treatment levels in periodontitis and gingivitis group.

  19. The Effect of UV-B Radiation on Bufo arenarum Embryos Survival and Superoxide Dismutase Activity

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    O. Fridman

    2006-03-01

    Full Text Available The exposure of Bufo arenarum embryos to 300-310 nm UV-B at a dose of 4,104 Joule/m2 resulted in 100% lethality within 24 hr while 820 Joule/m2 was the NOEC value for short-term chronic (10 days exposure. The dose response curves show that lethal effects are proportional with the dose and achieve its highest value within 48 hr post exposure. The superoxide dismutase (SOD activity in amphibian embryos for sublethal UV-B exposures was evaluated by means of UV-B treatments with 273 (A, 820(B, 1368(C and 1915(D Joule/m2 at 2 and 5 hours post irradiation. The SOD activity in units/mg protein in A, B, C and D at 2 hr after treatments were 80.72 ± 14.29, 74.5 ± 13.19, 39.5 ± 6.99 and 10.7 ± 1.89 respectively while for control embryos it was 10.88 ± 1.31. At 5 hr after treatments the SOD values were similar to those found in control embryos. The results confirm the high susceptibility of amphibian embryos to UV-B and point out that the SOD activity is enhanced by low doses of UV-B irradiation achieving significantly higher values than in control embryos at 2 hr post exposure.

  20. The role of a cytosolic superoxide dismutase in barley-pathogen interactions

    KAUST Repository

    Lightfoot, Damien J.

    2016-03-19

    Reactive oxygen species (ROS), including superoxide (O2-HO2) and hydrogen peroxide (H2O2), are differentially produced during resistance responses to biotrophic pathogens and during susceptible responses to necrotrophic and hemi-biotrophic pathogens. Superoxide dismutase (SOD) is responsible for the catalysis of the dismutation of O2-HO2 to H2O2, regulating the redox status of plant cells. Increased SOD activity has been correlated previously with resistance in barley to the hemi-biotrophic pathogen Pyrenophora teres f. teres (Ptt, the causal agent of the net form of net blotch disease), but the role of individual isoforms of SOD has not been studied. A cytosolic CuZnSOD, HvCSD1, was isolated from barley and characterized as being expressed in tissue from different developmental stages. HvCSD1 was up-regulated during the interaction with Ptt and to a greater extent during the resistance response. Net blotch disease symptoms and fungal growth were not as pronounced in transgenic HvCSD1 knockdown lines in a susceptible background (cv. Golden Promise), when compared with wild-type plants, suggesting that cytosolic O2-HO2 contributes to the signalling required to induce a defence response to Ptt. There was no effect of HvCSD1 knockdown on infection by the hemi-biotrophic rice blast pathogen Magnaporthe oryzae or the biotrophic powdery mildew pathogen Blumeria graminis f. sp. hordei, but HvCSD1 also played a role in the regulation of lesion development by methyl viologen. Together, these results suggest that HvCSD1 could be important in the maintenance of the cytosolic redox status and in the differential regulation of responses to pathogens with different lifestyles.

  1. Age-associated intracellular superoxide dismutase deficiency potentiates dermal fibroblast dysfunction during wound healing.

    Science.gov (United States)

    Fujiwara, Toshihiro; Dohi, Teruyuki; Maan, Zeshaan N; Rustad, Kristine C; Kwon, Sun Hyung; Padmanabhan, Jagannath; Whittam, Alexander J; Suga, Hirotaka; Duscher, Dominik; Rodrigues, Melanie; Gurtner, Geoffrey C

    2017-07-04

    Reactive oxygen species (ROS) impair wound healing through destructive oxidation of intracellular proteins, lipids and nucleic acids. Intracellular superoxide dismutase (SOD1) regulates ROS levels and plays a critical role in tissue homoeostasis. Recent evidence suggests that age-associated wound healing impairments may partially result from decreased SOD1 expression. We investigated the mechanistic basis by which increased oxidative stress links to age-associated impaired wound healing. Fibroblasts were isolated from unwounded skin of young and aged mice, and myofibroblast differentiation was assessed by measuring α-smooth muscle actin and collagen gel contraction. Excisional wounds were created on young and aged mice to study the healing rate, ROS levels and SOD1 expression. A mechanistic link between oxidative stress and fibroblast function was explored by assessing the TGF-β1 signalling pathway components in young and aged mice. Age-related wounds displayed reduced myofibroblast differentiation and delayed wound healing, consistent with a decrease in the in vitro capacity for fibroblast-myofibroblast transition following oxidative stress. Young fibroblasts with normal SOD1 expression exhibited increased phosphorylation of ERK in response to elevated ROS. In contrast, aged fibroblasts with reduced SOD1 expression displayed a reduced capacity to modulate intracellular ROS. Collectively, age-associated wound healing impairments are associated with fibroblast dysfunction that is likely the result of decreased SOD1 expression and subsequent dysregulation of intracellular ROS. Strategies targeting these mechanisms may suggest a new therapeutic approach in the treatment of chronic non-healing wounds in the aged population. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Superoxide dismutase isozyme detection using two-dimensional gel electrophoresis zymograms.

    Science.gov (United States)

    Niyomploy, Ploypat; Srisomsap, Chantragan; Chokchaichamnankit, Daranee; Vinayavekhin, Nawaporn; Karnchanatat, Aphichart; Sangvanich, Polkit

    2014-03-01

    Superoxide dismutases (SODs) are ubiquitous antioxidant enzymes involved in cell protection from reactive oxygen species. Their antioxidant activities make them of interest to applied biotechnology industries and are usually sourced from plants. SODs are also involved in stress signaling responses in plants, and can be used as indicators of these responses. In this article, a suitable method for the separation of different SOD isoforms using two-dimensional-gel electrophoresis (2D-GE) zymograms is reported. The method was developed with a SOD standard from bovine erythrocytes and later applied to extracts from Stemona tuberosa. The first (non-denaturing isoelectric focusing) and second (denaturing sodium dodecylsulphate-polyacrylamide gel electrophoresis) dimensions of duplicate 2D-GE gels were stained with either Coomassie brilliant blue G-250 for total protein visualization, or SOD activity (zymogram) using riboflavin/nitroblue tetrazolium. For confirmation, putative SOD activity positive spots were subject to trypsin digestion and nano-liquid chromatography tandem mass spectrometry, followed by searching the MASCOT database for potential identification. The method could separate different SOD isoforms from a plant extract and at least partially maintain or allow renaturation to the native forms of the enzyme. Peptide sequencing of the 2D-GE suggested that the SODs were resolved correctly, identifying the control CuZn-SOD from bovine erythrocytes. The two SODs from S. tuberosa tubers were found to be likely homologous of a CuZn-SOD. SOD detection and isoform separation by 2D-GE zymograms was efficient and reliable. The method is likely applicable to SOD detection from plants or other organisms. Moreover, a similar approach could be developed for detection of other important enzymes in the future. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  4. Isolation and in silico analysis of Fe-superoxide dismutase in the cyanobacterium Nostoc commune.

    Science.gov (United States)

    Kesheri, Minu; Kanchan, Swarna; Richa; Sinha, Rajeshwar P

    2014-12-15

    Cyanobacteria are known to endure various stress conditions due to the inbuilt potential for oxidative stress alleviation owing to the presence of an array of antioxidants. The present study shows that Antarctic cyanobacterium Nostoc commune possesses two antioxidative enzymes viz., superoxide dismutase (SOD) and catalase that jointly cope with environmental stresses prevailing at its natural habitat. Native-PAGE analysis illustrates the presence of a single prominent isoform recognized as Fe-SOD and three distinct isoforms of catalase. The protein sequence of Fe-SOD in N. commune retrieved from NCBI protein sequence database was used for in silico analysis. 3D structure of N. commune was predicted by comparative modeling using MODELLER 9v11. Further, this model was validated for its quality by Ramachandran plot, ERRAT, Verify 3D and ProSA-web which revealed good structure quality of the model. Multiple sequence alignment showed high conservation in N and C-terminal domain regions along with all metal binding positions in Fe-SOD which were also found to be highly conserved in all 28 cyanobacterial species under study, including N. commune. In silico prediction of isoelectric point and molecular weight of Fe-SOD was found to be 5.48 and 22,342.98Da respectively. The phylogenetic tree revealed that among 28 cyanobacterial species, Fe-SOD in N. commune was the closest evolutionary homolog of Fe-SOD in Nostoc punctiforme as evident by strong bootstrap value. Thus, N. commune may serve as a good biological model for studies related to survival of life under extreme conditions prevailing at the Antarctic region. Moreover cyanobacteria may be exploited for biochemical and biotechnological applications of enzymatic antioxidants. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Mitochondrial changes in ageing Caenorhabditis elegans--what do we learn from superoxide dismutase knockouts?

    Science.gov (United States)

    Gruber, Jan; Ng, Li Fang; Fong, Sheng; Wong, Yee Ting; Koh, Soon Ann; Chen, Ce-Belle; Shui, Guanghou; Cheong, Wei Fun; Schaffer, Sebastian; Wenk, Markus R; Halliwell, Barry

    2011-01-01

    One of the most popular damage accumulation theories of ageing is the mitochondrial free radical theory of ageing (mFRTA). The mFRTA proposes that ageing is due to the accumulation of unrepaired oxidative damage, in particular damage to mitochondrial DNA (mtDNA). Within the mFRTA, the "vicious cycle" theory further proposes that reactive oxygen species (ROS) promote mtDNA mutations, which then lead to a further increase in ROS production. Recently, data have been published on Caenorhabditis elegans mutants deficient in one or both forms of mitochondrial superoxide dismutase (SOD). Surprisingly, even double mutants, lacking both mitochondrial forms of SOD, show no reduction in lifespan. This has been interpreted as evidence against the mFRTA because it is assumed that these mutants suffer from significantly elevated oxidative damage to their mitochondria. Here, using a novel mtDNA damage assay in conjunction with related, well established damage and metabolic markers, we first investigate the age-dependent mitochondrial decline in a cohort of ageing wild-type nematodes, in particular testing the plausibility of the "vicious cycle" theory. We then apply the methods and insights gained from this investigation to a mutant strain for C. elegans that lacks both forms of mitochondrial SOD. While we show a clear age-dependent, linear increase in oxidative damage in WT nematodes, we find no evidence for autocatalytic damage amplification as proposed by the "vicious cycle" theory. Comparing the SOD mutants with wild-type animals, we further show that oxidative damage levels in the mtDNA of SOD mutants are not significantly different from those in wild-type animals, i.e. even the total loss of mitochondrial SOD did not significantly increase oxidative damage to mtDNA. Possible reasons for this unexpected result and some implications for the mFRTA are discussed.

  6. Cardiovascular effects of copper deficiency on activity of superoxide dismutase in diabetic nephropathy

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    Mohammed A Al-Bayati

    2015-01-01

    Full Text Available Background: Copper (Cu is essential both for its role in antioxidant enzymes, like Cu/zinc (Zn superoxide dismutase (SOD and ceruloplasmin, as well as its role in lysyl oxidase, essential for the strength and integrity of the heart and blood vessels. With such a central role in cardiovascular health, Cu has been generally overlooked in the debate over improving our cardiovascular health. Cu deficiency has produced many of the same abnormalities present in cardiovascular disease. It seems almost certain that Cu plays a large role in the development of this killer disease, not because of its excess in the diet, but rather its deficiency. Aim: This study was undertaken to investigate the cardiovascular effects of Cu deficiency on the activity of SOD in patients with type 2 diabetes mellitus (T2DM with and without diabetic nephropathy. Materials and Methods: Fifty-five patients with T2DM were recruited in this study which were divided into two subgroups based on the presence of microalbuminuria, the first group (microal buminuric group, n = 31 had a microalbuminuria between 30 and 299 μg/mg. The second group (normoal buminuric group, n = 29 had an albumin level less than 30 μg/mg. The two diabetic groups were compared to the control group (n = 37. Results: The results of our study showed a significant reduction in the levels of SOD enzyme associated with an increased urinary Cu excretion in microalbuminuric group compared to the control group at P < 0.05. Conclusions: The current study illustrates that the regulation of the blood concentrations of Cu may be a potential therapeutic target for prevention and treatment of diabetic nephropathy.

  7. Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus

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    Brenner Benjamin

    2009-10-01

    Full Text Available Abstract Background The function of endothelial progenitor cells (EPCs, which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD, the enzyme that neutralizes superoxide anion (O2-. Therefore, we investigated the roles of NO and SOD in glucose-stressed EPCs. Methods The functions of circulating EPCs from patients with type 2 diabetes were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2- generation, NO production, SOD activity, and their ability to form colonies. Results EPCs from diabetic patients generated more O2-, had higher NAD(PH oxidase and SOD activity, but lower NO bioavailability, and expressed higher mRNA and protein levels of p22-phox, and manganese SOD and copper/zinc SOD than those from the healthy individuals. Plasma glucose and HbA1c levels in the diabetic patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2- generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O2- generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment. Conclusion Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 diabetic patients.

  8. Mutations by near-ultraviolet radiation in Escherichia coli strains lacking superoxide dismutase

    Energy Technology Data Exchange (ETDEWEB)

    Hoerter, J. (Stephens College, Columbia (USA). Department of Natural Sciences); Eisenstark, A. (Missouri Univ., Columbia, MO (USA). Div. of Biological Sciences Paris 7 Universite (France). Centre National de la Recherche, Institut Jacques Monod); Touati, D. (Paris 7 Universite (France). Centre National de la Recherche, Institut Jacques Monod)

    1989-12-01

    In wild-type Eschericia coli, near-ultraviolet radiation (NUV) was only weakly mutagenic. However, in an allelic mutant strain (sodA sodB) that lacks both Mn- and Fe-superoxide dismutase (SOD) and assumed to have excess superoxide anion, NUV induced a 9-fold increase in mutatin above the level that normally occurs in this double mutant. When a sodA sodB double mutant contained a plasmid carrying katG{sup +} (excess HP-I catalase), mutation by NUV was reduced to wild-type (sodA{sup +} sodB{sup +}) levels. Also, in the sodA sodB xthA triple mutant, which lacks exonuclease III (exoIII) in addition to SOD, the mutational frequency by NUV was reduced to wild-type levels. This synergistic action of NUV and O{sub 2}{sup {minus}} suggested that pre-mutational lesions occur, with exoIII converting these lesions to stable mutants. Exposure to H{sub 2}O{sub 2} induced a 2.8-fold increase in mutations in sodA sodB double mutants, but was reduced to control levels when a plasmid carrying katG{sup +} was introduced. These results suggest that NUV, in addition to its other effects on cells, increases mutations indirectly by increasing the flux of OH{sup .} radicals, possibly by generating excess H{sub 2}O{sub 2}. (author). 20 refs.; 1 fig.; 1 tab.

  9. Cu,Zn-superoxide dismutase without Zn is folded but catalytically inactive.

    Science.gov (United States)

    Nedd, Sean; Redler, Rachel L; Proctor, Elizabeth A; Dokholyan, Nikolay V; Alexandrova, Anastassia N

    2014-12-12

    Amyotrophic lateral sclerosis has been linked to the gain of aberrant function of superoxide dismutase, Cu,Zn-SOD1 upon protein misfolding. The mechanism of SOD1 misfolding is thought to involve mutations leading to the loss of Zn, followed by protein unfolding and aggregation. We show that the removal of Zn from SOD1 may not lead to an immediate unfolding but immediately deactivates the enzyme through a combination of subtle structural and electronic effects. Using quantum mechanics/discrete molecular dynamics, we showed that both Zn-less wild-type (WT)-SOD1 and its D124N mutant that does not bind Zn have at least metastable folded states. In those states, the reduction potential of Cu increases, leading to the presence of detectable amounts of Cu(I) instead of Cu(II) in the active site, as confirmed experimentally. The Cu(I) protein cannot participate in the catalytic Cu(I)-Cu(II) cycle. However, even without the full reduction to Cu(I), the Cu site in the Zn-less variants of SOD1 is shown to be catalytically incompetent: unable to bind superoxide in a way comparable to the WT-SOD1. The changes are more radical and different in the D124N Zn-less mutant than in the Zn-less WT-SOD1, suggesting D124N being perhaps not the most adequate model for Zn-less SOD1. Overall, Zn in SOD1 appears to be influencing the Cu site directly by adjusting its reduction potential and geometry. Thus, the role of Zn in SOD1 is not just structural, as was previously thought; it is a vital part of the catalytic machinery.

  10. Response of Superoxide Dismutase, Catalase, and ATPase Activity in Bacteria Exposed to Acetamiprid

    Institute of Scientific and Technical Information of China (English)

    XIAO-HUA YAO; HANG MIN; ZHEN-MEI LV

    2006-01-01

    To investigate how acetamiprid, a new insecticide, affects the activity of superoxide dismutase (SOD),catalase (CAT), and ATPase and the SOD isozyme patterns in two G- bacteria, E. coli K12 and Pse. FH2, and one G+ bacterum,B. subtilis. Methods The SOD, CAT, and ATPase specific activities of cell lysates were determined spectrophotometrically at 550 nm, 240 nm, and 660 nm, respectively, with kits A001, A016, and A007. SOD isozyme patterns were detected by native PAGE analysis. Results SOD and CAT activities in the tested bacteria increased significantly in a concentration-dependent manner after different concentrations of acetamiprid were applied. The activity of SOD in B. subtilis and Pse. FH2 was stimulated and reached the highest level after treatment with 100 mg/L acetamiprid for 0.5 h. For Pse. FH2, there was another stimulation of SOD activity after acetamiprid application for about 8.0 h and the second stimulation was stronger than the first.The stimulation by acetamiprid showed a relative lag for E. coli K12. Acetamiprid seemed to exhibit a similar effect on CAT activity of the two G- bacteria and had an evident influence on ATPase activity in the three bacteria within a relatively short period. Only one SOD isozyme was detectable in Pse. FH2 and B. subtilis, while different isozyme compositions in E. coli could be detected by native PAGE analysis. Conclusion Acetamiprid causes a certain oxidative stress on the three bacteria which may not only elevate SOD and CAT activities but also generate new SOD isozymes to antagonize oxidative stress.However, this oxidative stress lasts for a relatively short time and does not cause a long-term damage.

  11. Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes.

    Science.gov (United States)

    Dasmeh, Pouria; Kepp, Kasper P

    2017-08-01

    Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein's evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million years, significantly higher than in other primates and rodents, although these paradoxically generally evolve much faster. The high evolutionary rate was partly due to relaxation of some selection pressures and partly to distinct positive selection of SOD1 in great apes. We then show that higher stability and net charge and changes at the dimer interface were selectively introduced upon separation from old world monkeys and lesser apes (gibbons). Consequently, human, chimpanzee and gorilla SOD1s have a net charge of -6 at physiological pH, whereas the closely related gibbons and macaques have -3. These features consistently point towards selection against the malicious aggregation effects of elevated SOD1 levels in long-living great apes. The findings mirror the impact of human SOD1 mutations that reduce net charge and/or stability and cause ALS, a motor neuron disease characterized by oxidative stress and SOD1 aggregates and triggered by aging. Our study thus marks an example of direct selection for a particular chemical phenotype (high net charge and stability) in a single human protein with possible implications for the evolution of aging.

  12. A Manganese-rich Environment Supports Superoxide Dismutase Activity in a Lyme Disease Pathogen, Borrelia burgdorferi*

    Science.gov (United States)

    Aguirre, J. Dafhne; Clark, Hillary M.; McIlvin, Matthew; Vazquez, Christine; Palmere, Shaina L.; Grab, Dennis J.; Seshu, J.; Hart, P. John; Saito, Mak; Culotta, Valeria C.

    2013-01-01

    The Lyme disease pathogen Borrelia burgdorferi represents a novel organism in which to study metalloprotein biology in that this spirochete has uniquely evolved with no requirement for iron. Not only is iron low, but we show here that B. burgdorferi has the capacity to accumulate remarkably high levels of manganese. This high manganese is necessary to activate the SodA superoxide dismutase (SOD) essential for virulence. Using a metalloproteomic approach, we demonstrate that a bulk of B. burgdorferi SodA directly associates with manganese, and a smaller pool of inactive enzyme accumulates as apoprotein. Other metalloproteins may have similarly adapted to using manganese as co-factor, including the BB0366 aminopeptidase. Whereas B. burgdorferi SodA has evolved in a manganese-rich, iron-poor environment, the opposite is true for Mn-SODs of organisms such as Escherichia coli and bakers' yeast. These Mn-SODs still capture manganese in an iron-rich cell, and we tested whether the same is true for Borrelia SodA. When expressed in the iron-rich mitochondria of Saccharomyces cerevisiae, B. burgdorferi SodA was inactive. Activity was only possible when cells accumulated extremely high levels of manganese that exceeded cellular iron. Moreover, there was no evidence for iron inactivation of the SOD. B. burgdorferi SodA shows strong overall homology with other members of the Mn-SOD family, but computer-assisted modeling revealed some unusual features of the hydrogen bonding network near the enzyme's active site. The unique properties of B. burgdorferi SodA may represent adaptation to expression in the manganese-rich and iron-poor environment of the spirochete. PMID:23376276

  13. A manganese-rich environment supports superoxide dismutase activity in a Lyme disease pathogen, Borrelia burgdorferi.

    Science.gov (United States)

    Aguirre, J Dafhne; Clark, Hillary M; McIlvin, Matthew; Vazquez, Christine; Palmere, Shaina L; Grab, Dennis J; Seshu, J; Hart, P John; Saito, Mak; Culotta, Valeria C

    2013-03-22

    The Lyme disease pathogen Borrelia burgdorferi represents a novel organism in which to study metalloprotein biology in that this spirochete has uniquely evolved with no requirement for iron. Not only is iron low, but we show here that B. burgdorferi has the capacity to accumulate remarkably high levels of manganese. This high manganese is necessary to activate the SodA superoxide dismutase (SOD) essential for virulence. Using a metalloproteomic approach, we demonstrate that a bulk of B. burgdorferi SodA directly associates with manganese, and a smaller pool of inactive enzyme accumulates as apoprotein. Other metalloproteins may have similarly adapted to using manganese as co-factor, including the BB0366 aminopeptidase. Whereas B. burgdorferi SodA has evolved in a manganese-rich, iron-poor environment, the opposite is true for Mn-SODs of organisms such as Escherichia coli and bakers' yeast. These Mn-SODs still capture manganese in an iron-rich cell, and we tested whether the same is true for Borrelia SodA. When expressed in the iron-rich mitochondria of Saccharomyces cerevisiae, B. burgdorferi SodA was inactive. Activity was only possible when cells accumulated extremely high levels of manganese that exceeded cellular iron. Moreover, there was no evidence for iron inactivation of the SOD. B. burgdorferi SodA shows strong overall homology with other members of the Mn-SOD family, but computer-assisted modeling revealed some unusual features of the hydrogen bonding network near the enzyme's active site. The unique properties of B. burgdorferi SodA may represent adaptation to expression in the manganese-rich and iron-poor environment of the spirochete.

  14. Inducible superoxide dismutase 1 aggregation in transgenic amyotrophic lateral sclerosis mouse fibroblasts.

    Science.gov (United States)

    Turner, Bradley J; Lopes, Elizabeth C; Cheema, Surindar S

    2004-04-01

    High molecular weight detergent-insoluble complexes of superoxide dismutase 1 (SOD1) enzyme are a biochemical abnormality associated with mutant SOD1-linked familial amyotrophic lateral sclerosis (FALS). In the present study, SOD1 protein from spinal cords of transgenic FALS mice was fractionated according to solubility in saline, zwitterionic, non-ionic or anionic detergents. Both endogenous mouse SOD1 and mutant human SOD1 were least soluble in SDS, followed by NP-40 and CHAPS, with an eight-fold greater detergent resistance of mutant protein overall. Importantly, high molecular weight mutant SOD1 complexes were isolated with SDS-extraction only. To reproduce SOD1 aggregate pathology in vitro, primary fibroblasts were isolated and cultured from neonatal transgenic FALS mice. Fibroblasts expressed abundant mutant SOD1 without spontaneous aggregation over time with passage. Proteasomal inhibition of cultures using lactacystin induced dose-dependent aggregation and increased the SDS-insoluble fraction of mutant SOD1, but not endogenous SOD1. In contrast, paraquat-mediated superoxide stress in fibroblasts promoted aggregation of endogenous SOD1, but not mutant SOD1. Treatment of cultures with peroxynitrite or the copper chelator diethyldithiocarbamate (DDC) alone did not modulate aggregation. However, DDC inhibited lactacystin-induced mutant SOD1 aggregation in transgenic fibroblasts, while exogenous copper slightly augmented aggregation. These data suggest that SOD1 aggregates may derive from proteasomal or oxidation-mediated oligomerisation pathways from mutant and endogenous subunits respectively. Furthermore, these pathways may be affected by copper availability. We propose that non-neural cultures such as these transgenic fibroblasts with inducible SOD1 aggregation may be useful for rapid screening of compounds with anti-aggregation potential in FALS.

  15. Decreased erythrocyte superoxide dismutase in elderly men with early nuclear cataract

    Directory of Open Access Journals (Sweden)

    Rose

    2014-04-01

    Full Text Available BACKGROUND Imbalance between oxidative processes and antioxidant defenses has been considered to play a role in cataractogenesis, particularly in diabetes patients. Superoxide dismutase (SOD is an important precursor for oxidative stress in the human lens, and its activity is mainly dependent on the copper and zinc levels in the body. The aim of this study was to compare erythrocyte SOD, erythrocyte zinc and total serum testosterone levels in male patients with early senile nuclear cataract and evaluate the correlations between the parameters in all subjects. METHODS A community-based study of cross-sectional design was conducted at Cilandak District Primary Health Center where 52 adult and 17 elderly men with early senile nuclear cataract were chosen as the study subjects. Erythrocyte SOD, erythrocyte zinc, serum testosterone, and fasting blood glucose (FBG levels were measured in all subjects. Nuclear cataract stage was assessed with the Pentacam® instrument (Oculus, Germany. Independent Student t test and Pearson’s correlation were used to analyze the results. RESULTS Erythrocyte SOD level was significantly decreased in elderly men compared to adult men (p=0.014. Erythrocyte zinc, serum testosterone and FBG did not differ significantly in adult and elderly males (at p=0.304; p=0.145;and p=0.376, respectively. Erythrocyte SOD activity was significantly associated with erythrocyte zinc level (r=0.486; p=0.048. CONCLUSIONS Lower erythrocyte SOD activity was found in elderly males than in adult males with early nuclear cataract. There was a relationship between erythrocyte SOD and erythrocyte zinc level in elderly males with early nuclear cataract.

  16. Overexpression of Extracellular Superoxide Dismutase Protects against Brain Injury Induced by Chronic Hypoxia

    Science.gov (United States)

    Zaghloul, Nahla; Patel, Hardik; Codipilly, Champa; Marambaud, Philippe; Dewey, Stephen; Frattini, Stephen; Huerta, Patricio T.; Nasim, Mansoor; Miller, Edmund J.; Ahmed, Mohamed

    2014-01-01

    Extracellular superoxide dismutase (EC-SOD) is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1%) for 10 days (H-KI) and compared to transgenic animals housed in room air (RA-KI), wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT). Overall brain metabolism evaluated by positron emission tomography (PET) showed that H-WT mice had significantly higher uptake of 18FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation. PMID:25268361

  17. Overexpression of extracellular superoxide dismutase protects against brain injury induced by chronic hypoxia.

    Directory of Open Access Journals (Sweden)

    Nahla Zaghloul

    Full Text Available Extracellular superoxide dismutase (EC-SOD is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1% for 10 days (H-KI and compared to transgenic animals housed in room air (RA-KI, wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT. Overall brain metabolism evaluated by positron emission tomography (PET showed that H-WT mice had significantly higher uptake of 18FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation.

  18. Model for biological communication in a nanofabricated cell-mimic driven by stochastic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Karig, David K [ORNL; Siuti, Piro [ORNL; Dar, Roy D. [University of Tennessee, Knoxville (UTK); Retterer, Scott T [ORNL; Doktycz, Mitchel John [ORNL; Simpson, Michael L [ORNL

    2011-01-01

    Cells offer natural examples of highly efficient networks of nanomachines. Accordingly, both intracellular and intercellular communication mechanisms in nature are looked to as a source of inspiration and instruction for engineered nanocommunication. Harnessing biological functionality in this manner requires an interdisciplinary approach that integrates systems biology, synthetic biology, and nanofabrication. Recent years have seen the amassing of a tremendous wealth of data from the sequencing of new organisms and from high throughput expression experiments. At the same time, a deeper fundamental understanding of individual cell function has been developed, as exemplified by the growth of fields such as noise biology, which seeks to characterize the role of noise in gene expression. The availability of well characterized biological components coupled with a deeper understanding of cell function has led to efforts to engineer both living cells and to create bio-like functionality in non-living substrates in the field of synthetic biology. Here, we present a model system that exemplifies the synergism between these realms of research. We propose a synthetic gene network for operation in a nanofabricated cell mimic array that propagates a biomolecular signal over long distances using the phenomenon of stochastic resonance. Our system consists of a bacterial quorum sensing signal molecule, a bistable genetic switch triggered by this signal, and an array of nanofabricated cell mimic wells that contain the genetic system. An optimal level of noise in the system helps to propagate a time-varying AHL signal over long distances through the array of mimics. This noise level is determined both by the system volume and by the parameters of the genetic network. Our proposed genetically driven stochastic resonance system serves as a testbed for exploring the potential harnessing of gene expression noise to aid in the transmission of a time-varying molecular signal.

  19. Language barriers between physicians and patients are not associated with thrombolysis of stroke mimics.

    Science.gov (United States)

    Rostanski, Sara K; Williams, Olajide; Stillman, Joshua I; Marshall, Randolph S; Willey, Joshua Z

    2016-10-01

    Acute stroke is a time-sensitive condition in which rapid diagnosis must be made in order for thrombolytic treatment to be administered. A certain proportion of patients who receive thrombolysis will be found on further evaluation to have a diagnosis other than stroke, so-called "stroke mimics." Little is known about the role of language discordance in the emergency department diagnosis of acute ischemic stroke. This is a retrospective analysis of all acute ischemic stroke patients who received IV tissue plasminogen activator (tPA) in our emergency department between July 2011 and December 2015. Baseline characteristics, patient language, and final diagnosis were compared between encounters in which the treating neurologist and patient spoke the same language (concordant cases) and encounters in which they did not (discordant cases). A total of 350 patients received IV tPA during the study period. English was the primary language for 52.6%, Spanish for 44.9%, and other languages for 2.6%; 60.3% of cases were classified as language concordant and 39.7% as discordant. We found no significant difference in the proportion of stroke mimics in the language concordant compared to discordant groups (16.6% vs 9.4%, p = 0.06). Similarly, the proportion of stroke mimics did not differ between English- and Spanish-speaking patients (15.8% vs 11.5%, p = 0.27). Language discordance was not associated with acute stroke misdiagnosis among patients treated with IV tPA. Prospective evaluation of communication during acute stroke encounters is needed to gain clarity on the role of language discordance in acute stroke misdiagnosis.

  20. Representing life in the Earth system with soil microbial functional traits in the MIMICS model

    Directory of Open Access Journals (Sweden)

    W. R. Wieder

    2015-02-01

    Full Text Available Projecting biogeochemical responses to global environmental change requires multi-scaled perspectives that consider organismal diversity, ecosystem processes and global fluxes. However, microbes, the drivers of soil organic matter decomposition and stabilization, remain notably absent from models used to project carbon cycle–climate feedbacks. We used a microbial trait-based soil carbon (C model, with two physiologically distinct microbial communities to improve current estimates of soil C storage and their likely response to perturbations. Drawing from the application of functional traits used to model other ecosystems, we incorporate copiotrophic and oligotrophic microbial functional groups in the MIcrobial-MIneral Carbon Stabilization (MIMICS model, which incorporates oligotrophic and copiotrophic functional groups, akin to "gleaner" vs. "opportunist" plankton in the ocean, or r vs. K strategists in plant and animals communities. Here we compare MIMICS to a conventional soil C model, DAYCENT, in cross-site comparisons of nitrogen (N enrichment effects on soil C dynamics. MIMICS more accurately simulates C responses to N enrichment; moreover, it raises important hypotheses involving the roles of substrate availability, community-level enzyme induction, and microbial physiological responses in explaining various soil biogeochemical responses to N enrichment. In global-scale analyses, we show that current projections from Earth system models likely overestimate the strength of the land C sink in response to increasing C inputs with elevated carbon dioxide (CO2. Our findings illustrate that tradeoffs between theory and utility can be overcome to develop soil biogeochemistry models that evaluate and advance our theoretical understanding of microbial dynamics and soil biogeochemical responses to environmental change.

  1. 111Cd TDPAC investigation of metal sites in superoxide dismutase: A comparison with X-ray diffraction data

    DEFF Research Database (Denmark)

    Bauer, R.; Bjerrum, M.J.; Danielsen, E.

    1990-01-01

    111Cd Time Differential Ferturbed γ-γ Angular Correlation (TDPAC) has been used to investigate the Zn-site in Cu2, Zn2-superoxide dismutase. These experiments show a clear difference between Cu(II)2 Cd2 SOD and Cu(I)2Cd2SOD. The result of Cu(II)2, Cd2-SOD agrees with the Angular Overlap Model (AOM...

  2. 111Cd TDPAC investigation of metal sites in superoxide dismutase: A comparison with X-ray diffraction data

    DEFF Research Database (Denmark)

    Bauer, R.; Bjerrum, M.J.; Danielsen, E.

    1990-01-01

    111Cd Time Differential Ferturbed γ-γ Angular Correlation (TDPAC) has been used to investigate the Zn-site in Cu2, Zn2-superoxide dismutase. These experiments show a clear difference between Cu(II)2 Cd2 SOD and Cu(I)2Cd2SOD. The result of Cu(II)2, Cd2-SOD agrees with the Angular Overlap Model (AOM...

  3. Peroxidase and superoxide dismutase activities in fig leaves in response to ambient air pollution in a subtropical city.

    Science.gov (United States)

    Li, M H

    2003-08-01

    Urban air pollution is a serious problem in both developing and developed countries, and antioxidant enzyme activities in plants have been suggested as a useful bioindicator of air pollution. In this study, the seasonal and spatial variability of peroxidase and superoxide dismutase activities were measured in leaves of Ficus microcarpa at eight sampling sites in the Taipei metropolitan area and one background site in rural area at each month for a year. The spatial pattern of peroxidase activity in figs collected from the Taipei metropolitan area was similar to the spatial pattern of O3 concentration in the Taipei metropolitan area. The peroxidase activities of Ficus microcarpa were significantly higher at sampling sites from the outer zone of the metropolitan area than those from the inner zone of the metropolitan area in spring and summer. On the other hand, the spatial pattern of superoxide dismutase activity in fig leaves did not show significant differences between the inner and outer zones of the Taipei metropolitan area. In addition, peroxidase activities, but not superoxide dismutase activities, of Ficus microcarpa were significantly higher in sites with high traffic density than those in low traffic density sites. Even though peroxidase activities in Ficus microcarpa tended to be higher in high traffic density sites or some sites with high ozone concentration, site-specific changes of peroxidase activity in Ficus microcarpa due to O3 pollution were not clearly observed in this study. Based on these results, neither peroxidase nor superoxide dismutase in Ficus microcarpa is a sensitive bioindicator for O3 pollution, although peroxidase shows some potential to be used as a general bioindicator of air quality.

  4. Effects of Hatha yoga exercise on plasma malondialdehyde concentration and superoxide dismutase activity in female patients with shoulder pain

    OpenAIRE

    Ha, Min-Sung; Kim, Do-Yeon; Baek, Yeong-Ho

    2015-01-01

    [Purpose] The purpose of this study was to analyze the effects of Hatha yoga exercise on plasma malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity in female patients with shoulder pain. [Subjects] Subjects comprised 20 female patients with shoulder pain. [Methods] Subjects were divided into 2 groups: a Hatha yoga exercise group (n = 10) and a control group that performed no exercise (n = 10). The subjects’ body composition, plasma malondialdehyde concentrations, and s...

  5. [The permeability of the hemato-encephalic barrier for superoxide dismutase following the unilateral intracarotid hyperperfusion of the cerebral vessels].

    Science.gov (United States)

    Aleksandrova, L A; Sorokoumova, V A; Shabunevich, L V; Pugacheva, E L

    1993-06-01

    On the model of acute blood-brain barrier injury in rats after a short-term hyperperfusion of one brain hemisphere with blood, the injection of exogenic superoxide dismutase (SOD) was accompanied by pronounced increase in the activity of SOD in the damaged brain tissue. This fact and other data of the authors on this model confirm the penetration of SOD over the microvessel endothelium into the extracellular space of the same damaged brain areas that are permeable for plasma albumin.

  6. Screening of drugs inhibiting in vitro oligomerization of Cu/Zn-superoxide dismutase with a mutation causing amyotrophic lateral sclerosis

    OpenAIRE

    Itsuki Anzai; Keisuke Toichi; Eiichi Tokuda; Atsushi Mukaiyama; Shuji Akiyama; Yoshiaki Furukawa

    2016-01-01

    Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) gene have been shown to cause a familial form of amyotrophic lateral sclerosis (SOD1-ALS). A major pathological hallmark of this disease is abnormal accumulation of mutant SOD1 oligomers in the affected spinal motor neurons. While no effective therapeutics for SOD1-ALS is currently available, SOD1 oligomerization will be a good target for developing cures of this disease. Recently, we have reproduced the formation of SOD1 oligomers ab...

  7. Zinc ascorbate has superoxide dismutase-like activity and in vitro antimicrobial activity against Staphylococcus aureus and Escherichia coli

    OpenAIRE

    2012-01-01

    Katsuhiro Iinuma, Isami TsuboiBML General Laboratory, Kawagoe, Saitama, JapanBackground: Acne vulgaris is a common dermatological disease, and its pathogenesis is multifactorial.Objective: We examined whether the ascorbic acid derivative zinc ascorbate has superoxide dismutase (SOD)-like activity. SOD is an enzyme that controls reactive oxygen species production. In addition, the in vitro antimicrobial activity of zinc ascorbate against the Gram-positive bacterium Staphylococcus aureus and th...

  8. Synthetic mimic of antimicrobial peptide with nonmembrane-disrupting antibacterial properties.

    Science.gov (United States)

    Gabriel, Gregory J; Madkour, Ahmad E; Dabkowski, Jeffrey M; Nelson, Christopher F; Nüsslein, Klaus; Tew, Gregory N

    2008-11-01

    Polyguanidinium oxanorbornene ( PGON) was synthesized from norbornene monomers via ring-opening metathesis polymerization. This polymer was observed to be strongly antibacterial against Gram-negative and Gram-positive bacteria as well as nonhemolytic against human red blood cells. Time-kill studies indicated that this polymer is lethal and not just bacteriostatic. In sharp contrast to previously reported SMAMPs (synthetic mimics of antimicrobial peptides), PGON did not disrupt membranes in vesicle-dye leakage assays and microscopy experiments. The unique biological properties of PGON, in same ways similar to cell-penetrating peptides, strongly encourage the examination of other novel guanidino containing macromolecules as powerful and selective antimicrobial agents.

  9. [Often an orthopedic problem can manifest as chest pain. Cervical vertebrae syndrome mimics myocardial infarct].

    Science.gov (United States)

    Fromm, B

    2002-04-25

    Up to 20% of all patients with pectoral symptoms have an underlying orthopedic problem. The most common orthopedic conditions that may mimic chest pain radiating into the left arm include slipped disc, cervicothoracic tension syndrome, blockage of intervertebral or rib joints, and intercostal neuralgia. Less common causes of such pain are arthrosis of the shoulder, spondylocystitis, osteoporotic fractures or tumors of the bone. Management is oriented to the underlying cause, and treatment extends from physiotherapeutic measures (rest, heat treatment) via medication (non-steroidal anti-inflammatory drugs, myotonolytic agents) to operative interventions.

  10. Cholesterol atheroembolism of the colon can mimic the endoscopic features of pseudomembranous colitis.

    Science.gov (United States)

    Lim, Geok-Hoon; Roslani, April Camilla; Pang, Brendan; Bih-Shiou, Charles Tsang

    2008-12-01

    The endoscopic features of cholesterol atheroembolism affecting the colon have not been extensively described in the literature, owing to the rarity of this entity. We report a middle-aged man who presented with hematochezia after recent coronary artery bypass graft surgery. Colonoscopy revealed ulcerative skip lesions with overlying slough resembling pseudomembranes distal to the transverse colon, inconsistent with the initial clinical impression of ischemic colitis. As a consequence of continued bleeding with hemodynamic instability, the patient underwent an extended low anterior resection with end transverse colostomy. Histology revealed cholesterol atheroembolism resulting in patchy ischemic ulceration of the colon. Colonic cholesterol atheroembolism can mimic the endoscopic features of pseudomembranous colitis.

  11. Chondromyxoid fibroma of the rib mimics a chondrosarcoma on 18F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William (Dept. of Nuclear Medicine, Brandon Regional Health Centre, Brandon (Canada)), email: makisw79@yahoo.com; Ciarallo, Anthony; Lisbona, Robert (Dept. of Nuclear Medicine, Royal Victoria Hospital, McGill Univ. Health Centre, Montreal (Canada))

    2011-06-15

    Chondromyxoid fibroma (CMF) is a rare benign bone tumor of chondroid origin that occurs mostly in the metaphyses of long bones. CMF can occasionally mimic a chondrosarcoma on CT, and the literature on the 18F-FDG PET/CT imaging characteristics of CMF tumors is limited. In the presented case, a large histologically proven CMF chest wall mass was initially misinterpreted as a chondrosarcoma. This case highlights a potential pitfall in the PET/CT evaluation of these rare benign bone tumors

  12. Tsukamurella: an unrecognized mimic of atypical mycobacterial keratitis? The first case report.

    Science.gov (United States)

    Tam, Patrick M K; Young, Alvin L; Cheng, Lulu; Congdon, Nathan; Lam, Philip T H

    2010-03-01

    The purpose of this study was to report on Tsukamurella as a mimic of atypical mycobacterial infection. We report a patient who had received repeated corneal grafts with culture-proven Tsukamurella keratitis. A slow-progressing corneal abscess that initially developed adjacent to a corneal stitch responded poorly to empiric antibiotic treatment. A preliminary culture report revealed fast-growing mycobacterial species. Treatment adjustments successfully controlled the disease. A final diagnosis of Tsukamurella was subsequently made on the basis of cultures. Tsukamurella exhibits laboratory similarities to mycobacteria and should be considered in the differential of atypical infection of the ocular surface.

  13. Race-related cognitive test bias in the active study: a mimic model approach.

    Science.gov (United States)

    Aiken Morgan, Adrienne T; Marsiske, Michael; Dzierzewski, Joseph M; Jones, Richard N; Whitfield, Keith E; Johnson, Kathy E; Cresci, Mary K

    2010-10-01

    The present study investigated evidence for race-related test bias in cognitive measures used in the baseline assessment of the ACTIVE clinical trial. Test bias against African Americans has been documented in both cognitive aging and early life span studies. Despite significant mean performance differences, Multiple Indicators Multiple Causes (MIMIC) models suggested most differences were at the construct level. There was little evidence that specific measures put either group at particular advantage or disadvantage and little evidence of cognitive test bias in this sample. Small group differences in education, cognitive status, and health suggest positive selection may have attenuated possible biases.

  14. Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Vucic V.

    2006-01-01

    Full Text Available Gamma-irradiation (gamma-IR is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD, specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001 antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control to 49% (IR cells, with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

  15. Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    V. Vucic

    2006-02-01

    Full Text Available Gamma-irradiation (gamma-IR is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD, specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001 antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control to 49% (IR cells, with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

  16. Active Fe-Containing Superoxide Dismutase and Abundant sodF mRNA in Nostoc commune (Cyanobacteria) after Years of Desiccation

    Science.gov (United States)

    Shirkey, Breanne; Kovarcik, Don Paul; Wright, Deborah J.; Wilmoth, Gabriel; Prickett, Todd F.; Helm, Richard F.; Gregory, Eugene M.; Potts, Malcolm

    2000-01-01

    Active Fe-superoxide dismutase (SodF) was the third most abundant soluble protein in cells of Nostoc commune CHEN/1986 after prolonged (13 years) storage in the desiccated state. Upon rehydration, Fe-containing superoxide disumutase (Fe-SOD) was released and the activity was distributed between rehydrating cells and the extracellular fluid. The 21-kDa Fe-SOD polypeptide was purified, the N terminus was sequenced, and the data were used to isolate sodF from the clonal isolate N. commune DRH1. sodF encodes an open reading frame of 200 codons and is expressed as a monocistronic transcript (of approximately 750 bases) from a region of the genome which includes genes involved in nucleic acid synthesis and repair, including dipyrimidine photolyase (phr) and cytidylate monophosphate kinase (panC). sodF mRNA was abundant and stable in cells after long-term desiccation. Upon rehydration of desiccated cells, there was a turnover of sodF mRNA within 15 min and then a rise in the mRNA pool to control levels (quantity of sodF mRNA in cells in late logarithmic phase of growth) over approximately 24 h. The extensive extracellular polysaccharide (glycan) of N. commune DRH1 generated superoxide radicals upon exposure to UV-A or -B irradiation, and these were scavenged by SOD. Despite demonstrated roles for the glycan in the desiccation tolerance of N. commune, it may in fact be a significant source of damaging free radicals in vivo. It is proposed that the high levels of SodF in N. commune, and release of the enzyme from dried cells upon rehydration, counter the effects of oxidative stress imposed by multiple cycles of desiccation and rehydration during UV-A or -B irradiation in situ. PMID:10613879

  17. In Vitro Study of Influence of Mimic Cardiac Rate on Hydrodynamics of the Different Mechanical Cardiac Valve Prostheses

    Institute of Scientific and Technical Information of China (English)

    CHU Yin-ping; CHENG Jin-lian; CHEN Ru-kun; FAN Yu-bo; PU Fang

    2005-01-01

    Objective:To assess the influence of mimic cardiac rate on hydrodynamics of the different mechanical prosthetic cardiac valves. Methods: US-made CarboMedics bileaflet valve and China-made Jiuling bileaflet valve and C-L tilting disc valve have been tested in a pulsatile flow simulator in the aortic position. The testing condition was set at the mimic cardiac rate of 55 beats/min,75 beats/min,100beats/min and a constant mimic cardiac output of 4L/min. The mean pressure differences (△P) ,leakage volumes (LEV) and closing volumes (CLV) across each valve,and the effective orifice areas(EOA) have been analyzed. Results:Within the range of physiology,the △P,LEV and CLV were falling as the increasing of mimic cardiac rate,and the extent of variance was larger. The EOA was increasing with the increase of the mimic cardiac rate. It is a different response as the altering of the cardiac rate for the different type of the mechanical prosthetic cardiac valves.Conclusions:The change of the mimic cardiac rate can affect the hydrodynamics of the mechanical prosthetic cardiac valves. The hydrodynamics of the bileaflet valve prosthesis is better than the tilting disc valve.

  18. Expedient synthesis of triazole-linked glycosyl amino acids and peptides.

    NARCIS (Netherlands)

    Kuijpers, B.H.M.; Groothuys, S.; Keereweer, A.R.; Quaedflieg, P.J.; Blaauw, R.H.; Delft, F.L. van; Rutjes, F.P.J.T.

    2004-01-01

    [structure: see text] An expedient, high-yielding synthesis of two types of triazole-linked glycopeptides is described. These novel and stable glycopeptide mimics were prepared via Cu(I)-catalyzed [3 + 2] cycloaddition of either azide-functionalized glycosides and acetylenic amino acids or acetyleni

  19. Identification and Characterization of Peptide Mimics of Blood Group A Antigen

    Institute of Scientific and Technical Information of China (English)

    Zhaoming TANG; Lin WANG; Lihua HU; Yirong LI; Tianpen CUI; Juan XIONG; Lifang DOU

    2008-01-01

    In order to investigate peptide mimics of carbohydrate blood group A antigen, a phage display 12-met peptide library was screened with a monoclonal antibody against blood group A antigen, NaM87-1F6. The antibody-binding properties of the selected phage peptides were evaluated by phage ELISA and phage capture assay. The peptides were co-expressed as glutathione S-transferase (GST) fusion proteins. RBC agglutination inhibition assay was performed to assess the natural blood group A antigen-mimicking ability of the fusion proteins. The results showed that seven phage clones selected bound to NaM87-1F6 specifically, among which, 6 clones bore the same peptide sequence, EYWYCGMNRTGC and another harbored a different one QIWYERTLPFrF. The two peptides were successfully expressed at the N terminal of GST protein. Both of the fusion proteins inhibited the RBC agglutination mediated by anti-A serum in a concentration-dependent manner. These results suggested that the fusion proteins based on the selected peptides could mimic the blood group A an- tigen and might be used as anti-A antibody-adsorbing materials when immunoabsorption was applied in ABO incompatible transplantation.

  20. Comprehending body language and mimics: an ERP and neuroimaging study on Italian actors and viewers.

    Directory of Open Access Journals (Sweden)

    Alice Mado Proverbio

    Full Text Available In this study, the neural mechanism subserving the ability to understand people's emotional and mental states by observing their body language (facial expression, body posture and mimics was investigated in healthy volunteers. ERPs were recorded in 30 Italian University students while they evaluated 280 pictures of highly ecological displays of emotional body language that were acted out by 8 male and female Italian actors. Pictures were briefly flashed and preceded by short verbal descriptions (e.g., "What a bore!" that were incongruent half of the time (e.g., a picture of a very attentive and concentrated person shown after the previous example verbal description. ERP data and source reconstruction indicated that the first recognition of incongruent body language occurred 300 ms post-stimulus. swLORETA performed on the N400 identified the strongest generators of this effect in the right rectal gyrus (BA11 of the ventromedial orbitofrontal cortex, the bilateral uncus (limbic system and the cingulate cortex, the cortical areas devoted to face and body processing (STS, FFA EBA and the premotor cortex (BA6, which is involved in action understanding. These results indicate that face and body mimics undergo a prioritized processing that is mostly represented in the affective brain and is rapidly compared with verbal information. This process is likely able to regulate social interactions by providing on-line information about the sincerity and trustfulness of others.