BibSonomy publications for /tag/ifzThu Nov 27 09:35:31 CET 2008WATER AIR AND SOIL POLLUTION1-4221-237Statistical modeling of the partitioning of nonylphenol in soil1722006IFZ artificial_neural_networks multiple_linear_regression_analysis nonylphenol pedotransfer_function validation Partition coefficients K-P of nonylphenol (NP) in soil were determined for 193 soil samples which differed widely in content of soil organic carbon (SOC), hydrogen activity, clay content, and in the content of dissolved organic carbon (DOC). By means of multiple linear regression analysis (MLR), pedotransfer functions were derived to predict partition coefficients from soil data. SOC and pH affected the sorption, though the latter was in a range significantly below the pK(a) of NP. Quality of soil organic matter presumably plays an important but yet not quantified role in sorption of NP. For soil samples with SOC values less than 3 g kg(-1), model prediction became uncertain with this linear approach. We suggest that using only SOC and pH data results in good prediction of NP sorption in soils with SOC higher than 3 g kg(-1). Considering the varying validity of the linear model for different ranges of the most sensitive parameter SOC, a more flexible, nonlinear approach was tested. TheTue Nov 18 12:42:48 CET 2008Journal of Animal Physiology and Animal NutritionAugustPMID: 18662358481-91Estimation of the selenium requirement of growing guinea pigs (Cavia porcellus)922008Animal_Feed Animal_Nutrition_Physiology Animals Dose-Response_Relationship Drug Glutathione_Peroxidase Guinea_Pigs IFZ Male Nutritional_Requirements Nutritional_Status Organ_Specificity Random_Allocation Selenium Weight_Gain The aim of the study was to determine the selenium (Se) requirement of guinea pigs as a species unable to synthesize ascorbic acid. Forty-nine male guinea pigs (average weight 208 +/- 3.5 g) were divided into an initial status group and six experimental groups. The animals received a Se deficient Torula yeast based basal diet ({\textless}0.02 mg Se and 26 mg alpha-tocopherol/kg) or a Se addition of 0.05, 0.10, 0.15, 0.20 and 0.25 mg/kg diet as sodium selenate for 10 weeks. There was no significant difference in weight gain (final weight 643 +/- 21 g) between the groups and no clinical symptoms of Se deficiency occurred. With the exception of the testes, there was an increasing Se concentration in liver, plasma and haemolysate dependent on supplementation level. Glutathione peroxidase was determined in the plasma and Se dependent glutathione peroxidase (GPx1) in haemolysate, liver, kidney, heart and lung. Thioredoxin reductase (TR) activity was measured in liver, kidney and heart and deiodinase activity in the liver. A phospholipid hydroperoxide reducing activity with Se influence was determined in liver, kidney, heart, testes and brain. With the exception of GPx1 activity in heart and haemolysate and TR activity in the kidney, all enzymes already reached their maximal activity at 0.05 mg Se/kg diet. The activities of GPx1 and TR were used as parameters for broken line analysis and a Se requirement of 0.080 mg Se/kg diet was derived as sufficient for growing guinea pigs adequately supplied with vitamin E.Tue Nov 18 12:38:00 CET 2008British Poultry ScienceSeptemberPMID: 18836905583-91Selenium requirement of growing male turkeys492008IFZ imported 1. The aim of the experiment was to estimate the selenium requirement of growing male turkeys using the selenium concentrations in different organs and blood plasma and by fitting a continuous broken line to the activity of glutathione peroxidase in liver and plasma. 2. Newly hatched male BUT BIG 6 turkeys were fed either on the selenium deficient basal soybean-maize diets (selenium {\textless}0.010 mg/kg diet) adapted to the NRC (1994) and GfE (2004) recommendations for growing turkeys from 0 to 2 weeks (prestarter diet) and 3 to 5 weeks (starter diet) or the basal diets supplemented with 0.10, 0.15, 0.20, 0.25, 0.30, 0.35 or 0.40 mg selenium/kg diet as sodium selenate. Vitamin E was supplemented adequately in all diets. 3. After 5 weeks the weight in all groups (mean 2568 g) exceeded the expectations for the genotype investigated. Feed consumption and weight gain were however significantly reduced in the group receiving the selenium-deficient diet. 4. After 2 and 5 weeks selenium concentration and activity of glutathione peroxidase in the plasma and the organs examined were greatly influenced by selenium supplementation. 5. Under the conditions investigated, 0.30 mg Se/kg diet was necessary for fast-growing male turkeys to ensure maximum selenium accumulation in the organs examined and maximum glutathione peroxidase activity in plasma and liver.Tue Nov 18 12:38:00 CET 2008The Journal of Nutritional BiochemistryJulyPMID: 18602818Regulation of the insulin antagonistic protein tyrosine phosphatase 1B by dietary Se studied in growing rats2008IFZ imported Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme in the counterregulation of insulin signaling, and its physiological modulation depends on H(2)O(2) and glutathione (GSH). Se via GSH peroxidases (GPxs) and its specific metabolism is involved in the removal of H(2)O(2) and in the regulation of GSH metabolism. Recent results from animal trials and epidemiological studies with humans have shown that a high GPx1 activity or a permanent surplus of Se may promote the development of obesity and diabetes. Our nutrition physiological study with 7x7 growing rats was carried out to examine if PTP1B is modulated by Se supplements and, thus, may represent one trigger mediating these undesirable metabolic effects of Se. One group of rats was fed an Se-deficient diet for 8 weeks. The diets of the other six groups contained Se as selenite or selenate according to the recommendations (0.20 mg/kg diet) and at two supranutritional levels (1.00 and 2.00 mg/kg diet). All Se-supplemented animals featured a significantly higher body weight (6-14\%) compared to their Se-deficient companions. Expression and activity of GPx1 in the liver of Se supplemented animals was 10- and 70-fold higher compared to Se deficiency. The detailed study of PTP1B regulation using an enzymatic assay and Western Blot analysis with an antibody against protein glutathionylation revealed that PTP1B was significantly up-regulated by both a maximization of GPx1 activity and by increasing dietary Se supply, reducing its inhibition via glutathionylation. Selenate effected a stronger PTP activation compared to selenite. In conclusion, our results suggest that the modulation of PTP1B activity may represent one plausible mechanism by which a long-term intake of Se supplements exceeding the requirements can promote the development of obesity and diabetes and needs further intensive investigation.Thu Nov 06 14:34:38 CET 2008FUNCTIONAL PLANT BIOLOGY7633-639Silicon-mediated improvement in the salt resistance of wheat (Triticum aestivum) results from increased sodium exclusion and resistance to oxidative stress352008IFZ ascorbate cell_wall glutathione salinity Silicon (Si) is reported to reduce the effect of salinity on wheat (Triticum aestivum L.) and other crops. In the present study, Si decreased plant Na+ uptake and shoot : root Na+ distribution of a salt-resistant as well as a salt-sensitive wheat genotype. Reduced shoot Na+ concentration and increased shoot K+ : Na+ ratio led to improved plant growth. Silicon increased cell-wall Na+ binding from 49% in SARC-1 and 37% in 7-Cerros under salinity to 87% in SARC-1 and 79% in 7-Cerros under salinity + silicon. It may also have resulted in decreased potentially toxic leaf sap Na+ concentration. The concentration of glutathione, an important antioxidant in plants, was increased due to the addition of Si under saline conditions. The salt-resistant wheat genotype SARC-1 was less Si-responsive in terms of shoot fresh weight, having a 39% increase compared with a 49% increase in 7-Cerros, as well as root fresh weight, having a 12% increase compared with a 22% in 7-Cerros. Tue Oct 14 16:07:18 CEST 2008Spiegel der Forschung142-47Molekulare Maschinen und Alterung � der humane Redoxstoffwechsel242007IFZ imported Tue Oct 14 16:07:18 CEST 2008Biospektrum07138-141Antioxidative Enzyme des Malariaerregers als Targets von Bonaria-Medikamenten022007IFZ imported Tue Oct 14 16:07:18 CEST 2008PLoS ONE6e2474-e2474Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite32008Animals Base_Sequence Blotting DNA_Primers IFZ Life_Cycle_Stages Messenger Peroxidases Plasmodium_berghei RNA Rats Reverse_Transcriptase_Polymerase_Chain_Reaction Western Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the rodent model malaria parasite and phenotypic analysis during life cycle progression revealed a non-vital role in vivo. Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies.Tue Oct 14 16:07:18 CEST 2008J Med Chem51260-1277Antimalarial dual drugs based on potent inhibitors of glutathione reductase from Plasmodium falciparum512008/03/13/Animals Antimalarials Biological_Transport Cell_Line Combination Drug_Resistance Drug_Therapy Glutathione_Reductase Humans IFZ Inbred_BALB_C Malaria Mice Naphthalenes Parasitic_Sensitivity_Tests Plasmodium_berghei Plasmodium_falciparum Structure-Activity_Relationship Tumor chloroquine Plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. As a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. Their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant strains of Plasmodium, alone or in drug combination, and in the Plasmodium berghei rodent model. In particular, two tertiary amides 34 and 36 showed potent antimalarial activity in the low nanomolar range against CQ-resistant parasites. The ability to compete both for (Fe (III))protoporphyrin and for chloroquine transporter was determined. The data are consistent with the presence of a carrier for uptake of the short chloroquine analogue 2 but not for the potent antimalarial amide 34, suggestinTue Oct 14 16:07:18 CEST 2008Antimicrob Agents Chemother1183-191Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum522008/01//Aerobiosis Animals Binding_Sites Disulfides Humans Hydrogen-Ion_Concentration IFZ Kinetics Methylene_Blue Oxidation-Reduction Oxidoreductases Plasmodium_falciparum Protozoan_Proteins Substrate_Specificity Methylene blue (MB) has experienced a renaissance mainly as a component of drug combinations against Plasmodium falciparum malaria. Here, we report biochemically relevant pharmacological data on MB such as rate constants for the uncatalyzed reaction of MB at pH 7.4 with cellular reductants like NAD(P)H (k = 4 M(-1) s(-1)), thioredoxins (k = 8.5 to 26 M(-1) s(-1)), dihydrolipoamide (k = 53 M(-1) s(-1)), and slowly reacting glutathione. As the disulfide reductases are prominent targets of MB, optical tests for enzymes reducing MB at the expense of NAD(P)H under aerobic conditions were developed. The product leucomethylene blue (leucoMB) is auto-oxidized back to MB at pH 7 but can be stabilized by enzymes at pH 5.0, which makes this colorless compound an interesting drug candidate. MB was found to be an inhibitor and/or a redox-cycling substrate of mammalian and P. falciparum disulfide reductases, with the kcat values ranging from 0.03 s(-1) to 10 s(-1) at 25 degrees C. Kinetic spectroscoTue Oct 14 16:07:18 CEST 2008PROTEOMICS5711-721SELDI-TOF-MS analysis of chloroquine resistant and sensitive Plasmodium falciparum strains72007IFZ Plasmodium_falciparum SELDI chloroquine mechanism_of_drug_action The resistance of the malarial parasite Plasmodium falciparum to chloroquine represents an emerging problem since neither mode of drug action nor mechanisms of resistance are fully elucidated. We describe a protein expression profiling approach by SELDI-TOF-MS as a useful tool for studying the proteome of malarial parasites. Reproducible and complex protein profiles of the P. falciparum strains K1, Dd2, HB3 and 3D7 were measured on four array types. Hierarchical clustering led to a clear separation of the two major subgroups ��resistant" and ��sensitive" as well as of the four parasite strains. Our study delivers sets of regulated proteins derived from extensive comparative analyses of 64 P.falciparum protein profiles. A group of 12 peaks reflecting proteome changes under chloroquine treatment and a set of 10 potential chloroquine resistance markers were defined. Three of these regulated peaks were preparatively enriched, purified and identified. They were shown to represent the plasmoTue Oct 14 16:07:18 CEST 2008e.velop" 52 (Internetmagazin der Bundesregierung zur Entwicklungspolitik)Warum haben Kinder in Afrika so oft Fieber?522007IFZ imported Tue Oct 14 16:07:18 CEST 2008SEMINARS IN CANCER BIOLOGY6452-465On the potential of thioredoxin reductase inhibitors for cancer therapy162006IFZ cancer chemotherapy inhibitor redox_sensitivity reductase thioredoxin Thioredoxin reductase (TrxR)-as part of a major thiol regulating system-allows redox metabolism to adjust to cellular requirements. Therefore, changes at the redox level reflect as a pars pro toto changes concerning the entire cell. Three different TrxR isoenzymes, TrxR1 as cytosolic, TrxR2 as mitochondrial, and TrxR3 as testis-specific thiol regulator are known. All three enzymes contain a reactive and solvent accessible selenocysteine residue which is located on a flexible C-terminal arm of the protein. This selenocysteine is essentially involved in the catalytic cycle of TrxR and thus represents an attractive binding site for inhibitors. Many tumor cells have elevated TrxR levels and TrxR has been shown to play a major role in drug resistance. Inhibition of TrxR and its related redox reactions may thus contribute to a successful single, combinatory or adjuvant cancer therapy. A great number of effective natural and synthetic TrxR inhibitors are now available possessing antitumor potTue Oct 14 16:07:18 CEST 2008INTERNATIONAL JOURNAL FOR PARASITOLOGYSuppl. 1S37Functional characterization of Plasmodium redoxrelated enzymes382008IFZ imported Tue Oct 14 16:07:18 CEST 2008Frontiers in Drug Design and Discovery225-255Structure-based drug development against malaria32007IFZ imported Tue Oct 14 16:07:18 CEST 2008INTERNATIONAL JOURNAL FOR PARASITOLOGYSuppl. 1S28Quantitative proteomics of Plasmodium falciparum protein expression following drug exposure382008IFZ imported Tue Oct 14 16:07:18 CEST 2008Org Biomol Chem152731-2742The aza-analogues of 1,4-naphthoquinones are potent substrates and inhibitors of plasmodial thioredoxin and glutathione reductases and of human erythrocyte glutathione reductase62008/08/07/IFZ imported Various aza-analogues of 1,4-naphthoquinone and menadione were prepared and tested as inhibitors and substrates of the plasmodial thioredoxin and glutathione reductases as well as the human glutathione reductase. The replacement of one to two carbons at the phenyl ring of the 1,4-naphthoquinone core by one to two nitrogen atoms led to an increased oxidant character of the molecules in accordance with both the redox potential values and the substrate efficiencies. Compared to the 1,4-naphthoquinone and menadione, the quinoline-5,8-dione 1 and both quinoxaline-5,8-diones 5 and 6 behaved as the most efficient subversive substrates of the three NADPH-dependent disulfide reductases tested. Modulation of these parameters was observed by alkylation of the aza-naphthoquinone core.Tue Oct 14 16:07:18 CEST 2008Biol Chem101069-1081Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents3882007/10//2'-disulfonic_Acid 4-Acetamido-4'-isothiocyanatostilbene-2 Allyl_Compounds Anticarcinogenic_Agents Cell_Cycle Cell_Line Cell_Proliferation Disulfides Dose-Response_Relationship Drug Glutathione Glutathione_Transferase Humans IFZ Oxidation-Reduction Sulfur_Compounds Thioredoxin-Disulfide_Reductase Thioredoxins Tumor Up-Regulation glutathione_peroxidase isothiocyanates We studied the effects of sulfur-containing chemopreventive agents, including allyl sulfides and isothiocyanates, on human redox networks. Isothiocyanates inhibited isolated redox-active enzymes in a time- and dose-dependent manner. As shown for the most active compound, benzyl isothiocyanate (BITC), on thioredoxin reductase, the inhibition has an initial competitive part (Ki=6.1+/-1.0 microM) followed by a time-dependent irreversible inhibition (k2=72.8+/-25.5 M(-1) s(-1)). Also, glutathione reductase and glutathione S-transferase were irreversibly modified by BITC. Sulforaphane led to irreversible inhibition of the studied redox enzymes, but with 5-10 times lower k2 values. In contrast, allyl sulfides had only moderate effects on the tested enzymes. However, diallyl disulfide was found to react directly with reduced glutathione (k2=100 M(-2) s(-1)). This reaction might contribute to enhanced oxidative stress and the induction of the selenoprotein glutathione peroxidase as determined Tue Oct 14 16:07:18 CEST 2008Biol Chem2207-219Resveratrol modulates mRNA transcripts of genes related to redox metabolism and cell proliferation in non-small-cell lung carcinoma cells3882007/02//Apoptosis Carcinoma Cell_Count Cell_Cycle Cell_Proliferation Cultured Dose-Response_Relationship Drug Genetic Glutathione Humans IFZ Lung_Neoplasms Messenger Non-Small-Cell_Lung Oxidation-Reduction Phosphotransferases RNA Reverse_Transcriptase_Polymerase_Chain_Reaction Sensitivity_and_Specificity Stilbenes Structure-Activity_Relationship Transcription Tumor_Cells glutathione_peroxidase Resveratrol is a polyphenolic chemopreventive agent that has been shown to influence cellular redox reactions. As a systematic approach to elucidating the complex effects of resveratrol on eukaryotic cells, we studied its dose-dependent effects on the transcript levels of genes and activities of enzymes related to redox metabolism, cell cycle regulation, and apoptotic cascades in the cancer cell line A549. Glutathione peroxidase (GPx)1 mRNA levels, as well as GPx and thioredoxin reductase (TrxR) activities, were significantly increased after resveratrol treatment, whereas total glutathione concentrations decreased. Increased transcript levels were also detected for selenophosphate synthetase 2 and superoxide dismutase 2. However, mRNA levels of thioredoxin, TrxR, glutathione reductase, glutathione S-transferase, superoxide dismutase 1, and catalase were not altered. Among the 12 genes studied that are related to the cell cycle, differentiation and apoptosis, mRNA levels of six genes, iTue Oct 14 16:07:18 CEST 2008Blood83560-3566Molecular basis of glutathione reductase deficiency in human blood cells1092007/04/15/Alleles Amino_Acid_Substitution Cataract Child Codon Erythrocytes Favism Female Genetic_Diseases Glutathione_Reductase Heterozygote Humans IFZ Inborn Infant Jaundice Leukocytes Male Middle_Aged Neonatal Newborn Nonsense Preschool Protein_Structure Quaternary Sequence_Deletion Tertiary Hereditary glutathione reductase (GR) deficiency was found in only 2 cases when testing more than 15 000 blood samples. We have investigated the blood cells of 2 patients (1a and 1b) in a previously described family suffering from favism and cataract and of a novel patient (2) presenting with severe neonatal jaundice. Red blood cells and leukocytes of the patients in family 1 did not contain any GR activity, and the GR protein was undetectable by Western blotting. Owing to a 2246-bp deletion in the patients' DNA, translated GR is expected to lack almost the complete dimerization domain, which results in unstable and inactive enzyme. The red blood cells from patient 2 did not exhibit GR activity either, but the patient's leukocytes contained some residual activity that correlated with a weak protein expression. Patient 2 was found to be a compound heterozygote, with a premature stop codon on one allele and a substitution of glycine 330, a highly conserved residue in the superfamily of NifzCommunity for tag(s) ifz