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Geoffrey A Codd - One of the best experts on this subject based on the ideXlab platform.
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Laboratory studies of dissolved radiolabelled Microcystin-LR in lake water.
Water Research, 2003Co-Authors: Per Hyenstrand, James S Metcalf, Kenneth A Beattie, Geoffrey A Codd, Thomas Rohrlack, Kirsten ChristoffersenAbstract:Abstract The fate of dissolved Microcystin-LR was studied in laboratory experiments using surface water taken from a eutrophic lake. Based on initial range finding, a concentration of 50 μg l −1 dissolved 14 C-Microcystin-LR was selected for subsequent time-course experiments. The first was performed in May before the cyanobacterial bloom season and low increases in the radioactivity of particulate fractions occurred with an approx. halving of the cyano-toxin during 4 days. The radioactivity of the dissolved fraction remained stable and there was no significant formation of radiolabelled inorganic carbon. A second time-course experiment was performed in September during the cyanobacterial bloom season. At the end of the four-day incubation period, the Microcystin-LR concentration had decreased to an undetectable level and 24% of the added radiolabelled substance was found in different particulate fractions. The study demonstrated that biodegradation of dissolved Microcystin-LR occurred in water collected at a lake surface with carbon dioxide as a major end-product.
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effects of adsorption to plastics and solvent conditions in the analysis of the cyanobacterial toxin Microcystin LR by high performance liquid chromatography
Water Research, 2001Co-Authors: Per Hyenstrand, James S Metcalf, Kenneth A Beattie, Geoffrey A CoddAbstract:Effects of adsorption to plastics and solvent conditions in the high performance liquid chromatographic analysis of the cyanobacterial toxin Microcystin-LR were investigated. Aqueous Microcystin-LR readily adsorbed to the disposable polypropylene pipette tips commonly used in laboratory manipulations. This was not affected by the pH or salinity of the solution. Furthermore, dilutions of Microcystin-LR in varying concentrations of methanol and acetonitrile influenced the quantification of the Microcystin-LR concentration by high performance liquid chromatography.
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immuno crossreactivity and toxicity assessment of conjugation products of the cyanobacterial toxin Microcystin LR
Fems Microbiology Letters, 2000Co-Authors: James S Metcalf, Kenneth A Beattie, Stephan Pflugmacher, Geoffrey A CoddAbstract:Immunoassays are increasingly used to investigate the production, properties and fates of the cyanobacterial hepatotoxic Microcystins in vitro and in vivo. Responses of an ELISA immunoassay to Microcystins have been determined using the authentic toxin antigen, Microcystin-LR, and conjugation products between the toxin and glutathione, cysteine-glycine and cysteine. The antibodies against Microcystin-LR crossreacted with the toxin conjugation products with similar affinities (96–112%) to that of Microcystin-LR, when assayed at a concentration of 1 μg l−1. Toxicity assessment of the conjugates, in comparison to Microcystin-LR, indicated a reduction according to mouse bioassay. In vitro protein phosphatase inhibition assay indicated that the conjugates possessed approximately 3–9-fold lower toxicity than Microcystin-LR.
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cyanobacterial Microcystin LR is a potent and specific inhibitor of protein phosphatases 1 and 2a from both mammals and higher plants
FEBS Letters, 1990Co-Authors: Carol Mackintosh, Kenneth A Beattie, Susanne Klumpp, Philip Cohen, Geoffrey A CoddAbstract:Abstract The cyclic heptapeptide, Microcystin-LR, inhibits protein phosphatases 1 (PP1) and 2A (PP2A) with K i , values below 0.1 nM. Protein phosphatase 2B is inhibited 1000-fold less potently, while six other phosphatases and eight protein kinases tested are unaffected. These results are strikingly similar to those obtained with the tumour promoter okadaic acid. We establish that okadaic acid prevents the binding of Microcystin-LR to PP2A, and that protein inhibitors 1 and 2 prevent the binding of Microcystin-LR to PP1. We discuss the possibility that inhibition of PP1 and PP2A accounts for the extreme toxicity of Microcystin-LR, and indicate its potential value in the detection and analysis of protein kinases and phosphatases.
Hirota Fujiki - One of the best experts on this subject based on the ideXlab platform.
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Tumor Promoters - Microcystin-LR, Nodularin and TNF-α and Human Cancer Development
Anti-cancer Agents in Medicinal Chemistry, 2011Co-Authors: Hirota Fujiki, Masami SuganumaAbstract:: Microcystin-LR and nodularin, along with okadaic acid, are potent inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A). The mechanisms of action of Microcystin-LR and nodularin in the liver and that of okadaic acid, a potent tumor promoter on mouse skin, have attracted the attention of the scientists. This paper reviews several topics: new inhibitors of PP1 and PP2A with new chemical structures, structure-function relationships for both receptor binding and inhibition of protein phosphatases, the crystal structure of PP1 or PP2A-toxin complex, induction of gene expression and apoptosis. These subjects were studied by using in vitro and in vivo experimental systems. Two-stage carcinogenesis experiments with Microcystin-LR and nodularin for the first time demonstrated that Microcystin-LR is a new tumor promoter in rat liver initiated with diethylnitrosamine (DEN), and that nodularin is a potent tumor promoter associated with weak initiating activity in rat liver initiated with DEN. A working group of WHO (IARC) concluded that Microcystin-LR is "possibly carcinogenic to humans" and that nodularin is "not classifiable as to carcinogenicity". Our studies revealed that chemical tumor promoters are inducers of TNF-α in the cells of target tissues and that TNF-α is an endogenous tumor promoter. This advance in carcinogenesis made it possible to look for the link between chemical tumor promoters and endogenous tumor promoters, such as TNF-α and IL-1. The carcinogenic features of TNF-α are described in this review, and the TNF-α inducing protein (Tipα) of Helicobacter pylori genome is presented as an example of a tumor promoter of human stomach cancer development.
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Liver tumor promotion by the cyanobacterial cyclic peptide toxin Microcystin-LR
Journal of Cancer Research and Clinical Oncology, 1992Co-Authors: Rie Nishiwaki-matsushima, Tetsuya Ohta, Shinji Nishiwaki, Masami Suganuma, Kiyomi Kohyama, Takatoshi Ishikawa, Wayne W. Carmichael, Hirota FujikiAbstract:Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed Microcystins, which cause liver damage in wild and domesticated animals. The most widely studied Microcystin is Microcystin-LR, a heptapeptide containing the two l -amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by Microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that Microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathione S -transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that Microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver.
Gary J Jones - One of the best experts on this subject based on the ideXlab platform.
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biodegradation of the cyanobacterial toxin Microcystin LR in natural water and biologically active slow sand filters
Water Research, 2006Co-Authors: David G Bourne, Gary J Jones, Robert L Blakeley, Peter W RiddlesAbstract:A bacterium (MJ-PV) previously demonstrated to degrade the cyanobacterial toxin Microcystin LR, was investigated for bioremediation applications in natural water microcosms and biologically active slow sand filters. Enhanced degradation of Microcystin LR was observed with inoculated (1 x 10(6) cell/mL) treatments of river water dosed with Microcystin LR (> 80% degradation within 2 days) compared to uninoculated controls. Inoculation of MJ-PV at lower concentrations (1 x 10(2)-1 x 10(5)cells/mL) also demonstrated enhanced Microcystin LR degradation over control treatments. Polymerase chain reactions (PCR) specifically targeting amplification of 16S rDNA of MJ-PV and the gene responsible for initial degradation of Microcystin LR (mLRA) were successfully applied to monitor the presence of the bacterium in experimental trials. No amplified products indicative of an endemic MJ-PV population were observed in uninoculated treatments indicating other bacterial strains were active in degradation of Microcystin LR, Pilot scale biologically active slow sand filters demonstrated degradation of Microcystin LR irrespective of MJ-PV bacterial inoculation. PCR analysis detected the MJ-PV population at all locations within the sand filters where Microcystin degradation was measured. Despite not observing enhanced degradation of Microcystin LR in inoculated columns compared to uninoculated column, these studies demonstrate the effectiveness of a low-technology water treatment system like biologically active slow sand filters for removal of Microcystins from reticulated water supplies. Crown Copyright (c) 2006 Published by Elsevier Ltd. All rights reserved.
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enzymatic pathway for the bacterial degradation of the cyanobacterial cyclic peptide toxin Microcystin LR
Applied and Environmental Microbiology, 1996Co-Authors: David G Bourne, Gary J Jones, Robert L Blakeley, Alun Jones, Andrew P. Negri, Peter W RiddlesAbstract:An isolated bacterium, identified as a new Sphingomonas species, was demonstrated to contain a novel enzymatic pathway which acted on Microcystin LR, the most common cyanobacterial cyclic peptide toxin. Degradation of Microcystin LR was mediated by at least three intracellular hydrolytic enzymes. The use of classic protease inhibitors allowed (i) the classification of these enzymes into general protease families and (ii) the in vitro accumulation of otherwise transient Microcystin LR degradation products. The initial site of hydrolytic cleavage of the parent cyclic peptide by an enzyme that we designate Microcystinase is at the 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid (Adda)-Arg peptide bond. Two intermediates of Microcystin LR enzymatic degradation have been identified; one is linearized (acyclo-) Microcystin LR, NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-Leu-beta-methylas partate-Arg-OH, and the other is the tetrapeptide NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-OH. The intermediate degradation products were less active than the parent cyclic peptide; the observed 50% inhibitory concentrations for crude chicken brain protein phosphatase were 0.6 nM for Microcystin LR, 95 nM for linear LR, and 12 nM for the tetrapeptide. These linear peptides were nontoxic to mice at doses up to 250 micrograms/kg. Ring opening of the potent hepatotoxin Microcystin LR by bacterial Microcystinase effectively renders the compound nontoxic by dramatically reducing the interaction with the target protein phosphatase.
Seppo Salminen - One of the best experts on this subject based on the ideXlab platform.
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Removal of Microcystin-LR by strains of metabolically active probiotic bacteria
Fems Microbiology Letters, 2007Co-Authors: Sonja Nybom, Seppo Salminen, Jussi MeriluotoAbstract:The ability of specific strains of probiotic bacteria to remove the cyanobacterial peptide toxin Microcystin-LR from aqueous solutions was assessed. Lactobacillus rhamnosus strains GG and LC-705, Bifidobacterium longum 46, Bifidobacterium lactis 420 and Bifidobacterium lactis Bb12 were shown to be the most effective in toxin removal among 11 tested strains. The highest removal percentage of Microcystin-LR was 58.1%, observed with B. lactis Bb12 (toxin concentration 100 μg L−1, 1010 CFU mL−1, 37°C, 24 h). Freshly cultured bacteria were shown to be more efficient in Microcystin removal than lyophilized or nonviable bacteria. Removal of Microcystin-LR was shown to be dependent on both temperature and bacterial concentration. It is concluded that some of the tested strains have good potential in removing Microcystins from aqueous solutions.
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removal of the cyanobacterial toxin Microcystin LR by human probiotics
Toxicon, 2005Co-Authors: Jussi Meriluoto, Lisa Spoof, Carolyn A Haskard, Olli Sjovall, Miguel Gueimonde, Seppo SalminenAbstract:Abstract Three human probiotics, Lactobacillus rhamnosus strains GG and LC-705, and Bifidobacterium lactis strain Bb12, were found to bind the cyanobacterial peptide toxin Microcystin-LR from water solutions. The highest removal percentage was 46%, observed with heat-treated L. rhamnosus strain GG (1010 cells/ml) and a Microcystin-LR concentration of 0.5 μg/ml during an incubation of 7 h at 35 °C.
Peter W Riddles - One of the best experts on this subject based on the ideXlab platform.
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biodegradation of the cyanobacterial toxin Microcystin LR in natural water and biologically active slow sand filters
Water Research, 2006Co-Authors: David G Bourne, Gary J Jones, Robert L Blakeley, Peter W RiddlesAbstract:A bacterium (MJ-PV) previously demonstrated to degrade the cyanobacterial toxin Microcystin LR, was investigated for bioremediation applications in natural water microcosms and biologically active slow sand filters. Enhanced degradation of Microcystin LR was observed with inoculated (1 x 10(6) cell/mL) treatments of river water dosed with Microcystin LR (> 80% degradation within 2 days) compared to uninoculated controls. Inoculation of MJ-PV at lower concentrations (1 x 10(2)-1 x 10(5)cells/mL) also demonstrated enhanced Microcystin LR degradation over control treatments. Polymerase chain reactions (PCR) specifically targeting amplification of 16S rDNA of MJ-PV and the gene responsible for initial degradation of Microcystin LR (mLRA) were successfully applied to monitor the presence of the bacterium in experimental trials. No amplified products indicative of an endemic MJ-PV population were observed in uninoculated treatments indicating other bacterial strains were active in degradation of Microcystin LR, Pilot scale biologically active slow sand filters demonstrated degradation of Microcystin LR irrespective of MJ-PV bacterial inoculation. PCR analysis detected the MJ-PV population at all locations within the sand filters where Microcystin degradation was measured. Despite not observing enhanced degradation of Microcystin LR in inoculated columns compared to uninoculated column, these studies demonstrate the effectiveness of a low-technology water treatment system like biologically active slow sand filters for removal of Microcystins from reticulated water supplies. Crown Copyright (c) 2006 Published by Elsevier Ltd. All rights reserved.
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enzymatic pathway for the bacterial degradation of the cyanobacterial cyclic peptide toxin Microcystin LR
Applied and Environmental Microbiology, 1996Co-Authors: David G Bourne, Gary J Jones, Robert L Blakeley, Alun Jones, Andrew P. Negri, Peter W RiddlesAbstract:An isolated bacterium, identified as a new Sphingomonas species, was demonstrated to contain a novel enzymatic pathway which acted on Microcystin LR, the most common cyanobacterial cyclic peptide toxin. Degradation of Microcystin LR was mediated by at least three intracellular hydrolytic enzymes. The use of classic protease inhibitors allowed (i) the classification of these enzymes into general protease families and (ii) the in vitro accumulation of otherwise transient Microcystin LR degradation products. The initial site of hydrolytic cleavage of the parent cyclic peptide by an enzyme that we designate Microcystinase is at the 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid (Adda)-Arg peptide bond. Two intermediates of Microcystin LR enzymatic degradation have been identified; one is linearized (acyclo-) Microcystin LR, NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-Leu-beta-methylas partate-Arg-OH, and the other is the tetrapeptide NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-OH. The intermediate degradation products were less active than the parent cyclic peptide; the observed 50% inhibitory concentrations for crude chicken brain protein phosphatase were 0.6 nM for Microcystin LR, 95 nM for linear LR, and 12 nM for the tetrapeptide. These linear peptides were nontoxic to mice at doses up to 250 micrograms/kg. Ring opening of the potent hepatotoxin Microcystin LR by bacterial Microcystinase effectively renders the compound nontoxic by dramatically reducing the interaction with the target protein phosphatase.