@article {4879,
	title = {The adsorption of microcystin-LR by natural clay particles},
	journal = {Toxicon},
	volume = {38},
	number = {2},
	year = {2000},
	note = {ISI Document Delivery No.: 257VLTimes Cited: 40Cited Reference Count: 35},
	month = {Feb},
	pages = {303-308},
	type = {Article},
	abstract = {The microcystin cyanobacterial hepatotoxins represent an increasingly severe global health hazard. Sines microcystins are found world wide in drinking water reservoirs concern about the impact on human health has prompted investigations into remedial water treatment methods. This preliminary study investigates the scavenging from water of microcystin-LR by fine-grained particles known to have a high concentration of the clay minerals kaolinite and montmorillonite. The results show that more than 81\% of microcystin-LR can be removed from water by clay material. Thus, microcystin-LR is indeed scavenged from water bodies by fine-grained particles and that this property may offer an effective method of stripping these toxins from drinking water supplies. (C) 1999 Elsevier Science Ltd. All rights reserved.},
	keywords = {BLOOM, cyanobacteria, DECOMPOSITION, DIARRHETIC SHELLFISH TOXINS, ENVIRONMENT, IDENTIFICATION, OKADAIC ACID, OSCILLATORIA-AGARDHII, PROTEIN PHOSPHATASE INHIBITORS, TUMOR PROMOTION},
	isbn = {0041-0101},
	url = {<Go to ISI>://000083803000016},
	author = {Morris, R. J. and Williams, D. E. and Luu, H. A. and Holmes, C. F. B. and Andersen, R. J. and Calvert, S. E.}
}
@article {4158,
	title = {Bioaccumulation and clearance of microcystins from salt water, mussels, Mytilus edulis, and in vivo evidence for covalently bound microcystins in mussel tissues},
	journal = {Toxicon},
	volume = {35},
	number = {11},
	year = {1997},
	note = {ISI Document Delivery No.: YM145Times Cited: 73Cited Reference Count: 48},
	month = {Nov},
	pages = {1617-1625},
	type = {Article},
	abstract = {Over a period of 3 days saltwater mussels, Mytilus edulis, were fed a cyanobacteria, Microcystis aeruginosa, that contained a high concentration of microcystins, The mussels were killed on a periodic basis over the course of 2 months, Mussels were also collected at two sites were high levels of microcystins in tissues had been noted. A strategy based on the chemically unique nature of the C-20 beta-amino acid, (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoi c acid (Adda), portion of the microcystins was used in conjunction with a protein phosphatase (PPase) assay to analyse for both covalently bound microcystins and free microcystins in the mussel tissues, The mussel PPase assay results were compared with the Lemieux oxidation gas chromatography-mass spectrometry (GCMS) analysis. Less than 0.1\% of the total microcystin burden in the mussel tissue was found to be extractable with MeOH. Thus, direct evidence was provided for the existence of covalently bound microcystins in mussel tissues in vivo. The mussels rapidly cleared the covalently bound microcystins when transferred to untreated seawater. Within 4 days the total microcystin burden dropped from a high of 336.9 (+/- 45.8) mu g/g wet tissue to 11.3 (+/- 2.6) mu g/g. After 4 days postexposure until completion of the experiment the total levels remained below the detection limits of the GCMS method, The levels of free microcystins, extracted with MeOH and detected by the PPase assay, fell from 204 ng/g wet tissue to a residual 14 ng/g over a 53 day postexposure period. Presumably the bound microcystin present in the mussel tissue exists as a covalent complex with the PP-1 and PP-2A enzymes. We conclude that in any shellfish monitoring program it is the total tissue microcystin burden that needs to be considered. (C) 1997 Elsevier Science Ltd.},
	keywords = {AERUGINOSA, BLUE-GREEN-ALGAE, cyanobacteria, DIARRHETIC SHELLFISH TOXINS, IDENTIFICATION, LR, OKADAIC ACID, PEPTIDE TOXIN, PROTEIN PHOSPHATASE INHIBITORS, TUMOR PROMOTION},
	isbn = {0041-0101},
	url = {<Go to ISI>://000071033700005},
	author = {Williams, D. E. and Dawe, S. C. and Kent, M. L. and Andersen, R. J. and Craig, M. and Holmes, C. F. B.}
}
@article {3876,
	title = {Cytotoxic peptides hemiasterlin, hemiasterlin A and hemiasterlin B induce mitotic arrest and abnormal spindle formation},
	journal = {Cancer Chemotherapy and Pharmacology},
	volume = {39},
	number = {3},
	year = {1997},
	note = {ISI Document Delivery No.: VZ251Times Cited: 66Cited Reference Count: 17},
	month = {Jan},
	pages = {223-226},
	type = {Article},
	abstract = {Purpose: Hemiasterlin, hemiasterlin A and hemiasterlin B are newly isolated cytotoxic tripeptides with potential as antitumor drugs. We wished to determine their mechanism of cytotoxicity. Methods: We studied their effect on cell survival, cell cycle progression, and microtubule morphology in MCF-7 human mammary carcinoma cells. Results: At the nanomolar concentrations at which they were cytotoxic, the peptides induced arrest in mitotic metaphase. Hemiasterlin A produced abnormal mitotic spindles like those produced by the microtubule inhibitors taxol, nocodazole and vinblastine at low concentrations. At high concentrations hemiasterlin A did not cause microtubule bundling like taxol, but caused microtubule depolymerization like nocodazole and vinblastine. Conclusions: The hemiasterlins probably exert their cytotoxic effect by inhibiting spindle microtubule dynamics.},
	keywords = {CANCER, COLCHICINE SITE, FOSTRIECIN, INHIBITION, microtubules, mitosis, NATURAL-PRODUCTS, OKADAIC ACID, PHOSPHATASE-2A, PODOPHYLLOTOXIN, TAXOL, TUBULIN, VINBLASTINE, VINCA DOMAIN},
	isbn = {0344-5704},
	url = {<Go to ISI>://A1997VZ25100008},
	author = {Anderson, H. J. and Coleman, J. E. and Andersen, R. J. and Roberge, M.}
}
@article {4157,
	title = {Evidence for a covalently bound form of microcystin-LR in salmon liver and dungeness crab larvae},
	journal = {Chemical Research in Toxicology},
	volume = {10},
	number = {4},
	year = {1997},
	note = {ISI Document Delivery No.: WU385Times Cited: 56Cited Reference Count: 55},
	month = {Apr},
	pages = {463-469},
	type = {Article},
	abstract = {The chemically unique nature of the C-20 beta-amino acid (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoi c acid (Adda) portion of the microcystins has been exploited to develop a strategy to analyze for the total microcystin-1R (1; see Figure 1) burden in salmon liver and crab larvae tissues. Lemieux oxidation of microcystin-LR (1) gives 2-methyl-3-methoxy-4-phenylbutanoic acid (2), a unique marker for the presence of microcystins. The butanoic acid 2 can be isolated and detected by GC/MS from the livers of Atlantic salmon that received an ip injection of microcystin-1R (1) and from tissues of wild-caught crab larvae. The Lemieux oxidation-GC/MS results are compared with those from MeOH extraction-PPase analysis. Only similar to 24\% of the total microcystin-1R (1) burden in salmon liver tissue is found to be extractable with MeOH. Similarly, the Lemieux oxidation-GC/MS method detected 10 000-fold greater microcystin concentrations in Cypress Island Dungeness crab larvae than did the MeOH extraction-PPase method. The disparity in microcystin concentrations measured by the two methods is taken as direct evidence for the existence of covalently bound microcystins in vivo.},
	keywords = {BLUE-GREEN-ALGAE, CYCLIC, DIARRHETIC SHELLFISH TOXINS, DIHYDROMICROCYSTIN-LR, HEPATOCELLULAR, OKADAIC ACID, PEPTIDE TOXIN, PROTEIN PHOSPHATASE INHIBITORS, RAT-LIVER, TISSUE DISTRIBUTION, TUMOR PROMOTION, UPTAKE},
	isbn = {0893-228X},
	url = {<Go to ISI>://A1997WU38500017},
	author = {Williams, D. E. and Craig, M. and Dawe, S. C. and Kent, M. L. and Holmes, C. F. B. and Andersen, R. J.}
}
@article {3640,
	title = {Molecular mechanisms underlying the interaction of motuporin and microycystins with type-1 and type-2A protein phosphatases},
	journal = {Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire},
	volume = {74},
	number = {4},
	year = {1996},
	note = {ISI Document Delivery No.: VX367Times Cited: 61Cited Reference Count: 35},
	pages = {569-578},
	type = {Article},
	abstract = {Heptapeptide microcystin and pentapeptide motuporin (nodularin-V) are equipotent inhibitors of type-1 and type-2A protein phosphatase catalytic subunits (PP-1c and PP-2Ac). Herein we describe elucidation of the molecular mechanisms involved in the interaction of these structurally similar hepatotoxins with PP-1c/PP-2Ac and identification of an important functional difference between their mode of interaction with these enzymes. Microcystin-LR, microcystin-LA and microcystin-LL were found to interact with PP-2Ac and PP-1c by a two-step mechanism involving rapid binding and inactivation of the protein phosphatase (PPase) catalytic subunit, followed by a slower covalent interaction (within hours). Covalent adducts comprising PPase-toxin complexes were separated from free PPase by C-18 reverse-phase liquid chromatography, thus allowing the time course of covalent adduct formation to be quantitated. In contrast to microcystins, motuporin (nodularin-V) and nodularin-R were unable to form covalent complexes with either PP-1c or PP-2Ac even after 96 h incubation. Specific reduction of microcystin-LA to dihydromicrocystin-LA abolished the ability of the toxin to form a covalent adduct with PP-2Ac. Specific methyl esterification of the single Glu residue in microcystin-LR rendered this toxin inactive as a PPase inhibitor and abolished subsequent formation of a covalent adduct. Our data indicate that inactivation of PP-2Ac/PP-1c by microcystins precedes covalent modification of the PPases via a Michael addition reaction between a nucleophilic phosphatase residue and Mdha in the heptapeptide toxin. In contrast, following rapid inactivation of PP-2Ac/PP-1c by motuporin, the equivalent N-methyldehydrobutyrine residue in this toxin is unreactive and does not form a covalent bond with the PPases. These results are consistent with structural data for (i) the NMR solution structures of microcystin-LR and motuporin, which indicate a striking difference in the relative positions of their corresponding dehydroamino acids in the toxin peptide backbone, and (ii) X-ray crystallographic data on an inactive complex between PP-1c and microcystin-LR, which show a covalent bond between Cys-273 and the bound toxin.},
	keywords = {BLUE-GREEN-ALGAE, CATALYTIC SUBUNIT, cyanobacteria, IDENTIFICATION, MICROCYSTIN-LR, microcystins, motuporin, nodularin, OKADAIC ACID, PHOSPHORYLATION, POTENT INHIBITOR, PROTEIN, PROTEIN PHOSPHATASES, RAT-LIVER, TOXINS},
	isbn = {0829-8211},
	url = {<Go to ISI>://A1996VX36700017},
	author = {Craig, M. and Luu, H. A. and McCready, T. L. and Williams, D. and Andersen, R. J. and Holmes, C. F. B.}
}
@article {2753,
	title = {IDENTIFICATION OF PROTEIN PHOSPHATASE INHIBITORS OF THE MICROCYSTIN CLASS IN THE MARINE-ENVIRONMENT},
	journal = {Toxicon},
	volume = {31},
	number = {11},
	year = {1993},
	note = {ISI Document Delivery No.: MM430Times Cited: 38Cited Reference Count: 28},
	month = {Nov},
	pages = {1407-1414},
	type = {Article},
	abstract = {Toxins produced by marine phytoplankton represent a severe global health hazard to humans that eat seafood and are also responsible for massive natural fish kills in specialized bloom situations. Tumour-promoting hepatotoxins from the freshwater microcystin/nodularin class were identified in Northeastern Pacific Ocean, Eastern Canadian and European mussels for the first time. These hepatotoxins were detected at biologically active levels up to three-fold higher than accepted quarantine levels for the diarrhetic shellfish toxin okadaic acid (OA), based on their activity (in microcystin-LR equivalent units) in a liquid chromatography (LC)-linked protein phosphatase bioassay. The presence of microcystins/nodularins in oceanic shellfish identifies a potentially novel class of intoxication which is also prevalent in other forms of marine aquatic life, namely sponges and fish. The widespread presence of prokaryotic microcystins and nodularins in the marine environment may be indicative of the importance of signal transduction pathways involving potent inhibition of protein phosphatases in early marine eukaryotes.},
	keywords = {DIARRHETIC SHELLFISH TOXINS, HIGHER-PLANTS, LR, nodularin, OKADAIC ACID, POTENT, TYPE-1},
	isbn = {0041-0101},
	url = {<Go to ISI>://A1993MM43000005},
	author = {Chen, D. Z. X. and Boland, M. P. and Smillie, M. A. and Klix, H. and Ptak, C. and Andersen, R. J. and Holmes, C. F. B.}
}
@article {2702,
	title = {NEW NATURAL-PRODUCTS FROM MARINE-INVERTEBRATES},
	journal = {Gazzetta Chimica Italiana},
	volume = {123},
	number = {6},
	year = {1993},
	note = {ISI Document Delivery No.: LL566Times Cited: 3Cited Reference Count: 457TH INTERNATIONAL SYMP ON MARINE NATURAL PRODUCTS ( VII MANAPRO )JUL 05-10, 1992CAPRI, ITALY},
	month = {Jun},
	pages = {293-299},
	type = {Proceedings Paper},
	abstract = {Extracts of marine invertebrates collected in British Columbia and Papua New Guinea have been screened for the presence of cytotoxic and enzyme modulatory metabolites. Chemical examination of several active extracts has resulted in the identification of a number of novel natural products. These include: contignasterol, 2, a steroid having a cis C/D ring junction; pseudaxinellin, 5, a cyclic heptapeptide; trididemnic acids A, 7, and B, 8, two aromatic alkaloids from a tunicate; the rubrolides A, 13, to H, 20, a family of highly halogenated tunicate metabolites; and motuporin, 22, a cyclic pentapeptide that is the first marine representative of the microcystin class of hepatotoxic and tumor-promoting cyclic peptides. Microcystin LR has been found in marine shellfish for the first time and it has been implicated as the cause of a severe liver disease that occurs in netpen reared salmon in British Columbia.},
	keywords = {METABOLITES, microcystin, OKADAIC ACID, PEPTIDE, POTENT, SPONGE THEONELLA SP, TUMOR PROMOTER},
	isbn = {0016-5603},
	url = {<Go to ISI>://A1993LL56600001},
	author = {Andersen, R. J. and Burgoyne, D. L. and Williams, D. E. and Kong, F. M. and De Silva, E. D. and Miao, S. C. and Allen, T. M. and Holmes, C. F. B. and Chen, D. and Kent, M.}
}
