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Phycotoxins: chemistry, mechanisms of action and shellfish poisoning

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Molecular, Clinical and Environmental Toxicology

Part of the book series: Experientia Supplementum ((EXS,volume 100))

Abstract

Phycotoxins are natural metabolites produced by micro-algae. Through accumulation in the food chain, these toxins may concentrate in different marine organisms, including filter-feeding bivalves, burrowing and grazing organisms, herbivorous and predatory fish. Human poisoning due to ingestion of seafood contaminated by phycotoxins has occurred in the past, and harmful algal blooms (HABs) are naturally occurring events. Still, we are witnessing a global increase in HABs and seafood contaminations, whose causative factors are only partially understood. Phycotoxins are small to medium-sized natural products and belong to many different groups of chemical compounds. The molecular mass ranges from ≈300 to over 3000 Da, and the compound classes represented include amino acids, alkaloids and polyketides. Each compound group typically has several main compounds based on the same or similar structure. However, most groups also have several analogues, which are either produced by the algae or through metabolism in fish or shellfish or other marine organisms. The different phycotoxins have distinct molecular mechanisms of action. Saxitoxins, ciguatoxins, brevetoxins, gambierol, palytoxins, domoic acid, and, perhaps, cyclic imines, alter different ion channels and/or pumps at the level of the cell membrane. The normal functioning of neuronal and other excitable tissues is primarily perturbed by these mechanisms, leading to adverse effects in humans. Okadaic acid and related compounds inhibit serine/threonine phosphoprotein phosphatases, and disrupt major mechanisms controlling cellular functions. Pectenotoxins bind to actin filaments, and alter cellular cytoskeleton. The precise mechanisms of action of yessotoxins and azaspiracids, in turn, are still undetermined. The route of human exposure to phycotoxins is usually oral, although living systems may become exposed to phycotoxins through other routes. Based on recorded symptoms, the major poisonings recognized so far include paralytic, neurotoxic, amnesic, diarrheic shellfish poisonings, ciguatera, as well as palytoxin and azaspiracid poisonings.

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References

  1. Tachibana K, Scheuer PJ, Tsukitani Y, Kikuchi H, Van Engen D, Clardy J, Gopichand Y, Schmitz FJ (1981) Okadaic acid, a cytotoxic polyether from two marine sponges of the genus Halichondria. J Am Chem Soc 103: 2469–2471

    Article  CAS  Google Scholar 

  2. Takemoto T, Daigo K (1958) Constituents of Chondria armata. Chem Pharm Bull 6: 578–580

    CAS  Google Scholar 

  3. Daigo K (1959) Constituents of Chondria armata. I. Detection of the anthelmintic constituents. Yakugaku Zasshi 79: 350–353

    CAS  Google Scholar 

  4. Daigo K (1959) Constuents of Chondria armata. II. Isolation of an anthelmintic constituent. Yakugaku Zasshi 79: 353–356

    CAS  Google Scholar 

  5. Takemoto T, Daigo K (1960) Über die Inhaltsstoffe von Chondria armata und ihre pharmakologische Wirkung. Arch Pharm 293: 627–633

    Article  CAS  PubMed  Google Scholar 

  6. Moore RE, Scheuer PJ (1971) Palytoxin: A new marine toxin from a coelenterate. Science 172: 495–498

    Article  CAS  PubMed  Google Scholar 

  7. Hallegraeff GM (2004) Harmful algal blooms: A global overview. In: GM Hallegraeff, DM Anderson, AD Cembella (eds): Manual on Harmful Marine Microalgae, 2nd edn. UNESCO, Paris, 25–49

    Google Scholar 

  8. Gallitelli M, Ungaro N, Addante LM, Gentiloni N, Sabbà C (2005) Respiratory illness as a reaction to tropical algal blooms occurring in a temperate climate. J Am Med Assoc 293: 2599–2600

    Article  CAS  Google Scholar 

  9. Durando P, Ansaldi F, Oreste P, Moscatelli P, Marensi L, Grillo C, Gasparini R, Icardi G (2007) Collaborative Group for Ligurian Syndromic Algal Surveillance. Eur Surveill 12: E070607.1

    CAS  Google Scholar 

  10. Worm B, Barbier EB, Beaumont N, Duffy JE, Folke C, Halpern BS, Jackson JB, Lotze HK, Micheli F, Palumbi SR, Sala E, Selkoe KA, Stachowicz JJ, Watson R (2006) Impact of biodiversity loss on ocean ecosystem services. Science 314: 787–790

    Article  CAS  PubMed  Google Scholar 

  11. Virchow R (1885) Über die Vergiftungen durch Miesmuscheln in Wilhelmshaven. Berl Klin Wochenschr 48: 1–2

    Google Scholar 

  12. Wolff M (1887) Ueber das erneute Vorkommen von giftigen Miessmuscheln in Wilhelmshaven. Virchows Arch 110: 376–380

    Article  Google Scholar 

  13. Sommer H, Heyer KF (1937) Paralytic shellfish poisoning. AMA Arch Path 24: 560–598

    CAS  Google Scholar 

  14. Onoue Y, Noguchi T, Maruyama J, Hashimoto K, Seto H (1931) Properties of two toxins newly isolated from oysters. J Agric Food Chem 2: 420–423

    Google Scholar 

  15. Schantz EJ, Mold JD, Stanger DW, Shavel J, Riel FJ, Bowden JP, Lynch JM, Wyler RS, Riegel B, Sommer H (1957) Paralytic shellfish poison. VI. A procedure for the isolation and purification of the poison from toxic clam and mussel tissue. J Am Chem Soc 79: 5230–5235

    Article  CAS  Google Scholar 

  16. Schantz EJ, McFarren EF, Schafer ML, Lewis KH (1958) Purified shellfish poison for bioassay standardization. J Assoc Off Anal Chem 41: 160–168

    CAS  Google Scholar 

  17. Wong JL, Oesterlin R, Rapoport H (1971) The structure of saxitoxin. J Am Chem Soc 93: 1238–1239

    Google Scholar 

  18. Quilliam MA, Wright JLC (1989) The amnesic shellfish poisoning mystery. Anal Chem 61: 1053–1060

    Article  Google Scholar 

  19. Yasumoto T, Oshima Y, Yamaguchi M (1978) Occurrence of a new type of shellfish poisoning in the Tohoku district. Bull Jpn Soc Sci Fish 44: 1249–1255

    Google Scholar 

  20. Satake M, Ofuji K, Naoki H, James KJ, Furey A, McMahon T, Silke J, Yasumoto T (1998) Azaspiracid, a new marine toxin having unique spiro ring assemblies, isolated from Irish mussels, Mytilus edulis. J Am Chem Soc 120: 9967–9968

    Article  CAS  Google Scholar 

  21. FAO. Report of the Joint FAO/IOC/WHO ad hoc Expert Consultation on Biotoxins in Bivalve Molluscs, Oslo, Norway, Sept. 26–30, 2004. Available at: ftp://ftp.fao.org/es/esn/food/biotoxin_report_en.pdf (accessed 5 June 2009)

    Google Scholar 

  22. Dell’Aversano C, Eaglesham GK, Quilliam MA (2004) Analysis of cyanobacterial toxins by hydrophilic interaction liquid chromatography-mass spectrometry. J Chromatogr A 1028: 155–164

    Article  PubMed  CAS  Google Scholar 

  23. Dell’Aversano C, Walter JA, Burton IW, Stirling DJ, Fattorusso E, Quilliam MA (2008) Isolation and structure elucidation of new and unusual saxitoxin analogues from mussels. J Nat Prod 71: 1518–1523

    Article  PubMed  CAS  Google Scholar 

  24. Hall S, Reichaedt PB (1984) Cryptic paralytic shellfish toxins. In: EP Regalis (ed.): Seafood Toxins. American Chemical Society, Washington DC, 113–123

    Chapter  Google Scholar 

  25. Harada T, Oshima Y, Yasumoto T (1984) Assessment of potential activation of gonyautoxin V in the stomach of mice and rats. Toxicon 22: 476–478

    Article  CAS  PubMed  Google Scholar 

  26. Association of Official Analytical Chemists (2005) Offial Method 959.08. Paralytic shellfish poison, biological method. In: AOAC Official Methods of Analysis, 18th edn., AOAC Gaithersburg, USA, 79–80

    Google Scholar 

  27. Oshima Y (1995) Postcolumn derivatization liquid chromatographic method for paralytic shellfish toxins. J AOAC Int 78: 528–532

    CAS  Google Scholar 

  28. Lawrence JF, Niedzwiadek B, Menard C (2004) Quantitative determination of paralytic shellfish poisoning toxins in shellfish using prechromatographic oxidation and liquid chromatography with fluorescence detection: Interlaboratory study. J AOAC Int 87: 83–100

    CAS  PubMed  Google Scholar 

  29. Association of Official Analytical Chemists (2005) Off. Method 2005.06. Quantitative determination of paralytic shellfish poisoining toxins in shellfish using prechromatographic oxidation and liquid chromatography with fluorescence detection. In: AOAC Official Methods of Analysis, 18th end., AOAC, Gaithersburg, USA, 81–82

    Google Scholar 

  30. Dell’Aversano C, Hess P, Quilliam MA (2005) Hydrophilic interaction liquid chromatographymass spectrometry for the analysis of paralytic shellfish poisoning (PSP) toxins. J Chromatogr A 1081: 190–201

    Article  PubMed  CAS  Google Scholar 

  31. Quilliam MA, Hess P, Dell’Aversano C (2001) Recent developments in the analysis of phycotoxins by liquid chromatography — mass spectrometry. In: WJ De Koe, RA Samson, HP Van Egmond, J Gilbert, M Sabino (eds): Mycotoxins and Phycotoxins in Perspective at the Turn of the Millenium, W.J. de Koe, Wageningen, 383–391

    Google Scholar 

  32. Walter JA, Leek DM, Falk M (1992) NMR study of the protonation of domoic acid. Can J Chem 70: 1156–1161

    Article  CAS  Google Scholar 

  33. Maeda M, Kodama T, Tanaka T, Yoshizumi H, Takemoto T, Nomoto K, Fujita T (1986) Structures of isodomoic acids A, B and C, novel insecticidal amino acids from the red alga Chondria armata. Chem Pharm Bull 34: 4892–4895

    CAS  Google Scholar 

  34. Maeda M, Kodama T, Tanaka T, Yoshizumi H, Takemoto T, Nomoto K, Fujita T (1987) Structures of domoilactone A and B, novel amino acids from the red alga, Chondria armata. Tetrahedron Lett 28: 633–636

    Article  CAS  Google Scholar 

  35. Wright JLC, Falk M, McInnes AG, Walter JA (1990) Identification of isodomoic acid D and two new geometrical isomers of domoic acid in toxic mussels. Can J Chem 68: 22–25

    Article  CAS  Google Scholar 

  36. Walter JA, Falk M, Wright JLC (1994) Chemistry of the shellfish toxin domoic acid: Characterization of related compounds. Can J Chem 72: 430–436

    Article  CAS  Google Scholar 

  37. Zaman L, Arakawa O, Shimosu A, Onoue Y, Nishio S, Shida Y, Noguchi T (1997) Two new isomers of domoic acid from a red alga, Chondria armata. Toxicon 35: 205–212

    Article  CAS  PubMed  Google Scholar 

  38. Holland PT, Selwood AI, Mountford DO, Wilkins AL, McNabb P, Rhodes LL, Doucette GJ, Mikulski CM, King KL (2005) Isodomoic acid C, an unusual amnesic shellfish poisoning toxin from Pseudo-nitzschia australis. Chem Res Toxicol 18: 814–816

    Article  CAS  PubMed  Google Scholar 

  39. Ramsdell JS (2007) The molecular and integrative basis to domoic acid toxicity. In: LM Botana (ed.): Chemistry and Pharmacology of Marine Toxins, Blackwell Publishing, Oxford, 223–250

    Google Scholar 

  40. Quilliam MA, Xie M, Hardstaff WR (1995) A rapid extraction and cleanup procedure for the liquid chromatographic determination of domoic acid in unsalted seafood. J AOAC Int 78: 543–554

    CAS  Google Scholar 

  41. Hess P, Morris S, Stobo LA, Brown NA, McEvoy JDG, Kennedy G, Young PB, Slattery D, McGovern E, McMahon T, Gallacher S (2005) LC-UV and LC-MS methods for the determination of domoic acid. TrAC — Trends Anal Chem 24: 358–367

    Article  CAS  Google Scholar 

  42. McCarron P, Hess P (2006) Tissue distribution and effects of heat treatments on the content of domoic acid in blue mussels, Mytilus edulis. Toxicon 47: 473–479

    Article  CAS  PubMed  Google Scholar 

  43. McCarron P, Burrell S, Hess P (2007) Effect of addition of antibiotics and an antioxidant, on the stability of tissue reference materials for domoic acid, the amnesic shellfish poison. Anal Bioanal Chem 387: 2495–2502

    Article  CAS  PubMed  Google Scholar 

  44. Twiner MJ, Rehmann N, Hess P, Doucette GJ (2008) Azaspiracid shellfish poisoning: A review on the ecology, chemistry, toxicology and human health impacts. Marine Drugs 6: 39–74

    CAS  PubMed  Google Scholar 

  45. Taleb H, Vale P, Amanhir R, Benhadouch A, Sagou R, Chafik A (2006) First detection of azaspiracids in North West Africa. J Shell Res 25: 1067–1071

    Google Scholar 

  46. Ueoka R, Ito A, Izumikawa M, Maeda S, Takagi M, Shin-ya K, Yoshida M, van Zoest RWM, Matsunaga S (2009) Isolation of azaspiracid-2 from a marine sponge Echinoclathria sp. as a potent cytotoxin. Toxicon 53: 680–684

    Article  CAS  PubMed  Google Scholar 

  47. Hess P, Butter T, Petersen A, Silke J, McMahon T (2009) Performance of the EU harmonised mouse bioassay for lipophilic toxins for the detection of azaspiracids in naturally contaminated mussel (Mytilus edulis) hepatopancreas tissue homogenates characterised by liquid chromatography coupled to tandem mass spectrometry. Toxicon 53: 713–722

    Article  CAS  PubMed  Google Scholar 

  48. Alfonso C, Rehmann N, Hess P, Alfonso A, Wandscheer C, Abuin M, Vale C, Otero P, Vieytes M, Botana LM (2008) Evaluation of various pH and temperature conditions on the stability of azaspiracids, and their importance in preparative isolation and toxicological studies. Anal Chem 80: 9672–9680

    Article  CAS  PubMed  Google Scholar 

  49. Nicolaou K, Chen D, Li Y_ Qian W, Ling T, Vyskocil S, Koftis T, Govindasamy M, Uesaka N (2003) Total synthesis of the proposed azaspiracid-1 structure, part 2: Coupling of the C1–C20, C21–C27, and C28–C40 fragments and completion of the synthesis, Angew Chem 42: 3649–3653

    Article  CAS  Google Scholar 

  50. Nicolaou K, Li, Uesaka N, Koftis T, Byskocil S, Ling T, Govindasamy M, Qian W, Bernal F, Chen D (2003) Total synthesis of the proposed azaspiracid-1 structure, part 1: Construction of the enantiomerically pure C1–C20, C21–C27, and C28–C40 fragments. Angew Chem 42: 3643–3648

    Article  CAS  Google Scholar 

  51. Nicolaou KC, Vyskocil S, Koftis TV, Yamada YM, Ling T, Chen D, Tang W, Petrovic G, Frederick M, Li Y, Satake M (2004) Structural revision and total synthesis of azaspiracid-1, part 1: Intelligence gathering and tentaive proposal. Angew Chem Int Ed 116: 4412–4418

    Article  Google Scholar 

  52. Nicolaou KC, Koftis T, Vyskocil S, Petrovic G, Ling T, Yamada M, Tang W, Frederick M (2004) Structural revision and total synthesis of azaspiracid-1, part 2: Definition of the ABCD domain and total synthesis. Angew Chem Int Ed 116: 4418–4424

    Article  Google Scholar 

  53. Rehmann N, Hess P, Quilliam MA (2008) Discovery of new analogs of the marine biotoxin azaspiracid in blue mussels (Mytilus edulis) by ultra performance liquid chromatography-tandem mass spectrometry. Rapid Commun Mass Spectrom 22: 549–558

    Article  CAS  PubMed  Google Scholar 

  54. Krock B, Tillmann U, John U, Cembella AD (2009) Characterization of azaspiracids in plankton size-fractions and isolation of an azaspiracid-producing dinoflagellate from the North Sea. Harmful Algae 8: 254–263

    Article  CAS  Google Scholar 

  55. Tillmann U, Elbrachter M, Krock B, John U, Cembella A (2009) Azadinium spinosum gen. et sp nov (Dinophyceae) identified as a primary producer of azaspiracid toxins. Eur J Phycol 44: 63–79

    Article  CAS  Google Scholar 

  56. McMahon T, Silke J (1996) Winter toxicity of unknown aetiology in mussels. Harmful Algal News 14: 2

    Google Scholar 

  57. Hess P, Nguyen L, Aasen J, Keogh M, Kilcoyne J, McCarron P, Aune T (2005) Tissue distribution, effects of cooking and parameters affecting the extraction of azaspiracids from mussels, Mytïlus edulis, prior to analysis by liquid chromatography coupled to mass spectrometry. Toxicon 46: 62–71

    Article  CAS  PubMed  Google Scholar 

  58. McCarron P, Kilcoyne J, Miles CO, Hess P (2009) Formation of azaspiracid-3,-4,-6, and-9 via decarboxylation of carboxyazaspiracid metabolites from shellfish. J Agric Food Chem 57: 160–169

    Article  CAS  PubMed  Google Scholar 

  59. Ofuji K, Satake M, McMahon T, James KJ, Naoki H, Oshima Y, Yasumoto T (2001) Structures of azaspiracid analogs, azaspiracid-4 and azaspiracid-5, causative toxins of azaspiracid poisoning in Europe. Biosci Biotechnol Biochem 65: 740–742

    Article  CAS  PubMed  Google Scholar 

  60. Ito E, Frederick MO, Koftis TV, Tang W, Petrovic G, Ling T, Nicolaou KC (2006) Structure toxicity relationships of synthetic azaspiracid-1 and analogs in mice. Harmful Algae 5: 586–591

    Article  CAS  Google Scholar 

  61. Yasumoto T, Oshima Y, Sugarawa W, Fukuyo Y, Oguri H, Igarashi T, Fujita N (1980) Identification of Dinophysis fortii as the causative organism of diarrhetic shellfish poisoning. Bull Jpn Soc Sci Fish 46: 1405–1411

    Google Scholar 

  62. Kumagai M, Yanagi T, Murata M, Yasumoto T, Kat M, Lassus P, Rodriguez-Vazquez JA (1986) Okadaic acid as the causative toxin of diarrhetic shellfish poisoning in Europe. Agric Biol Chem 50: 2853–2857

    CAS  Google Scholar 

  63. Hu T, Doyle J, Jackson D, Marr J, Nixon E, Pleasance S, Quilliam MA, Walter JA, Wright JLC (1992) Isolation of a new diarrhetic shellfish poison from Irish mussels. J Chem Soc Chem Commun 39–41

    Google Scholar 

  64. Swanson K, Villareal T, Campbell L (2008) The 2008 DSP event along the Texas coast: Detection and observations. Poster presentation at the 122nd AOAC Annual Meeting and Exposition, 21–25 September 2008, Dallas, TX

    Google Scholar 

  65. McCarron P, Kilcoyne J, Hess P (2008) Effects of cooking and heat treatment on concentration and tissue distribution of okadaic acid and dinophysistoxin-2 in mussels (Mytilus edulis). Toxicon 51: 1081–1089

    Article  CAS  PubMed  Google Scholar 

  66. Yasumoto T, Murata M, Lee JS, Torigoe K (1989) Polyether toxins produced by dinoflagellates. In: S Natori, K Hashimoto, Y Ueno (eds): Mycotoxins and Phycotoxins’ 88, Elsevier, Amsterdam, 375–382

    Google Scholar 

  67. Hu TM, Curtis JM, Oshima Y, Quilliam MA, Walter JA, Watsonwright WM, Wright JLC (1995) Spirolide-B and spirolides-D, 2 novel macrocycles isolated from the digestive glands of shellfish. J Chem Soc Chem Comm 2159–2161

    Google Scholar 

  68. Vale P (2007) Chemistry of diarrhetic shellfish poisoning toxins. In: LM Botana (ed.): Chemistry and Pharmacology of Marine Toxins, Blackwell Publishing, Oxford, 211–221

    Google Scholar 

  69. Yasumoto T, Murata M, Oshima Y, Sano M (1985) Diarrhetic shellfish toxins. Tetrahedron 41: 1019–1025

    Article  CAS  Google Scholar 

  70. Yanagi T, Murata M, Torigoe K, Yasumoto T (1989) Biological activities of semisynthetic analogs of dinophysistoxin-3, the major diarrhetic shellfish toxin. Agric Biol Chem 53: 525–529

    CAS  Google Scholar 

  71. Britton R, Roberge M, Brown C, van Soest R, Andersen RJ (2003) New okadaic acid analogues from the marine sponge Merriamum oxeato and their effect on mitosis. J Nat Prod 66, 838–843

    Article  CAS  PubMed  Google Scholar 

  72. Torgersen T, Miles CO, Rundberget T, Wilkins AL (2008) New esters of okadaic acid in seawater and blue mussels (Mytilus edulis). J Agric Food Chem 56: 9628–9635

    Article  CAS  PubMed  Google Scholar 

  73. Lee JS, Igarashi T, Fraga S, Dahl E, Hovgaard P, Yasumoto T (1989) Determination of diarrhetic shellfish toxins in various dinoflagellate species. J Appl Physiol 1: 147–152

    Google Scholar 

  74. EFSA (2008) Marine biotoxins in shellfish — Okadaic acid and analogues, Scientific Opinion of the Panel on Contaminants in the Food Chain. EFSA J 589: 1–62

    Google Scholar 

  75. Aune T, Larsen S, Aasen J, Rehmann N, Satake M, Hess P (2007) Relative toxicity of dinophysistoxin-2 (DTX-2) compared with okadaic acid, based on acute intraperitoneal toxicity in mice. Toxicon 49: 1–7

    Article  CAS  PubMed  Google Scholar 

  76. Miles CO (2007) Pectenotoxins. In: LM Botana (ed.): Chemistry and Pharmacology of Marine Toxins, Blackwell Publishing, Oxford, 159–186

    Google Scholar 

  77. Suzuki T, Igarashi T, Ichimi K, Watai M, Suzuki M, Ogiso E, Yasumoto T (2005) Kinetics of diarrhetic shellfish poisoning toxins, okadaic acid, dinophysistoxin-1, pectenotoxin-6 and yessotoxin in scallops Patinopecten yessoensis. Fish Sci 71: 948–955

    Article  CAS  Google Scholar 

  78. Miles CO, Wilkins AL, Munday R, Dines MH, Hawkes AD, Briggs LR, Sandvik M, Jensen DJ, Cooney JM, Holland PT, Quilliam MA, MacKenzie AL, Beuzenberg V, Towers NR (2004) Isolation of pectenotoxin-2 from Dinophysis acuta and its conversion to pectenotoxin-2 seco acid, and preliminary assessment of their acute toxicities. Toxicon 43: 1–9

    Article  CAS  PubMed  Google Scholar 

  79. Wilkins AL, Rehmann N, Torgersen T, Rundberget T, Keogh M, Petersen D, Hess P, Rise F, Miles CO (2006) Identification of fatty acid esters of pectenotoxin-2 seco acid in blue mussels (Mytilus edulis) from Ireland. J Agric Food Chem 54: 5672–5678

    Article  CAS  PubMed  Google Scholar 

  80. Ito E, Suzuki T, Oshima Y, Yasumoto T (2008) Studies of diarrhetic activity on pectenotoxin-6 in the mouse and rat. Toxicon 51: 707–716

    Article  CAS  PubMed  Google Scholar 

  81. Hess P, Aasen JB (2007) Chemistry, origins and distribution of yessotoxin and its analogues. In: LM Botana (ed.): Chemistry and Pharmacology of Marine Toxins, Blackwell Publishing, Oxford, 187–202

    Google Scholar 

  82. Murata M, Kumagai M, Lee JS, Yasumoto T (1987) Isolation and structure of yessotoxin, a novel polyether compound implicated in diarrhetic shellfish poisoning. Tetrahedron Lett 28: 5869–5872

    Article  CAS  Google Scholar 

  83. Aune T, Sorby R, Yasumoto T, Ramstad H, Landsverk T (2002) Comparison of oral and intraperitoneal toxicity of yessotoxin towards mice. Toxicon 40: 77–82

    Article  CAS  PubMed  Google Scholar 

  84. Tubaro A, Sosa S, Carbonatto M, Altinier G, Vita F, Melato M, Satake M, Yasumoto T (2003) Oral and intraperitoneal acute toxicity studies of yessotoxin and homoyessotoxins in mice. Toxicon 41: 783–792

    Article  CAS  PubMed  Google Scholar 

  85. Tubaro A, Sosa S, Altinier G, Soranzo MR, Satake M, Della Loggia R, Yasumoto T (2004) Short-term oral toxicity of homoyessotoxins, yessotoxin and okadaic acid in mice. Toxicon 43: 439–445

    Article  CAS  PubMed  Google Scholar 

  86. Ciminiello P, Dell’Aversano C, Fattorusso E, Forino M, Magno S, Guerrini F, Pistocchi R, Boni L (2003) Complex yessotoxins profile in Protoceratium reticulatum from north-western Adriatic sea revealed by LC-MS analysis. Toxicon 42: 7–14

    Article  CAS  PubMed  Google Scholar 

  87. Samdal IA, Naustvoll LJ, Olseng CD, Briggs LR, Miles CO (2004) Use of ELISA to identify Protoceratium reticulatum as a source of yessotoxin in Norway. Toxicon 44: 75–82

    Article  CAS  PubMed  Google Scholar 

  88. Satake M, MacKenzie L, Yasumoto T (1997) Hentification of Protoceratium reticulatum as the biogenetic origin of yessotoxin. Nat Toxins 5: 164–167

    Article  CAS  PubMed  Google Scholar 

  89. Satake M, Ichimura T, Sekiguchi K, Yoshimatsu S, Oshima Y (1999) Confirmation of yessotoxin and 45,46,47-trinoryessotoxin production by Protoceratium reticulatum collected in Japan. Nat Toxins 7: 147–150

    Article  CAS  PubMed  Google Scholar 

  90. Draisci R, Ferretti E, Palleschi L, Marchiafava C, Poletti R, Milandri A, Ceredi A, Pompei M (1999) High levels of yessotoxin in mussels and presence of yessotoxin and homoyessotoxin in dinoflagellates of the Adriatic Sea. Toxicon 37: 1187–1193

    Article  CAS  PubMed  Google Scholar 

  91. Rhodes L, McNabb P, de Salas M, Briggs L, Beuzenberg V, Gladstone M (2006) Yessotoxin production by Gonyaulax spinifera. Harmful Algae 5: 148–155

    Article  CAS  Google Scholar 

  92. Draisci R, Lucentini L, Mascioni A (2000) Petenotoxins and yessotoxins: Chemistry, toxicology, pharmacology, and analysis. In: Botana, LM (ed.): Seafood and Freshwater Toxins: Pharmacology, Physiology, and Detection, Marcel Dekker, New York, 289–324

    Google Scholar 

  93. Finch S, Wilkins A. Hawkes A, Jensen D, MacKenzie L, Beuzenberg V, Quilliam M, Olseng C, Samdal I, Aasen J, Selwood AI, Cooney JM, Sandvik M, Miles CO (2005) Isolation and identification of (44-R,S)-44,55, dihydroxyyessotoxin from Protoceratium reticulatum, and its occurrence in extracts of shellfish from New Zealand, Norway and Canada Toxicon 46: 160–170

    Article  CAS  PubMed  Google Scholar 

  94. Miles CO, Samdal IA, Aasen JAB, Jensen DJ, Quilliam M, Petersen D, Briggs LM, Wilkins AL, Rise F, Cooney JM, MacKenzie AL (2005) Evidence of numerous analogs of yessotoxin in Protoceratium reticulatum. Harmful Algae 4: 1075–1091

    Article  CAS  Google Scholar 

  95. Satake M, Tubaro A, Lee JS, Yasumoto T (1997) Two new analogs of yessotoxin, homoyessotoxin and 4,5-hydroxyhomoyessotoxin, isolated from mussels of the Adriatic Sea. Nat Toxins 5: 107–110

    Article  CAS  PubMed  Google Scholar 

  96. Miles CO, Wilkins AL, Jensen DJ, Cooney JM, Quilliam MA, Aasen J, Mackenzie AL (2004) Isolation of 41a-homoyessotoxin and the identification of 9-methyl-41a-homoyessotoxin and nor-ring A-yessotoxin from Protoceratium reticulatum. Chem Res Toxicol 17: 1414–1422

    Article  CAS  PubMed  Google Scholar 

  97. Miles CO, Wilkins AL, Hawkes AD, Selwood AI, Jensen DJ, Munday R, Cooney, JM, Beuzenberg V (2005) Polyhydroxylated amide analogs of yessotoxin from Protoceratium reticulatum. Toxicon 45: 61–71

    Article  CAS  PubMed  Google Scholar 

  98. Ferrari S, Ciminiello P, Dell’Aversano C, Forino M, Malaguti C, Tubaro A, Poletti R, Yasumoto T, Fattorusso E, Rossini GP (2004) Structure-activity relationships of yessotoxins in cultured cells. Chem Res Toxicol 17: 1251–1257

    Article  CAS  PubMed  Google Scholar 

  99. Moore RE, Bartolini G (1981) Structure of palytoxin. J Am Chem Soc 103: 2491–2494

    Article  CAS  Google Scholar 

  100. Uemura D, Ueda K, Hirata Y, Naoki H, Iwashita T (1981) Further studies on palytoxin. 1. Tetrahedron Lett 22: 1909–1912

    Article  CAS  Google Scholar 

  101. Uemura D, Ueda K, Hirata Y, Naoki H, Iwashita T (1981) Further studies on palytoxin. 2. Structure of palytoxin. Tetrahedron Lett 22: 2781–2784

    Article  CAS  Google Scholar 

  102. Katikou P (2008) Palytoxin and analogues: Ecobiology and origin, chemistry, metabolism, and chemical analysis. In: LM Botana (ed.): Seafood and Freshwater Toxins — Pharmacology, Physiology and Detection, CRC Press, Taylor & Francis Group, Boca Raton, FL, 631–663

    Google Scholar 

  103. Kita M, Uemura D (2008) Diverse chemical structures and bioactivities of marine toxins: Palytoxin and symbiodinolide. In: LM Botana (ed.): Seafood and Freshwater Toxins — Pharmacology, Physiology and Detection, CRC Press, Taylor & Francis Group, Boca Raton, FL, 665–674

    Google Scholar 

  104. Kimura S, Hashimoto Y, Yamazato K (1972) Toxicity of the zoanthid Palythoa tuberculosa. Toxicon 10: 611–617

    Article  CAS  PubMed  Google Scholar 

  105. Onuma Y, Satake M, Ukena T, Roux J, Chanteau S, Rasolofonirina N, Ratsimaloto M, Naoki H, Yasumoto T (1999) Identification of putative palytoxin as the cause of clupeotoxism. Toxicon 37: 55–65

    Article  CAS  PubMed  Google Scholar 

  106. Penna A, Vila M, Fraga S, Giacobbe MG, Andreoni F, Riobo P, Vernesi C (2005) Characterization of Ostreopsis and Coolia (Dinophyceae) isolates in the western Mediterranean sea based on morphology, toxicity and internal transcribed spacer 5.8S rDNA sequences. J Phycol 41: 212–225

    Article  CAS  Google Scholar 

  107. Lenoir S, Ten-Hage L, Turquet J, Quod JP, Bernard C, Hennion MC (2004) First evidence of palytoxin analogues from an Ostreopsis mascarenensis (Dinophyceae) benthic bloom in Southwestern Indian Ocean. J Phycol 40: 1042–1051

    Article  CAS  Google Scholar 

  108. Moore RE, Bartolini G, Barchi J, Bothnerby AA, Dadok J, Ford J (1982) Absolute stereochemistry of palytoxin. J Am Chem Soc 104: 3776–3779

    Article  CAS  Google Scholar 

  109. Uemura D, Hirata Y, Iwashita T, Naoki H (1985) Studies on palytoxins. Tetrahedron 41: 1007–1017

    Article  CAS  Google Scholar 

  110. Frolova GM, Kuznetsova TA, Mikhailov VV, Elyakov GB (2000) An enzyme linked immunosorbent assay for detecting palytoxin-producing bacteria. Bioorg Khim 26: 315–320

    CAS  PubMed  Google Scholar 

  111. Ciminiello P, Dell’Aversano C, Fattorusso E, Forino M, Tartaglione L, Grillo C, Melchiorre N (2008) Putative palytoxin and its new analogue, ovatoxin-a, in Ostreopsis ovata collected along the Ligurian coasts during the 2006 toxic outbreak. J Am Soc Mass Spectrom 19: 111–120

    Article  CAS  PubMed  Google Scholar 

  112. Aligizaki K, Katikou P, Nikolaidis G, Panou A (2008) First episode of shellfish contamination by palytoxin-like compounds from Ostreopsis species (Aegean Sea, Greece). Toxicon 51: 418–427

    Article  CAS  PubMed  Google Scholar 

  113. Uemura D, Chou T, Haino T, Nagatsu A, Fukuzawa S, Zheng S, Chen H (1995) Pinnatoxin A: A toxic amphoteric macrocycle from the Okinawan bivalve Pinna muricata. J Am Chem Soc 117: 1155–1156

    Article  CAS  Google Scholar 

  114. Takada N, Umemura N, Suenaga K, Uemura D (2001) Structural determination of pteriatoxins A, B and C, extremely potent toxins from the bivalve Pteria penguin. Tetrahedron Lett 42: 3495–3497

    Article  CAS  Google Scholar 

  115. Lu CK, Lee GH, Huang R, Chou HN (2001) Spiro-prorocentrimine, a novel macrocyclic lactone from a benthic Prorocentrum sp of Taiwan. Tetrahedron Lett 42: 1713–1716

    Article  CAS  Google Scholar 

  116. Seki T, Satake M, MacKenzie L, Kaspar HF, Yasumoto T (1995) Gymnodimine, a new marine toxin of unprecedented structure isolated from New Zealand oysters and the dinoflagellate, Gymnodinium sp. Tetrahedron Lett 36: 7093–7096

    Article  Google Scholar 

  117. Hu TM, Curtis JM, Walter JA, Wright JLC (1996) Characterization of biologically inactive spirolides E and F: Identification of the spirolide pharmacophore. Tetrahedron Lett 37: 7671–7674

    Article  CAS  Google Scholar 

  118. McCauley JA, Nagasawa K, Lander PA, Mischke SG, Semones MA, Kishi Y (1998) Total synthesis of pinnatoxin A. J Am Chem Soc 120: 7647–7648

    Article  CAS  Google Scholar 

  119. Molgo J, Girard E, Benoit E (2007) Cyclic imines: An insight into this emerging group of bioactive marine toxins. In: LM Botana (ed.): Phycotoxins, Chemistry and Biochemistry, Blackwell Publishing, Oxford, 319–335

    Chapter  Google Scholar 

  120. Cembella AD, Krock B (2008) Cyclic imine toxins: Chemistry, biogeography, biosynthesis and pharmacology. In: LM Botana (ed.): Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, Taylor & Francis Ltd, Boca Raton, FL, 561–580

    Google Scholar 

  121. Munday R (2008) Toxicology of cyclic imines: Gymnodimine, spirolides, pinnatoxins, pteriatoxins, prorocentrolide, spiro-prorocentrimine and symbioimines. In: LM Botana (ed.): Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, Taylor & Francis Ltd, Boca Raton, FL, 581–594

    Google Scholar 

  122. Baden DG, Bourdelais AJ, Jacocks H, Michelliza S, Naar J (2005) Natural and derivative brevetoxins: Historical background, multiplicity, and effects. Environ Health Perspect 113: 621–625

    CAS  PubMed  Google Scholar 

  123. Satake M, Shoji M, Oshima Y, Naoki H, Fujita T, Yasumoto T (2002) Gymnocin-A, a cytotoxic polyether from the notorious red tide dinoflagellate, Gymnodinium mikimotoi. Tetrahedron Lett 43: 5829–5832

    Article  CAS  Google Scholar 

  124. Pierce RH, Henry MS, Blum PC, Hamel SL, Kirkpatrick B, Cheng YS, Zhou Y, Irvin CM, Naar J, Weidner A, Fleming LE, Backer LC, Baden DG (2005) Brevetoxin composition in water and marine aerosol along a Florida beach: Assessing potential human exposure to marine biotoxins. Harmful Algae 4: 965–972

    Article  CAS  Google Scholar 

  125. Alam M, Sanduja R, Hossain MB, van der Helm D (1982) Gymnodinium breve toxins. I. Isolation and X-ray structure of O,O-dipropyl (E)-2-(1-methyl-2-oxopropylidene)phosphorohydrazidothioate (E)-oxime from the red tide dinoflagellate Gymnodinium breve. J Am Chem Soc 104: 5232–5234

    Article  CAS  Google Scholar 

  126. Lin YY, Risk M, Ray SM, van Engen D, Clardy J, Golik J, James JC, Nakanishi K (1981) Isolation and structure of brevetoxin B from the “red tide” dinoflagellate Ptychodiscus brevis (Gymnodinium breve). J Am Chem Soc 103: 6773–6775

    Article  CAS  Google Scholar 

  127. Shimizu Y, Chou HN, Bando H, van Duyne G, Clardy JC (1986) Structure of brevetoxin A (GB-1 toxin), the most potent toxin in the Florida red tide organism Gymnodinium breve (Ptychodiscus brevis). J Am Chem Soc 108: 515–516

    Article  Google Scholar 

  128. Plakas SM, Wang ZH, El Said KR, Jester ELE, Granade HR, Flewelling L, Scott P, Dickey RW (2004) Brevetoxin metabolism and elimination in the Eastern oyster (Crassostrea virginica) after controlled exposures to Karenia brevis. Toxicon 44: 677–685

    Article  CAS  PubMed  Google Scholar 

  129. Wang Z, Plakas SM, El Said KR, Jester ELE, Granade HR, Dickey RW (2004) LC/MS analysis of brevetoxin metabolites in the Eastern oyster (Crassostrea virginica). Toxicon 43: 455–465

    Article  CAS  PubMed  Google Scholar 

  130. Abraham A, Plakas SM, Wang ZH, Jester ELE, El Said KR, Granade HR, Henry MS, Blum PC, Pierce RH, Dickey RW (2006) Characterization of polar brevetoxin derivatives isolated from Karenia brevis cultures and natural blooms. Toxicon 48: 104–115

    Article  CAS  PubMed  Google Scholar 

  131. Rein KS, Lynn B, Gawley RE, Baden DG (1994) Brevetoxin B: Chemical modifications, synaptosome binding, toxicity, and an unexpected conformational effect. J Org Chem 59: 2107–2113

    Article  CAS  Google Scholar 

  132. Bourdelais AJ, Campbell S, Jacocks H, Naar J, Wright J, Carsi J, Baden DG (2004) Brevenal is a natural inhibitor of brevetoxin action in sodium channel receptor binding assays. Cell Mol Neurobiol 24: 553–563

    Article  CAS  PubMed  Google Scholar 

  133. Dechraoui MYB, Wacksman JJ, Ramsdell JS (2006) Species selective resistance of cardiac muscle voltage gated sodium channels: Characterization of brevetoxin and ciguatoxin binding sites in rats and fish. Toxicon 48: 702–712

    Article  PubMed  CAS  Google Scholar 

  134. Murata M, Yasumoto T (2000) The structure elucidation and biological activities of high molecular weight algal toxins: Maitotoxin, prymnesins and zooxanthellatoxins. Nat Prod Rep 17: 293–314

    Article  CAS  PubMed  Google Scholar 

  135. Murata M, Legrand AM, Ishibashi Y, Yasumoto T (1989) Structures of ciguatoxin and its congener. J Am Chem Soc 111: 8929–8931

    Article  CAS  Google Scholar 

  136. Murata M, Legrand AM, Ishibashi Y, Fukui M, Yasumoto T (1990) Structures and configurations of ciguatoxin from the moray eel Gymnothorax javanicus and its likely precursor from the dinoflagellate Gambierdiscus toxicus. J Am Chem Soc 112: 4380–4386

    Article  CAS  Google Scholar 

  137. Legrand AM, Fukui M, Cruchet P, Yasumoto T (1992) Progress on chemical knowledge of ciguatoxins. Bull Soc Pathol Exot 85: 467–469

    CAS  PubMed  Google Scholar 

  138. Lewis RJ, Sellin M, Poli MA, Norton RS, MacLeod JK, Sheil MM (1991) Purification and characterization of ciguatoxins from moray eel (Lycodontis javanicus, Muraenidae). Toxicon 29: 1115–1127

    Article  CAS  PubMed  Google Scholar 

  139. Poli MA, Lewis RJ, Dickey RJ, Musser SM, Buckner CA, Carpenter LG (1997) Identification of Caribbean ciguatoxins as the cause of an outbreak of fish poisoning among U.S. soldiers in Haiti. Toxicon 35: 733–741

    Article  CAS  PubMed  Google Scholar 

  140. Satake M, Murata M, Yasumoto T (1993) The structure of CTX3C, a ciguatoxin congener isolated from cultured Gambierdiscus toxicus. Tetrahedron Lett 34: 1975–1978

    Article  CAS  Google Scholar 

  141. Satake M, Morohashi A, Oguri H, Oishi T, Hirama M, Harada N, Yasumoto T (1997) The absolute configuration of ciguatoxin. J Am Chem Soc 119: 11325–11326

    Article  CAS  Google Scholar 

  142. Satake M, Fukui M, Legrand AM, Cruchet P, Yasumoto T (1998) Isolation and structures of new ciguatoxin analogs, 2,3-dihydroxyCTX3C and 51-hydroxyCTX3C, accumulated in tropical reef fish. Tetrahedron Lett 39: 1197–1198

    Article  CAS  Google Scholar 

  143. Dickey RW (2008) Ciguatera toxins: Chemistry, toxicology and detection. In: LM Botana (ed.): Seafood and Freshwater Toxins — Pharmacology, Physiology and Detection, CRC Press, Taylor & Francis Group, Boca Raton, FL, 479–500

    Google Scholar 

  144. Chateau-Degat ML, Chinain M, Cerf N, Gingras S, Hubert B, Dewailly E (2005) Seawater temperature, Gambierdiscus spp. variability and incidence of ciguatera poisoning in French Polynesia. Harmful Algae 4: 1053–1062

    Article  CAS  Google Scholar 

  145. Yasumoto T, Nakajima I, Bagnis R, Adachi R (1977) Finding of a dinoflagellate as a likely culprit of ciguatera. Bull Jap Soc Sci Fish 43: 1021–1026

    Google Scholar 

  146. Adachi R, Fukuyo Y (1979) The thecal structure of a toxic marine dinoflagellate Gambierdiscus toxicus gen. et spec. nov. collected in a ciguatera-endemic area. Bull Jap Soc Sci Fish 45: 67–71

    Google Scholar 

  147. Aasen JAB, Hardstaff W, Aune T, Quilliam M (2006) Discovery of fatty acid ester metabolites of spirolide toxins in mussels from Norway using liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 20: 1531–1537

    Article  CAS  PubMed  Google Scholar 

  148. Ciminiello P, Fattorusso E, Forino M, Poletti R, Viviani R (2000) Structure determination of carboxyhomoyessotoxin, a new yessotoxin analogue isolated from Adriatic mussels. Chem Res Toxicol 13: 770–774

    Article  CAS  PubMed  Google Scholar 

  149. Miles CO, Wilkins AL, Selwood AI, Hawkes AD, Jensen DJ, Cooney JM, Beuzenberg V, MacKenzie AL (2006) Isolation of yessotoxin 32-O-[β-L-arabinofuranosyl-(5′→1″)-β-L-arabinofuranoside] from Protoceratium reticulatum. Toxicon 47: 510–516

    Article  CAS  PubMed  Google Scholar 

  150. Castèle S, Catterall WA (2000) Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82: 883–892

    Article  Google Scholar 

  151. Hartshorne RP, Catterall WA (1984) The sodium channel from rat brain. Purification and subunit composition. J Biol Chem 259: 1667–1675

    CAS  PubMed  Google Scholar 

  152. Hille B (1975) The receptor for tetrodotoxin and saxitoxin: A structural hypothesis. Biophys J 15: 615–619

    Article  CAS  PubMed  Google Scholar 

  153. Hille B (1968) Pharmacological modifications of the sodium channels of frog nerves. J Gen Physiol 51: 199–219

    Article  CAS  PubMed  Google Scholar 

  154. Wang J, Salata JJ, Bennett PB (2003) Saxitoxin is a gating modifier of hERG K+ channels. J Gen Physiol 121: 583–598

    Article  CAS  PubMed  Google Scholar 

  155. Su Z, Sheets M, Hishida H, Li F, Barry WH (2004) Saxitoxin blocks L-type I Ca. J Pharmacol Exp Ther 308: 324–329

    Article  CAS  PubMed  Google Scholar 

  156. Llewellyn LE (2006) Saxitoxin, a toxic marine natural product that targets a multitude of receptors. Nat Prod Rep 23: 200–222

    Article  CAS  PubMed  Google Scholar 

  157. Lombert A, Bidard JN, Lazdunski M (1987) Ciguatoxins and brevetoxins share a common receptor site on the neuronal voltage-dependent Na+ channel. FEBS Lett 219: 355–357

    Article  Google Scholar 

  158. Randall JE (1958) A review of ciguatera, tropical fish poisoning, with a tentative explanation of its cause. Bull Mar Sci Gulf Carib 8: 236–267

    Google Scholar 

  159. Terao K (2000) Ciguatera toxins: Toxinology. In: LM Botana (ed.): Seafood and Freshwater Toxins, Marcel Dekker, New York, 449–472

    Google Scholar 

  160. Gusovsky F, Daly JL (1990) Maitotoxin: A unique pharmacological tool for research on calcium-dependent mechanisms. Biochem Pharmacol 39: 1633–1639

    Article  CAS  PubMed  Google Scholar 

  161. Trevino CL, Escobar L, Vaca L, Morales-Tlalpan V, Ocampo AY, Darszon A (2008) Maitotoxin: Aunique pharmacological tool for elucidating Ca2+-dependent mechanisms. In: LM Botana (ed.): Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, Taylor & Francis Ltd, Boca Raton, FL, 503–516

    Google Scholar 

  162. Morales-Tlalpan V, Vaca L (2002) Modulation of the maitotoxin response by intracellular and extracellular cations. Toxicon 40: 493–500

    Article  CAS  PubMed  Google Scholar 

  163. Dietl P, Völkl H (1994) Maitotoxin activates a nonselective cation channel and stimulates Ca2+ entry in MDCK renal epithelial cells. Mol Pharmacol 45: 300–305

    CAS  PubMed  Google Scholar 

  164. Estacion M, Nguyen HB, Gargus JJ (1996) Calcium is permeable through a maitotoxin-activated nonselective cation channel in mouse L cells. Am J Physiol 270: C1145–C1152

    CAS  PubMed  Google Scholar 

  165. Leech CA, Habner JF (1997) Insulinotropic glucagon-like peptide-1-mediated activation of non-selective cation currents in insulinoma cells is mimicked by maitotoxin. J Biol Chem 272: 17987–17993

    Article  CAS  PubMed  Google Scholar 

  166. Ohizumi Y, Yasumoto T (1983) Contraction and increase in tissue calcium content induced by maitotoxin, the most potent known marine toxin, in intestinal smooth muscle. Br J Pharmacol 79: 3–5

    CAS  PubMed  Google Scholar 

  167. Takahashi M, Tatsumi M, Ohizumi Y, Yasumoto T (1983) Ca2+ channel activating function of maitotoxin, the most potent marine toxin known, in clonal rat pheochromocytoma cells. J Biol Chem 258: 10944–10949

    CAS  PubMed  Google Scholar 

  168. Schettini G, Koike K, Login IS, Judd AM, Cronin MJ, Yasumoto T, MacLeod RM (1984) Maitotoxin stimulates hormonal release and calcium influx in rat anterior pituitary cells in vitro. Am J Physiol 247: E520–E525

    CAS  PubMed  Google Scholar 

  169. Holz GG, Leech CA, Habener JF (2000) Insulinotropic toxins as molecular probes for analysis of glucagon-like peptide-1 receptor-mediated signal transduction in pancreatic β-cells. Biochimie 82: 915–926

    Article  CAS  PubMed  Google Scholar 

  170. Gusovsky F, Daly JW, Yasumoto T, Rojas E (1988) Differential effects of maitotoxin on ATP secretion and on phosphoinositide breakdown in rat pheochromocytoma cells. FEBS Lett 233: 139–142

    Article  CAS  PubMed  Google Scholar 

  171. Choi OH, Gusovsky F, Yasumoto T, Daly JW (1990) Maitotoxin: Effects on calcium channels, phosphoinositide breakdown, and arachidonate release in pheochromocytoma PC12 cells. Mol Pharmacol 37: 222–230

    CAS  PubMed  Google Scholar 

  172. Gusovsky F, Yasumoto T, Daly JW (1989) Calcium-dependent effects of maitotoxin on phosphoinositide breakdown and on cyclic AMP accumulation in PC12 and NCB-20 cells. Mol Pharmacol 36: 44–53

    CAS  PubMed  Google Scholar 

  173. Malaguti C, Yasumoto T, Rossini GP (1999) Transient Ca2+-dependent activation of ERK1 and ERK2 in cytotoxic responses induced by maitotoxin in breast cancer cells. FEBS Lett 458: 137–140

    Article  CAS  PubMed  Google Scholar 

  174. Kobayashi M, Kondo S, Yasumoto T, Ohizumi Y (1986) Cardiotoxic effects of maitotoxin, a principal toxin of seafood poisoning, on guinea pig and rat cardiac muscle. J Pharmacol Exp Ther 238: 1077–1083

    CAS  PubMed  Google Scholar 

  175. Terao K, Ito E, Sakamaki Y, Igarashi K, Yokoyama A, Yasumoto T (1988) Histopathological studies of experimental marine toxin poisoning. II. The acute effects of maitotoxin on the stomach, heart, and lymphoid tissues in mice and rats. Toxicon 26: 395–402

    Article  CAS  PubMed  Google Scholar 

  176. Ghiaroni V, Sasaki M, Fuwa H, Rossini GP, Scalera G, Yasumoto T, Pietra P, Bigiani A (2005) Inhibition of voltage-gated potassium currents by gambiero in mouse taste cells. Toxicol Sci 85: 657–665

    Article  CAS  PubMed  Google Scholar 

  177. Cuypers E, Abdel-Mottaleb Y, Kopljar I, Rainier JD, Raes AL, Snyders DJ, Tytgat J (2008) Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels. Toxicon 51: 974–983

    Article  CAS  PubMed  Google Scholar 

  178. Louzao MC, Cagide E, Vieytes MR, Sasaki M, Fuwa H, Yasumoto T, Botana LM (2006) The sodium channel of human excitable cells is a target for gambierol. Cell Physiol Biochem 17: 257–268

    Article  CAS  PubMed  Google Scholar 

  179. Sala GL, Ronzitti G, Sasaki M, Fuwa H, Yasumoto T, Bigiani A, Rossini GP (2009) Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture. Chem Res Toxicol 22: 1077–1085

    Article  CAS  PubMed  Google Scholar 

  180. Habermann E, Chhatwal GS (1982) Ouabain inhibits the increase due to palytoxin of cationic permeability of erythrocytes. Naunyn-Schmeideberg’s Arch Pharmacol 319: 101–107

    Article  CAS  Google Scholar 

  181. Muramatsu I, Nishio M, Kigoshi S, Uemura D (1988) Single ionic channels induced by palytoxin in guinea-pig ventricular myocytes. Br J Pharmacol 93: 811–816

    CAS  PubMed  Google Scholar 

  182. Ikeda M, Mitani K, Ito K (1988) Palytoxin induces a nonselective cation channel in single ventricular cells of rat. Naunyn-Schmeideberg’s Arch Pharmacol 337: 591–593

    CAS  Google Scholar 

  183. Artigas P, Gadsby DC (2003) Na+/K+-pump ligands modulate gating of palytoxin-induced ion channels. Proc Natl Acad Sci USA 100: 501–505

    Article  CAS  PubMed  Google Scholar 

  184. Artigas P, Gadsby DC (2004) Large diameter of palytoxin-induced the Na/K pump channels and modulation of palytoxin interaction by Na/K pump ligands. J Gen Physiol 123: 357–376

    Article  CAS  PubMed  Google Scholar 

  185. Artigas P, Gadsby DC (2006) Ouabain affinity determining residues lie close to the Na/K pump ion pathway. Proc Natl Acad Sci USA 103: 12613–12618

    Article  CAS  PubMed  Google Scholar 

  186. Reyes N, Gadsby DC (2006) Ion permeation through the Na+/K+-ATPase. Nature 443: 470–474

    Article  CAS  PubMed  Google Scholar 

  187. Takeuchi A, Reyes N, Artigas P, Gadsby DC (2008) The ion pathway through the opened Na+, K+-ATPase pump. Nature 456: 413–416

    Article  CAS  PubMed  Google Scholar 

  188. Habermann E, Ahnert-Hilger G, Chhatwal GS, Beress L (1981) Delayed haemolytic action of palytoxin. General characteristics. Biochim Biophys Acta 649: 481–486

    Article  CAS  PubMed  Google Scholar 

  189. Redondo J, Fiedler B, Scheiner-Bobis G (1996) Palytoxin-induced Na+ influx into yeast cells expressing the mammalian sodium pump is due to the formation of a channel within the enzyme. Mol Pharmacol 49: 49–57

    CAS  PubMed  Google Scholar 

  190. Hirsh JK, Wu CH (1997) Palytoxin-induced single-channel currents from the sodium pump synthesized by in vitro expression. Toxicon 35: 169–176

    Article  CAS  PubMed  Google Scholar 

  191. Frelin C, van Renterghem C (1995) Palytoxin. Recent electrophysiological and pharmacological evidence for several mechanisms of action. Gen Pharmacol 26: 33–37

    CAS  PubMed  Google Scholar 

  192. Sauviat MP (1989) Effect of palytoxin on the calcium current and the mechanical activity of frog heart muscle. Br J Pharmacol 98: 773–780

    CAS  PubMed  Google Scholar 

  193. Kockskämper J, Ahmmed GU, Zima AV, Sheehan KA, Glitsch HG, Blater LA (2004) Palytoxin disrupts cardiac excitation-contraction coupling through interactions with P-type ion pumps. Am J Cell Physiol 287: C527–C538

    Article  Google Scholar 

  194. Vale C, Alfonso A, Suñol C, Vieytes MR, Botana LM (2006) Modulation of calcium entry and glutamate release in cultured cerebellar granule cells by palytoxin. J Neurosci Res 83: 1393–1406

    Article  CAS  PubMed  Google Scholar 

  195. Ito K, Karaki H, Urakawa N (1977) The mode of contractile action of palytoxin on vascular smooth muscle. Eur J Pharmacol 46: 9–14

    Article  CAS  PubMed  Google Scholar 

  196. Frelin C, Vigne P, Breittmayer JP (1990) Palytoxin acidifies chick cardiac cells and activates the Na+/H+ antiporter. FEBS Lett 264: 63–66

    Article  CAS  PubMed  Google Scholar 

  197. Yoshizumi M, Houchi H, Ishimura Y, Masuda Y, Morita K, Oka M (1991) Mechanism of palytoxin-induced Na+ influx into cultured bovine adrenal chromaffin cells: Possible involvement of Na+/H+ exchange system. Neurosci Lett 130: 103–106

    Article  CAS  PubMed  Google Scholar 

  198. Monroe JJ, Tashjan AH Jr (1996) Palytoxin modulates cytosolic pH in human osteoblast-like Saos-2 cells via an interaction with Na+−K+-ATPase. Am J Physiol 270: C1277–C1283

    CAS  PubMed  Google Scholar 

  199. Levine L, Fujiki H (1985) Stimulation of arachidonic acid metabolism by different types of tumor promoters. Carcinogenesis 6: 1631–1634

    Article  CAS  PubMed  Google Scholar 

  200. Lazzaro M, Tshjian AH Jr, Fujiki H, Levine L (1987) Palytoxin: An extraordinary potent stimulator of prostaglandin production and bone resorption in cultured mouse clavariae. Endocrinology 120: 1338–1345

    Article  CAS  PubMed  Google Scholar 

  201. Miura D, Kobayashi M, Kakiuchi S, Kasahara Y, Kondo S (2006) Enhancement of transformed foci and induction of prostaglandins in Balb/c 3T3 cells by palytoxin: In vitro model reproduces carcinogenic responses in animal models regarding the inhibitory effect of indomethacin and reversal of indomethacin’s effect by exogenous prostaglandins. Toxicol Sci 89: 154–163

    Article  CAS  PubMed  Google Scholar 

  202. Nagase H, Karaki H (1987) Palytoxin-induced contraction and release of prostaglandins and norepinepfrine in the aorta. J Pharmacol Exp Ther 242: 1120–1125

    CAS  PubMed  Google Scholar 

  203. Fujiki H, Suganuma M, Nakayasu M, Hakii H, Horiuchi T, Takayama S, Sugimura T (1986) Palytoxin is a non-12-O-tetradecanoylphorbol-13-acetate type tumor promoter in two-stage mouse skin carcinogenesis. Carcinogenesis 7: 707–710

    Article  CAS  PubMed  Google Scholar 

  204. Katz M, Amit I, Yarden Y (2007) Regulation of MAPKs by growth factors and receptor tyrosine kinases. Biochim Biophys Acta 1773: 1161–1176

    Article  CAS  PubMed  Google Scholar 

  205. Wattenberg EV (2007) Palytoxin: Exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis. Am J Cell Physiol 292: C24–C32

    Article  CAS  Google Scholar 

  206. Bellocci M, Ronzitti G, Milandri A, Melchiorre N, Grillo C, Poletti R, Yasumoto T, Rossini GP (2008) A cytolytic assay for the measurement of palytoxin based on a cultured monolayer cell line. Anal Biochem 374: 48–55

    Article  CAS  PubMed  Google Scholar 

  207. Meldrum BS (2000) Glutamate as a neurotransmitter in the brain: Review of physiology and pathology. J Nutr 130: 1007S–1015S

    CAS  PubMed  Google Scholar 

  208. Pulido OM (2008) Domoic acid toxicologic pathology: A review. Mar Drugs 6: 180–219

    CAS  PubMed  Google Scholar 

  209. Doucette DA, Tasker RA (2008) Domoic acid: Detection methods, pharmacology, and toxicology. In: LM Botana (ed.): Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, Taylor & Francis Ltd, Boca Raton, FL, 397–429

    Google Scholar 

  210. Ozawa S, Kamiya H, Tsuzuki K (1998) Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 54: 581–618

    Article  CAS  PubMed  Google Scholar 

  211. Lerma J, Paternain AV, Rodríguez-Moreno A, López-García J (2001) Molecular Physiology of kainate receptors. Physiol Rev 81: 971–998

    CAS  PubMed  Google Scholar 

  212. Xi D, Ramsdell JS (1996) Glutamate receptors and calcium entry mechanisms for domoic acid in hippocampal neurons. Neuro Report 26: 1115–1120

    Google Scholar 

  213. Berman FW, LePage KT, Murray TF (2002) Domoic acid neurotoxicity in cultured cerebellar granule neurons is controlled by the NMDA receptor Ca2+ influx pathway. Brain Res 924: 20–29

    Article  CAS  PubMed  Google Scholar 

  214. Brown JA, Njjar MS (1995) The release of glutamate and aspartate from rat brain synaptosomes in response to domoic acid (amnesic shellfish toxin) and kainic acid. Mol Cell Biochem 151: 49–54

    Article  CAS  PubMed  Google Scholar 

  215. Malva JO, Carvalho AP, Carvalho CM (1996) Domoic acid induces the release of glutamate in the rat hippocampal CA3 sub-region. Neuro Report 7: 1330–1334

    CAS  Google Scholar 

  216. Berman FW, Murray TF (1997) Domoic acid neurotoxicity in cultured crebellar granule neurons is mediated predominantly by NMDA receptors that are activated as a consequence of excitatory amino acid release. J Neurochem 69: 693–703

    Article  CAS  PubMed  Google Scholar 

  217. Novelli A, Kispert J, Fernández-Sánchez MT, Torreblanca A, Zitko V (1992) Domoic acid-containing toxic mussels produce neurotoxicity in neuronal cultures through a synergism between excitatory amino acids. Brain Res 577: 41–48

    Article  CAS  PubMed  Google Scholar 

  218. Berman FW, Murray TF (1996) Characterization of glutamate toxicity in cultured rat cerebellar granule neurons at reduced temperature. J Biochem Toxicol 11: 111–119

    Article  CAS  PubMed  Google Scholar 

  219. Bowie D, Lange GD (2002) Functional stoichiometry of glutamate receptor desensitization. J Neurosci 22: 3392–3403

    CAS  PubMed  Google Scholar 

  220. Teitelbaum JS, Zatorre RJ, Carpenter S, Gendron D, Evans AC, Gjedde A, Cashman NR (1990) Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. N Engl J Med 322: 1781–1787

    Article  CAS  PubMed  Google Scholar 

  221. Cendes F, Andermann F, Carpenter S, Zatorre RJ, Cashman NR (1995) Temporal lobe epilepsy caused by domoic acid intoxication: Evidence for glutamate receptor-mediated excitotoxicity in humans. Ann Neurol 37: 123–126

    Article  CAS  PubMed  Google Scholar 

  222. Tasker RA, Strain SM, Drejer J (1996) Selective reduction in domoic acid toxicity in vivo by a novel non-N-methyl-d-aspartate receptor antagonist. Can J Physiol Pharmacol 74: 1047–1054

    Article  CAS  PubMed  Google Scholar 

  223. Jakobsen B, Tasker A, Zimmer J (2002) Domoic acid neurotoxicity in hippocampal slice cultures. Amino Acids 23: 37–44

    Article  CAS  PubMed  Google Scholar 

  224. Giordano G, White CC, Mohar I, Kavanagh TJ, Costa LG (2007) Glutathione levels modulate domoic acid induced apoptosis in mouse cerebellar granule cells. Toxicol Sci 100: 433–444

    Article  CAS  PubMed  Google Scholar 

  225. Gill S, Murphy M, Clausen J, Richard D, Quilliam M, MacKinnon S, LaBlanc P, Mueller R, Pulido O (2003) Neural injury biomarkers of novel shellfish toxins, spirolides: A pilot study using immunochemical and transcriptional analysis. Neuro Toxicology 24: 593–604

    CAS  Google Scholar 

  226. Bialojan C, Takai A (1988) Inhibitory effect of a marine sponge toxin, okadaic acid, on protein phosphatases. Biochem J 256: 283–290

    CAS  PubMed  Google Scholar 

  227. Takai A, Mieskes G (1991) Inhibitory effect of okadaic acid on the p-nitrophenyl phosphate phosphatase activity of protein phosphatases. Biochem J 275: 233–239

    CAS  PubMed  Google Scholar 

  228. Krebs EG (1985) The phosphorylation of proteins: A major mechanism for biological regulation. Biochem Soc Trans 13: 813–820

    CAS  PubMed  Google Scholar 

  229. Roach PJ (1991) Multisite and hierarchal protein phosphorylation. J Biol Chem 266: 14139–14142

    CAS  PubMed  Google Scholar 

  230. Kholodenko BN (2006) Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol 7: 165–176

    Article  CAS  PubMed  Google Scholar 

  231. Hunter T (1995) Protein kinases and phosphatases: The yin and yang of protein phosphorylation and signaling. Cell 80: 225–236

    Article  CAS  PubMed  Google Scholar 

  232. Tolstykh T, Lee J, Vafai S, Stock JB (2000) Carboxyl methylation regulates phosphoprotein phosphatase 2A by controlling the association of regulatory B subunits. EMBO J 19: 5682–5691

    Article  CAS  PubMed  Google Scholar 

  233. Haystead TA, Sim ATR, Carling D, Honnor RC, Tsukitani Y, Cohen P, Hardie DG (1989) Effects of the tumor promoter okadaic acid on intracellular protein phosphorylation and metabolism. Nature 337: 78–81

    Article  CAS  PubMed  Google Scholar 

  234. Suganuma M, Fujiki H, Suguri H, Yoshizawa S, Hirota M, Nakayasu M, Ojika M, Wakamatsu K, Yamada K, Sugimura T (1988) Okadaic acid: An additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proc Natl Acad Sci USA 85: 1768–1771

    Article  CAS  PubMed  Google Scholar 

  235. Suganuma M, Tatematsu M, Yatsunami J, Yoshizawa S, Okabe S, Uemura D, Fujiki H (1992) An alternative theory of tissue specificity by tumor promotion of okadaic acid in glandular stomach of SD rats. Carcinogenesis 13: 1841–1845

    Article  CAS  PubMed  Google Scholar 

  236. Berenblum I, Haran-Ghera N (1955) The significance of the sequence of initiating and promoting actions in the process of skin carcinogenesis in mouse. Br J Cancer 3: 268–271

    Google Scholar 

  237. Rossini GP (2000) Neoplastic activity of DSP toxins: The effects of okadaic acid and related compounds on cell proliferation: Tumor promotion or induction of apoptosis? In: LM Botana, (ed.). Seafood and Freshwater Toxins, Marcel Dekker, New York, 257–288

    Google Scholar 

  238. Tripuraneni J, Koutsoris A, Pestic L, De Lanerolle P, Hect G (1997) The toxin of diarrhetic shell-fish poisoning, okadaic acid, increases intestinal epithelial paracellular permeability. Gastroenterology 112: 100–108

    Article  CAS  PubMed  Google Scholar 

  239. Nollet F, Kools P, van Roy F (2000) Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J Mol Biol 299: 551–572

    Article  CAS  PubMed  Google Scholar 

  240. Malaguti C, Rossini GP (2002) Recovery of cellular E-cadherin precedes replenishment of estrogen receptor and estrogen-dependent proliferation of breast cancer cells rescued from a death stimulus. J Cell Physiol 192: 171–181

    Article  CAS  PubMed  Google Scholar 

  241. Hosokawa M, Tsukada H, Saitou T, Kodama M, Onomura M, Nakamura H, Fukuda K, Seino Y (1998) Effects of okadaic acid on rat colon. Dig Dis Sci 43: 2526–2535

    Article  CAS  PubMed  Google Scholar 

  242. EFSA (2008) Marine biotoxins in shellfish — Azaspiracid group, Scientific Opinion of the Panel on Contaminants in the Food chain EFSA J 723: 1–52

    Google Scholar 

  243. Tubaro A, Giangaspero A, Ardizzone M, Soranzo MR, Vita F, Yasumoto T, Maucher JM, Ramsdell JS, Sosa S (2008) Ultrastructural damage to heart tissue from repeated oral exposure to yessotoxin resolves in 3 months. Toxicon 51: 1225–1235

    Article  CAS  PubMed  Google Scholar 

  244. Rossini GP, Ronzitti G, Callegari F (2006) The modes of action of yessotoxin and the toxic responses of cellular systems. In: F Goudey-Perrière, E Benoit, M Goyffon, P Marchot (eds): Toxines et Cancer, Lavoisier, Paris, 67–76

    Google Scholar 

  245. Paz B, Daranas AH, Norte M, Riobó P, Franco JM, Fernández JJ (2008) Yessotoxins, a group of marine polyether toxins: An overview. Mar Drugs 6: 73–102

    CAS  PubMed  Google Scholar 

  246. Alfonso A, Alfonso C (2008) Pharmacology and mechanism of action: Biological detection. In: LM Botana (ed.): Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, Taylor & Francis Ltd, Boca Raton, FL, 315–327

    Google Scholar 

  247. Twiner MJ, Hess P, Bottein Dechraoui MY, McMahon T, Samons MS, Satake M, Yasumoto T, Ramsdell JS, Doucette GJ (2005) Cytotoxic and cytoskeletal effects of azaspiracid-1 on mammalian cell lines. Toxicon 45: 891–900

    CAS  PubMed  Google Scholar 

  248. Vilariño N, Nicolaou KC, Frederick MO, Cagide E, Ares IR, Louzao MC, Vieytes MR, Botana LM (2006) Cell growth inhibition and actin cytoskeleton disorganization induced by azaspiracid-1 structure-activity studies. Chem Res Toxicol 19: 1459–1466

    Article  PubMed  CAS  Google Scholar 

  249. Ronzitti G, Hess P, Rehmann N, Rossini GP (2007) Azaspiracid-1 alters the E-cadherin pool in epithelial cells. Toxicol Sci 95: 427–435

    Article  CAS  PubMed  Google Scholar 

  250. Vale C, Nicolaou KC, Frederick MO, Gómez-Limia B, Alfonso A, Vieytes MR, Botana LM (2007) Effects of azaspiracid-1, a potent cytotoxic agent, on primary neuronal cultures. A structure-activity relationship study. J Med Chem 50: 356–363

    Article  CAS  PubMed  Google Scholar 

  251. Vale C, Gómez-Limia B, Nicolaou KC, Frederick MO, Vieytes MR, Botana LM (2007) The c-Jun-N-terminal kinase is involved in the neurotoxic effect of azaspiracid-1. Cell Physiol Biochem 20: 957–966

    Article  CAS  PubMed  Google Scholar 

  252. Twiner MJ, Ryan JC, Morey JS, van Dolah FM, Hess P, McMahon T, Doucette GJ (2008) Transcriptional profiling and inhibition of cholesterol biosynthesis in human T lymphocyte cells by the marine toxin azaspiracid. Genomics 91: 289–300

    Article  CAS  PubMed  Google Scholar 

  253. Leira F, Alvarez C, Vieites JM, Vieytes MR, Botana LM (2002) Characterization of distinct apoptotic changes induced by okadaic acid and yessotoxin in the BE(2)-M17 neuroblastoma cell line. Toxicol in Vitro 16: 23–31

    Article  CAS  PubMed  Google Scholar 

  254. Malaguti C, Ciminiello P, Fattorusso E, Rossini GP (2002) Caspase activation and death induced by yessotoxin in HeLa cells. Toxicol in Vitro 16: 357–363

    Article  CAS  PubMed  Google Scholar 

  255. Pérez-Gomez A, Ferrero-Gutierrez A, Novelli A, Franco JM, Paz B, Fernández-Sánchez MT (2006) Potent neurotoxic action of the shellfish biotoxin yessotoxin on cultured crebellar neurons. Toxicol Sci 90: 168–177

    Article  PubMed  CAS  Google Scholar 

  256. Malagoli D, Marchesini E, Ottaviani E (2006) Lysosomal as target of yessotoxin in invertebrate and vertebrate cells. Toxicol Lett 167: 75–83

    Article  CAS  PubMed  Google Scholar 

  257. Dell’Ovo V, Bandi E, Coslovich T, Florio C, Sciancalepore M, Decorti G, Sosa S, Lorenzon P, Yasumoto T, Tubaro A (2008) In vitro effects of yessotoxin on a primary culture of rat cardiomyocytes. Toxicol Sci 106: 392–399

    Article  PubMed  CAS  Google Scholar 

  258. Pierotti S, Malaguti C, Milandri A, Poletti R, Rossini GP (2003) Functional assay to measure yessotoxins in contaminated mussel samples. Anal Biochem 312: 208–216

    Article  CAS  PubMed  Google Scholar 

  259. Ronzitti G, Callegari F, Malaguti C, Rossini GP (2004) Selective disruption of the E-cadherincatenin system by an algal toxin. Br J Cancer 90: 1100–1107

    Article  CAS  PubMed  Google Scholar 

  260. Callegari F, Rossini GP (2008) Yessotoxin inhibits the complete degradation of E-cadherin. Toxicology 244: 133–144

    Article  CAS  PubMed  Google Scholar 

  261. Callegari F, Sosa S, Ferrari S, Soranzo MR, Pierotti S, Yasumoto T, Tubaro A, Rossini GP (2006) Oral administration of yessotoxin stabilizes E-cadherin in mouse colon. Toxicology 227: 145–155

    Article  CAS  PubMed  Google Scholar 

  262. Callegari F, Ronzitti G, Ferrari S, Rossini GP (2004) Yessotoxins alter the molecular structures of cell-cell adhesion in cultured cells. In: K Henshilwood, B Deegan, T McMahon, C Cusack, S Keaveney, J Silke, M O’Cinneide, D Lyions, P Hess (eds): Molluscan Shellfish Safety, Proceedings of the 5th International Conference on Molluscan Shellfish Safety; Galway, 407–413

    Google Scholar 

  263. Kellman R, Schaffner CAM, Grønset TA, Satake M, Ziegler M, Fladmark KE (2009) Proteomic response of human neuroblastoma cells to azaspiracid-1. J Proteomics 72: 695–707

    Article  CAS  Google Scholar 

  264. Young C, Truman P, Boucher M, Keyzers RA, Northcote P, Jordan TW (2009) The algal metabolite yessotoxin affects heterogeneous nuclear ribonucleoproteins in HepG2 cells. Proteomics 9: 2529–2542

    Article  CAS  PubMed  Google Scholar 

  265. Munday R (2008) Toxicology of the pectenotoxins. In: LM Botana (ed.): Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, Taylor & Francis Ltd, Boca Raton, FL, 371–380

    Google Scholar 

  266. Terao K, Ito E, Yanagi T, Yasumoto T (1986) Histopathological studies on experimental marine toxin poisoning. 1. Ultrastructural changes in the small intestine and liver of suckling mice induced by dinophysistoxin-1 and pectenotoxin-1. Toxicon 24: 1141–1151

    Article  CAS  PubMed  Google Scholar 

  267. Zhou ZH, Komivama M, Terao K, Shimada Y (1994) Effects of pectenotoxin-1 on liver cells in vitro. Nat Toxins 2: 132–135

    Article  CAS  PubMed  Google Scholar 

  268. Spector I, Braet F, Shochet NR, Bubb MR (1999) New anti-actin drugs in the study of the organization and function of the actin cytoskeleton. Microsc Res Tech 47: 18–37

    Article  CAS  PubMed  Google Scholar 

  269. Hori M, Matsuura Y, Yoshimoto R, Ozaki H, Yasumoto T, Karaki H (1999) Actin depolymerizing action by marine toxin, pectenotoxin-2. Nippon Yakurigaku Zasshi 114: 225P–229P

    PubMed  Google Scholar 

  270. Leira F, Cabado AG, Vieytes MR, Roman Y, Alfonso A, Botana LM, Yasumoto T, Malaguti C, Rossini GP (2002) The marine toxin pectenotoxin-6 induces in vitro depolymerization of F-actin in neuroblastoma cells. Biochem Pharmacol 63: 1979–1988

    Article  CAS  PubMed  Google Scholar 

  271. Ares IR, Louzao MC, Vieytes MR, Yasumoto T, Botana LM (2005) Actin cytoskeleton of rabbit intestinal cells is a target for potent marine phycotoxins. J Exp Biol 208: 4345–4354

    Article  CAS  PubMed  Google Scholar 

  272. Ares IR, Louzao MC, Espiña B, Vieytes MR, Miles CO, Yasumoto T, Botana LM (2007) Lactone ring of pectenotoxins: A key factor for their activity on cytoskeletal dynamics. Cell Phys Biochem 19: 283–292

    Article  CAS  Google Scholar 

  273. Allingham JS, Miles CO, Rayment I (2007) A structural basis for regulation of actin polymerization by pectenotoxins. J Mol Biol 371: 959–970

    Article  CAS  PubMed  Google Scholar 

  274. Jung JH, Sim CJ, Lee CO (1995) Cytotoxic compounds from a two-sponge association. J Nat Prod 58: 1722–1726

    Article  CAS  PubMed  Google Scholar 

  275. Fladmark KE, Serres HM, Larsen NL, Yasumoto T, Aune T, Døskeland SO (1998) Sensitive detection of apoptogenic toxins in suspension cultures of rat and salmon hepatocytes. Toxicon 36: 1101–1114

    Article  CAS  PubMed  Google Scholar 

  276. Chae HD, Choi TS, Kim BM, Jung YJ, Shin DY (2005) Oocyte-based screening of cytokinesis inhibitors and identification of pectenotoxin-2 that induces Bim/Bax-mediated apoptosis in p53-deficient tumors. Oncogene 24: 4813–4819

    Article  CAS  PubMed  Google Scholar 

  277. Shin DY, Kim GY, Kim ND, Jung JH, Kim SK, Kang HS, Choi YH (2008) Induction of apoptosis by pectenotoxin-2 is mediated with the induction of DR4/DR5, Egr-1 and NAG-1, activation of caspases and modulation of the Bcl-2 family in p53-deficient Hep3B hepatocellular carcinoma cells. Oncol Rep 19: 517–526

    CAS  PubMed  Google Scholar 

  278. Kim MO, Moon DO, Kang SH, Heo MS, Choi YH, Jung JH, Lee JD, Kim GY (2008) Pectenotoxin-2 represses telomerase activity in human leukemia cells through suppression of hTERT gene expression and Akt-dependent hTERT phosphorylation. FEBS Lett 582: 3263–3269

    Article  CAS  PubMed  Google Scholar 

  279. Kim MO, Moon DO, Heo MS, Lee JD, Jung JH, Kim SK, Choi YH, Kim GY (2008) Pectenotoxin-2 abolishes constitutively activated NF-κB, leading to suppression of NF-κB related gene products and potentiation of apoptosis. Cancer Lett 271: 25–33

    Article  CAS  PubMed  Google Scholar 

  280. Moon DO, Kim MO, Kang SH, Lee KJ, Heo MS, Choi KS, Choi YH, Kim GY (2008) Induction of G(2)/M arrest, endoreduplication, and apoptosis by actin depolymerization agent pectenotoxin-2 in human leukemia cells, involving activation of ERK and JNK. Biochem Pharmacol 76: 312–321

    Article  CAS  PubMed  Google Scholar 

  281. Chae HD, Kim BM, Yun UJ, Shin DY (2008) Deregulation of Cdk2 causes Bim-mediated apoptosis in p53-deficient tumors following actin damage. Oncogene 27: 4115–4121

    Article  CAS  PubMed  Google Scholar 

  282. Canete E, Diogene J (2008) Comparative study of the use of neuroblastoma cells (Neuro-2a) and neuroblastomaxglioma hybrid cells (NG108-15) for the toxic effect quantification of marine toxins. Toxicon 52: 541–550

    Article  CAS  PubMed  Google Scholar 

  283. FAO (2004) Marine Biotoxins. FAO Food and Nutrition Paper 80. Food and Agriculture Organization, Rome

    Google Scholar 

  284. Gessner BD, McLaughlin JB (2008) Epidemiologic impact of toxic episodes: Neurotoxic toxins. In: LM Botana (ed.): Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, Taylor & Francis Ltd, Boca Raton, FL, 77–103

    Google Scholar 

  285. Hwang KF, Noguchi T (2007) Tetrodotoxin poisoning. Adv Food Nutr Res 52: 141–236

    Article  CAS  PubMed  Google Scholar 

  286. Gessner BD, Bell P, Doucette GJ, Moczydlowski E, Poli MA, van Dolah F, Hall S (1997) Hypertension and identification of toxin in human urine and serum following a cluster of mussel-associated paralytic shellfish poisoning outbreaks. Toxicon 35: 711–722

    Article  CAS  PubMed  Google Scholar 

  287. Ishida H, Muramatsu M, Kosuge T, Tsuji K (1996) Study on neurotoxic shellfish poisoning involving New Zealand shellfish Crassostrea gigas. In: T Yasumoto, Y Oshima, Y Fukuyo (eds): Harmful and Toxic Algal Blooms, Intergovernmental Oceanographic Commission of UNESCO, 491–494

    Google Scholar 

  288. Baden DG, Mende TJ, Bikhazi G, Leung I (1982) Bronchoconstriction caused by Florida red tide toxins. Toxicon 20: 929–932

    Article  CAS  PubMed  Google Scholar 

  289. Pierce R (1986) Red Tide (Ptychodiscus brevis) toxin aerosols: A review. Toxicon 24: 955–965

    Article  CAS  PubMed  Google Scholar 

  290. Fleming LE, Backer LC, Baden DG (2005) Overview of aerosolized Florida red tide toxins: Exposures and effects. Environ Health Persp 113: 618–620

    Article  CAS  Google Scholar 

  291. Baden DG (1983) Marine foodborne dinoflagellate toxins. Int Rev Cytol 82: 99–150

    Article  CAS  PubMed  Google Scholar 

  292. Mattei C, Molgó J, Legrand AM, Benoit E (1999) Ciguatoxins and brevetoxins: Dissection of their neurobiological actions. J Soc Biol 193: 329–344

    CAS  PubMed  Google Scholar 

  293. Perl TM, Bedard L, Kosatsky T, Hockin JC, Todd EC, Remis RS (1990) An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. N Engl J Med 322: 1775–1780

    Article  CAS  PubMed  Google Scholar 

  294. Tasker RA, Connel BJ, Strain SM (1991) Pharmacology of systemically administered domoic acid in mice. Can J Physiol Pharmacol 69: 378–382

    CAS  PubMed  Google Scholar 

  295. Jarrad LE, Meldrum BS (1993) Selective excitotoxic pathology in the rat hippocampus. Neuropathol Appl Neurobiol 19: 381–389

    Article  Google Scholar 

  296. Larm JA, Beart PM, Cheung NS (1997) Neurotoxic domoic acid produces cytotoxicity via kainate-and AMPA-sensitive receptors in cultured cortical neurones. Neurochem Int 31: 677–682

    Article  CAS  PubMed  Google Scholar 

  297. Xi D, Peng YG, Ramsdell JS (1997) Domoic acid is a potent neurotoxin to neonatal rats. Nat Toxins 5: 74–79

    CAS  PubMed  Google Scholar 

  298. Cordier S, Monfort C, Miossec L, Richardson S, Belin C (2000) Ecological analysis of digestive cancer mortality related to contamination by diarrhetic shellfish poisoning toxins along the coasts of France. Environ Res 84: 145–150

    Article  CAS  PubMed  Google Scholar 

  299. Fleming LE, Baden DG, Bean JA, Weisman RS, Blythe DG (1998) Seafood toxin diseases: Issues in epidemiology and community outreach. In: B Reguera, J Blanco, ML Fernandez, T Wyatt (eds). Harmful Algae, Xunta de Galicia and Intergovernmental Oceanographic Commission of UNESCO, Paris, 245–248

    Google Scholar 

  300. Bagnis R, Kuberski T, Laugier S (1979) Clinical observations on 3009 cases of ciguatera (fish poisoning) in the South Pacific. Am J Trop Med Hyg 28: 1067–1073

    CAS  PubMed  Google Scholar 

  301. Terao K, Ito E, Kakinuma Y, Igarashi K, Kobayashi M, Ohizumi Y, Yasumoto T (1989) Histopathological studies on experimental marine toxin poisoning. 4. Pathogenesis of experimental maitotoxin poisoning. Toxicon 27: 978–979

    Google Scholar 

  302. Blythe DG, De Sylva DP, Fleming LE, Ayyar RA, Baden DG, Shrank K (1992) Clinical experience with i.v. mannitol in the treatment of ciguatera. Bull Soc Pathol Exot 85: 425–426

    CAS  PubMed  Google Scholar 

  303. Mattei C, Wen PJ, Nguyen-Huu TD, Alvarez M, Benoit E, Bourdelais AJ, Lewis RJ, Baden DG, Molgó J, Meunier FA (2008) Brevenal inhibits pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells. PLoS ONE 3: e3448.

    Article  PubMed  CAS  Google Scholar 

  304. Munday R (2008) Occurrence and toxicology of palytoxins. In: LM Botana (ed.): Seafood and Freshwater Toxins, Pharmacology, Physiology and Detection, Taylor & Francis Ltd, Boca Raton, FL, 693–713

    Google Scholar 

  305. Hoffmann K, Hermanns-Clausen M, Buhl C, Büchler MW, Schemmer P, Mebs D, Kauferstein S (2008) A case of palytoxin poisoning due to contact with zoantid corals through a skin injury. Toxicon 51: 1535–1537

    Article  CAS  PubMed  Google Scholar 

  306. Ciminiello P, Dell’ Aversano C, Fattorusso E, Forino M, Magno GS, Tartaglione L, Grillo C, Melchiorre N (2006) The Genoa 2005 outbreak. Determination of putative palytoxin in Mediterranean Ostreopsis ovata by a new liquid chromatography tandem mass spectrometry method. Anal Chem 78: 6153–6159

    Article  CAS  PubMed  Google Scholar 

  307. Okano H, Masuoka H, Kamei S, Seko T, Koyabu S, Tsuneoka K, Tamai T, Ueda K, Nakazawa S, Sugawa M, Suzuki H, Watanabe M, Yatani R, Nakano T (1998) Rhabdomyolysis and myocardial damage induced by palytoxin, a toxin of blue humphead parrotfish. Intern Med 37: 330–333

    Article  CAS  PubMed  Google Scholar 

  308. Ito E, Satake M, Ofuji K, Kurita N, McMahon T, James K, Yasumoto T (2000) Multiple organ damage caused by a new toxin azaspiracid, isolated from mussels produced in Ireland. Toxicon 38: 917–930

    Article  CAS  PubMed  Google Scholar 

  309. Ito E, Satake M, Ofuji K, Higashi M, Harigaya K, McMahon T, Yasumoto T (2002) Chronic effects in mice caused by oral administration of sublethal doses of azaspiracid, a new marine toxin isolated from mussels. Toxicon 40: 193–203

    Article  CAS  PubMed  Google Scholar 

  310. EFSA (2009) Marine biotoxins in shellfish — Yessotoxin group, Scientific Opinion of the Panel on Contaminants in the Food chain. EFSA J 907: 1–62

    Google Scholar 

  311. Paolo S, Di Fiore PP (2006) Endocytosis conducts the cell signaling orchestra. Cell 124: 897–900

    Article  CAS  Google Scholar 

  312. Orsi CF, Colombari B, Callegari F, Todaro AM, Ardizzoni A, Rossini GP, Blasi E, Peppoloni S (2009) Yessotoxin inhibits phagocytic activity of macrophages. Toxicon, in press

    Google Scholar 

  313. Larsen K, Petersen D, Wilkins AL, Samdal IA, Sandvik M, Rundberget T, Goldstone D, Arcus V, Hovgaard P, Rise F, Rehmann N, Hess P, Miles CO (2007) Clarification of the C-35 stereochemistries of dinophysistoxin-1 and dinophysistoxin-2, and its consequences for binding to protein phosphatase. Chem Res Toxicol 20: 868–875

    Article  CAS  PubMed  Google Scholar 

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  1. Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Via Campi 287, 41100, Modena, Italy

    Gian Paolo Rossini

  2. Department of Environment, Microbiology and Phycotoxins, IFREMER, 44311, Nantes Cedex 03, France

    Philipp Hess

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  1. Federal Institute for Risk Assessment, Thielallee 88-92, 14195, Berlin, Germany

    Andreas Luch

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Rossini, G.P., Hess, P. (2010). Phycotoxins: chemistry, mechanisms of action and shellfish poisoning. In: Luch, A. (eds) Molecular, Clinical and Environmental Toxicology. Experientia Supplementum, vol 100. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8338-1_3

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