Skip to main content
SpringerLink
Log in
Book cover

Molecular, Clinical and Environmental Toxicology pp 213–232Cite as

High-molecular weight protein toxins of marine invertebrates and their elaborate modes of action

  • Chapter

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

Abstract

High-molecular weight protein toxins significantly contribute to envenomations by certain marine invertebrates, e.g., jellyfish and fire corals. Toxic proteins frequently evolved from enzymes meant to be employed primarily for digestive purposes. The cellular intermediates produced by such enzymatic activity, e.g., reactive oxygen species or lysophospholipids, rapidly and effectively mediate cell death by disrupting cellular integrity. Membrane integrity may also be disrupted by pore-forming toxins that do not exert inherent enzymatic activity. When targeted to specific pharmacologically relevant sites in tissues or cells of the natural enemy or prey, toxic enzymes or pore-forming toxins even may provoke fast and severe systemic reactions. Since toxin-encoding genes constitute “hot spots” of molecular evolution, continuous variation and acquirement of new pharmacological properties are guaranteed. This also makes individual properties and specificities of complex proteinanceous venoms highly diverse and inconstant. In the present chapter we portray high-molecular weight constituents of venoms present in box jellyfish, sea anemones, sea hares, fire corals and the crown-of-thorns starfish. The focus lies on the latest achievements in the attempt to elucidate their molecular modes of action.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Nakashima K, Nobuhisa I, Deshimaru M, Nakai M, Ogawa T, Shimohigashi Y, Fukumaki Y, Hattori M, Sakaki Y, Hattori S (1995) Accelerated evolution in the protein-coding regions is universal in crotalinae snake venom gland phospholipase A2 isozyme genes. Proc Natl Acad Sci USA 92: 5605–5609

    Article  CAS  PubMed  Google Scholar 

  2. Butzke D (2003) APIT — The cytolytic toxin of ink from Aplysia punctata. PhD Thesis, Free University, Berlin, Germany (online available in German at: http://www.dart-europe.eu/full.php?id=55108)

    Google Scholar 

  3. Pearce LB, First ER, MacCallum RD, Gupta A (1997) Pharmacologic characterization of botulinum toxin for basic science and medicine. Toxicon 35: 1373–1412

    Article  CAS  PubMed  Google Scholar 

  4. Murata M, Naoki H, Matsunaga S, Satake M, Yasumoto T (1994) Structure and partial stereochemical assignments for maitotoxin, the most toxic and largest natural non-biopolymer. J Am Chem Soc 116: 7098–7108

    Article  CAS  Google Scholar 

  5. Montecucco C, Gutierrez JM, Lomonte B (2008) Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: Common aspects of their mechanisms of action. Cell Mol Life Sci 65: 2897–2912

    Article  CAS  PubMed  Google Scholar 

  6. Yotsu-Yamashita M, Urabe D, Asai M, Nishikawa T, Isobe M (2003) Biological activity of 8,11-dideoxytetrodotoxin: Lethality to mice and the inhibitory activity to cytotoxicity of ouabain and veratridine in mouse neuroblastoma cells, Neuro-2a. Toxicon 42: 557–560

    Article  CAS  PubMed  Google Scholar 

  7. Anderluh G, Maček P (2002) Cytolytic peptide and protein toxins from sea anemones (anthozoa: actiniaria). Toxicon 40: 111–124

    Article  CAS  PubMed  Google Scholar 

  8. Bergmann W, Feeney RJ (1951) Contribution to the studies of marine products. XXXII. The nucleosides of sponges. I. J Org Chem 16: 981–987

    Article  CAS  Google Scholar 

  9. Bostock J, Riley HT (1855) The Natural History Pliny the Elder. Taylor and Francis, London, UK (online available at: http://www.perseus.tufts.edu/cgi-bin/ptext?layout=;doc=Perseus%3Atext %3A1999.02.0137,;query=toc;loc=7.24)

    Google Scholar 

  10. Tibballs J (2006) Australian venomous jellyfish, envenomation syndromes, toxins and therapy. Toxicon 48: 830–859

    Article  CAS  PubMed  Google Scholar 

  11. Gershwin LA, Dawes P (2008) Preliminary observations on the response of Chironex fleckeri (cnidaria: cubozoa: chirodropida) to different colors of light. Biol Bull 215: 57–62

    PubMed  Google Scholar 

  12. Rifkin J, Endean R (1983) The structure and function of the nematocysts of Chironex fleckeri Southcott, 1956. Cell Tissue Res 233: 563–577

    Article  CAS  PubMed  Google Scholar 

  13. Endean R, Henderson L (1969) Further studies of toxic material from nematocysts of the cubomedusan Chironex fleckeri Southcott. Toxicon 7: 303–314

    Article  CAS  PubMed  Google Scholar 

  14. Barnes JH (1967) Extraction of cnidarian venom from living tentacle. In: FE Russell, PR Saunders (eds): Animal Toxins, Pergamon Press, Oxford, 115–129

    Google Scholar 

  15. Baxter EH, Marr AG, Lane WR (1968) Immunity to the venom of the sea wasp Chironex fleckeri. Toxicon 6: 45–50

    Article  CAS  PubMed  Google Scholar 

  16. Baxter EH, Marr AG (1969) Sea wasp (Chironex fleckeri) venom: Lethal, haemolytic and dermonecrotic properties. Toxicon 7: 195–210

    Article  CAS  PubMed  Google Scholar 

  17. Barnes JH (1960) Observations on jellyfish stingings in North Queensland. Med J Aust 47: 993–999

    PubMed  Google Scholar 

  18. Underwood AH, Seymour JE (2007) Venom ontogeny, diet and morphology in Carukia barnesi, a species of Australian box jellyfish that causes Irukandji syndrome. Toxicon 49: 1073–1082

    Article  CAS  PubMed  Google Scholar 

  19. Sutherland SK (1983) Australian Animal Toxins: The Creatures, Their Toxins, and Care of the Poisoned Patient. Oxford University Press, Melbourne

    Google Scholar 

  20. Barnes JH (1966) Studies on three venomous cubomedusae. In: WJ Rees (ed.): The Cnidaria and Their Evolution, Academic Press, New York, 307–332

    Google Scholar 

  21. Brinkman D, Burnell J (2008) Partial purification of cytolytic venom proteins from the box jellyfish, Chironex fleckeri. Toxicon 51, 853–863.

    Article  CAS  PubMed  Google Scholar 

  22. Brinkman DL, Burnell JN (2009) Biochemical and molecular characterisation of cubozoan protein toxins. Toxicon, in press

    Google Scholar 

  23. Nagai H, Takuwa K, Nakao M, Ito E, Miyake M, Noda M, Nakajima T (2000) Novel proteinaceous toxins from the box jellyfish (sea wasp) Carybdea rastoni. Biochem Biophys Res Commun 275: 582–588

    Article  CAS  PubMed  Google Scholar 

  24. Nagai H, Takuwa K, Nakao M, Sakamoto B, Crow GL, Nakajima T (2000) Isolation and characterization of a novel protein toxin from the Hawaiian box jellyfish (sea wasp) Carybdea alata. Biochem Biophys Res Commun 275: 589–594

    Article  CAS  PubMed  Google Scholar 

  25. Nagai H, Takuwa-Kuroda K, Nakao M, Oshiro N, Iwanaga S, Nakajima T (2002) A novel protein toxin from the deadly box jellyfish (sea wasp, Habu-kurage) Chiropsalmus quadrigatus. Biosci Biotechnol Biochem 66: 97–102

    Article  CAS  PubMed  Google Scholar 

  26. Chung JJ, Ratnapala LA, Cooke IM, Yanagihara AA (2001) Partial purification and characterization of a hemolysin (CAH1) from Hawaiian box jellyfish (Carybdea alata) venom. Toxicon 39: 981–990

    Article  CAS  PubMed  Google Scholar 

  27. Brinkman D, Burnell J (2007) Identification, cloning and sequencing of two major venom proteins from the box jellyfish, Chironex fleckeri. Toxicon 50: 850–860

    Article  CAS  PubMed  Google Scholar 

  28. Bailey PM, Bakker AJ, Seymour JE, Wilce JA (2005) A functional comparison of the venom of three Australian jellyfish — Chironex fleckeri, Chiropsalmus sp., and Carybdea xaymacana — on cytosolic Ca2+, haemolysis and Artemia sp. lethality. Toxicon 45: 233–242

    Article  CAS  PubMed  Google Scholar 

  29. Watanabe I, Nomura T, Tominaga T, Yamamoto K, Kohda C, Kawamura I, Mitsuyama M (2006) Dependence of the lethal effect of pore-forming haemolysins of Gram-positive bacteria on cytolytic activity. J Med Microbiol 55: 505–510

    Article  CAS  PubMed  Google Scholar 

  30. Edwards LP, Whitter E, Hessinger DA (2002) Apparent membrane pore-formation by Portuguese man-of-war (Physalia physalis) venom in intact cultured cells. Toxicon 40: 1299–1305

    Article  CAS  PubMed  Google Scholar 

  31. Hessinger DA (1988) Nematocyst venoms and toxims. In: DA Hessinger, HM Lenhoff (eds): The Biology of Nematocysts, Academic Press, San Diego, CA, 333–368

    Google Scholar 

  32. Guess HA, Saviteer PL, Morris CR (1982) Hemolysis and acute renal failure following a Portuguese man-of-war sting. Pediatrics 70: 979–981

    CAS  PubMed  Google Scholar 

  33. Spelman FJ, Bowe EA, Watson CB, Klein EE (1982) Acute renal failure as a result of Physalia physalis sting. South Med J 70: 979

    Google Scholar 

  34. Maček P, Lebez D (1988) Isolation and characterization of three lethal and hemolytic toxins from the sea anemone Actinia equina L. Toxicon 26: 441–451

    Article  PubMed  Google Scholar 

  35. Anderluh G, Pungercar J, Krizaj I, Strukelj B, Gubensek F, Maček P (1997) N-terminal truncation mutagenesis of equinatoxin II, a pore-forming protein from the sea anemone Actinia equina. Protein Eng 10: 751–755

    Article  CAS  PubMed  Google Scholar 

  36. Kristan K, Viero G, Dalla Serra M, Maček P, Anderluh G (2009) Molecular mechanism of pore formation by actinoporins. Toxicon, in press

    Google Scholar 

  37. Bunc M, Drevensek G, Budihna M, Suput D (1999) Effects of equinatoxin II from Actinia equina (L.) on isolated rat heart: The role of direct cardiotoxic effects in equinatoxin II lethality. Toxicon 37: 109–123

    Article  CAS  PubMed  Google Scholar 

  38. Suput D (2009) In vivo effects of cnidarian toxins and venoms. Toxicon, in press

    Google Scholar 

  39. Thompson TE, Bennett I (1969) Physalia nematocysts: Utilized by mollusks for defense. Science 166: 1532–1533

    Article  PubMed  CAS  Google Scholar 

  40. Rudman WB (1998) Glaucus atlanticus Forster, 1777. Sea slug forum. Australian Museum, Sydney (online available at: http://www.seaslugforum.net/factsheet.cfm?base=glauatla, accessed 17 Juli 2009)

    Google Scholar 

  41. Carefoot TH (1987) Aplysia: Its biology and ecology. Oceanogr Mar Biol Annu Rev 25: 167–284

    Google Scholar 

  42. Nolen TG, Johnson PM (2001) Defensive inking in Aplysia spp.: Multiple episodes of ink secretion and the adaptive use of a limited chemical response. J Exp Biol 204: 1257–1268

    CAS  PubMed  Google Scholar 

  43. Johnson PM, Kicklighter CE, Schmidt M, Kamio M, Yang H, Elkin D, Michel WC, Tai PC, Derby CD (2006) Packaging of chemicals in the defensive secretory glands of the sea hare Aplysia californica. J Exp Biol 209: 78–88

    Article  CAS  PubMed  Google Scholar 

  44. Kicklighter CE, Shabani S, Johnson PM, Derby CD (2005) Sea hares use novel antipredatory chemical defenses. Curr Biol 15: 549–554

    Article  CAS  PubMed  Google Scholar 

  45. Kicklighter CE, Derby CD (2006) Multiple components in ink of the sea hare Aplysia californica are aversive to the sea anemone Anthopleura sola. J Exp Mar Biol Ecol 334: 256–268

    Article  Google Scholar 

  46. Nolen TG, Johnson PM, Kicklighter CE, Capo T (1995) Ink secretion by the marine snail Aplysia californica enhances its ability to escape from a natural predator. J Comp Physiol A 176: 239–254

    Article  Google Scholar 

  47. Derby CD (2007) Escape by inking and secreting: Marine molluscs avoid predators through a rich array of chemicals and mechanisms. Biol Bull 213: 274–289

    Article  CAS  PubMed  Google Scholar 

  48. Derby CD, Kicklighter CE, Johnson PM, Zhang X (2007) Chemical composition of inks of diverse molluscs suggests convergent chemical defenses. J Chem Ecol 33: 1105–1113

    Article  CAS  PubMed  Google Scholar 

  49. Luesch H, Moore RE, Paul VJ, Mooberry SL, Corbett TH (2001) Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1. J Nat Prod 64: 907–910

    Article  CAS  PubMed  Google Scholar 

  50. Halstead BW (1988) Poisonous and Venomous Marine Animals of the World. 2nd edn., Darwin Press, Princeton, NJ

    Google Scholar 

  51. Sakamoto Y, Nakajima T, Misawa S, Ishikawa H, Itoh Y, Nakashima T, Okanoue T, Kashima K, Tsuji T (1998) Acute liver damage with characteristic apoptotic hepatocytes by ingestion of Aplysia kurodai, a sea hare. Intern Med 37: 927–929

    Article  CAS  PubMed  Google Scholar 

  52. Hino K, Mitsui Y, Hirano Y (1994) Four cases of acute liver damage following the ingestion of a sea hare egg. J Gastroenterol 29: 679

    Article  CAS  PubMed  Google Scholar 

  53. Sorokin M (1988) Human poisoning by ingestion of a sea hare (Dolabella auricularia). Toxicon 26: 1095–1097

    Article  CAS  PubMed  Google Scholar 

  54. Butzke D, Machuy N, Thiede B, Hurwitz R, Goedert S, Rudel T (2004) Hydrogen peroxide produced by Aplysia ink toxin kills tumor cells independent of apoptosis via peroxiredoxin I sensitive pathways. Cell Death Differ 11: 608–617

    CAS  PubMed  Google Scholar 

  55. Butzke D, Hurwitz R, Thiede B, Goedert S, Rudel T (2005) Cloning and biochemical characterization of APIT, a new l-amino acid oxidase from Aplysia punctata. Toxicon 46: 479–489

    Article  CAS  PubMed  Google Scholar 

  56. Hampton MB, Orrenius S (1997) Dual regulation of caspase activity by hydrogen peroxide: Implications for apoptosis. FEBS Lett 414: 552–556

    Article  CAS  PubMed  Google Scholar 

  57. Suhr SM, Kim DS (1996) Identification of the snake venom substance that induces apoptosis. Biochem Biophys Res Commun 224: 134–139

    Article  CAS  PubMed  Google Scholar 

  58. Li R, Zhu S, Wu J, Wang W, Lu Q, Clemetson KJ (2008) l-Amino acid oxidase from Naja atra venom activates and binds to human platelets. Acta Biochim Biophys Sin 40: 19–26

    CAS  PubMed  Google Scholar 

  59. Kini RM (2003) Excitement ahead: Structure, function and mechanism of snake venom phospholipase A2 enzymes. Toxicon 42: 827–840

    Article  CAS  PubMed  Google Scholar 

  60. Stefansson S, Kini RM, Evans HJ (1990) The basic phospholipase A2 from Naja nigricollis venom inhibits the prothrombinase complex by a novel nonenzymatic mechanism. Biochemistry 29: 7742–7746

    Article  CAS  PubMed  Google Scholar 

  61. Rowan EG (2001) What does β-bungarotoxin do at the neuromuscular junction? Toxicon 39: 107–118

    Article  CAS  PubMed  Google Scholar 

  62. Rosenberg P (1986) The relationship between enzymatic activity and pharmacological properties of phospholipases. In: JB Harris (ed.): Natural Toxins, Oxford University Press, Oxford, 129–147

    Google Scholar 

  63. Kini RM, Evans HJ (1987) Structure-function relationships of phospholipases. The anticoagulant region of phospholipases A2. J Biol Chem 262: 14402–14407

    CAS  PubMed  Google Scholar 

  64. Nevalainen TJ, Llewellyn LE, Benzie JAH (2001) Phospholipase A2 in marine invertebrates. Rapp Comm Int Explor Sci Mer Mediterr 36: 202

    Google Scholar 

  65. Nevalainen TJ, Peuravuori HJ, Quinn RJ, Llewellyn LE, Benzie JAH, Fenner PJ, Winkel KD (2004) Phospholipase A2 in cnidaria. Comp Biochem Physiol B139: 731–735

    Article  PubMed  CAS  Google Scholar 

  66. Williamson JA, Fenner PJ, Burnett JW, Rifkin JF (1996) Venomous and Poisonous Marine Animals: A Medical and Biological Handbook. UNSW Press, Sydney

    Google Scholar 

  67. Bachand R (1983) Fire coral — The stingers, Underwater Naturalist 14: 12–15

    Google Scholar 

  68. Radwan FF, Aboul-Dahab HM (2004) Milleporin-1, a new phospholipase A2 active protein from the fire coral Millepora platyphylla nematocysts. Comp Biochem Physiol C Toxicol Pharmacol 139: 267–272

    Article  PubMed  CAS  Google Scholar 

  69. Ibarra-Alvarado C, Garcia JA, Aguilar MB, Rojas A, Falcon A, Heimer de la Cotera EP (2007) Biochemical and pharmacological characterization of toxins obtained from the fire coral Millepora complanata. Comp Biochem Physiol C Toxicol Pharmacol 146: 511–518

    Article  PubMed  CAS  Google Scholar 

  70. Souter DW (2007) The ecology of individual specimens of Acanthaster planci in low density populations. PhD Thesis, University of Queensland, Australia (online available at: http://espace.library. uq.edu.au/view/UQ: 151707)

    Google Scholar 

  71. Vogler C, Benzie J, Lessios H, Barber P, Worheide G (2008) A threat to coral reefs multiplied? Four species of crown-of-thorns starfish. Biol Lett 4: 696–699

    Article  PubMed  Google Scholar 

  72. Brauer RW, Jordan MR, Barnes DJ (1970) Triggering of the stomach eversion reflex of Acanthaster planci by coral extracts. Nature 228: 344–346

    Article  CAS  PubMed  Google Scholar 

  73. Endean R (1973) Population explosion of Acanthaster planci and associated destruction of hermatypic corals in the Indo-West Pacific region. In: OA Jones, R Endean (eds): Biology and Geology of Coral Reefs, Academic Press, New York, 389–438

    Google Scholar 

  74. Motokawa T (1986) Morphology of spines and spine joint in the crown-of-thorns starfish Acanthaster planci (Echinodermata, Asteroida). Zoomorphology 106: 247–253

    Article  Google Scholar 

  75. Carpenter RC (1986) Partitioning herbivory and its effects on coral reef algal communities. Ecol Monogr 56: 345–363

    Article  Google Scholar 

  76. Mebs D (2000) Gifftiere: Ein Handbuch für Biologen, Toxikologen, Ärzte und Apotheker. 2nd edn., Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, 84–86

    Google Scholar 

  77. Mebs D (1991) A myotoxic phospholipase A2 from the crown-of-thorns starfish Acanthaster planci. Toxicon 29: 289–293

    Google Scholar 

  78. Shiomi KA, Kazama A, Shimakura K, Nagashima Y (1998) Purification and properties of phospholipases A2 from the crown-of-thorns starfish (Acanthaster planci) venom. Toxicon 36: 589–599

    Article  CAS  PubMed  Google Scholar 

  79. Karasudani I, Koyama T, Nakandakari S, Aniya Y (1996) Purification of anticoagulant factor from the spine venom of the crown-of-thorns starfish, Acanthaster planci. Toxicon 34: 871–879

    Article  CAS  PubMed  Google Scholar 

  80. Shiomi K, Midorikawa S, Ishida M, Nagashima Y, Nagai H (2004) Plancitoxins, lethal factors from the crown-of-thorns starfish Acanthaster planci, are deoxyribonucleases II. Toxicon 44: 499–506

    Article  CAS  PubMed  Google Scholar 

  81. Ota E, Nagashima Y, Shiomi K, Sakurai T, Kojima C, Waalkes MP, Himeno S (2006) Caspase-independent apoptosis induced in rat liver cells by plancitoxin I, the major lethal factor from the crown-of-thorns starfish Acanthaster planci venom. Toxicon 48: 1002–1010

    Article  CAS  PubMed  Google Scholar 

  82. Sato H, Tsuruta Y, Yamamoto Y, Asato Y, Taira K, Hagiwara K, Kayo S, Iwanaga S, Uezato H (2008) Case of skin injuries due to stings by crown-of-thorns starfish (Acanthaster planci). J Dermatol 35: 162–167

    Article  PubMed  Google Scholar 

  83. Schäfer P, Cymerman IA, Bujnicki JM, Meiss G (2007) Human lysosomal DNase IIα contains two requisite PLD-signature (HxK) motifs: Evidence for a pseudodimeric structure of the active enzyme species. Protein Sci 16: 82–91

    Article  PubMed  CAS  Google Scholar 

  84. The UniProt Consortium (2008) The Universal Protein Resource (UniProtKB/Swiss-Prot Q75 WF2). Nucleic Acids Res 36: 190–195

    Article  CAS  Google Scholar 

  85. Ohara M, Oswald E, Sugai M (2004) Cytolethal distending toxin: A bacterial bullet targeted to nucleus. J Biochem 136: 409–413

    Article  CAS  PubMed  Google Scholar 

  86. Thelestam M, Frisan T (2004) Cytolethal distending toxins. Rev Physiol Biochem Pharmacol 152: 111–133

    Article  CAS  PubMed  Google Scholar 

  87. Elwell CA, Dreyfus LA (2000) DNase I homologous residues in CdtB are critical for cytolethal distending toxin-mediated cell cycle arrest. Mol Microbiol 37: 952–963

    Article  CAS  PubMed  Google Scholar 

  88. Cortes-Bratti X, Chaves-Olarte E, Lagergard T, Thelestam M (2000) Cellular internalization of cytolethal distending toxin from Haemophilus ducreyi. Infect Immun 68: 6903–6911

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Alternatives to Animal Experiments, Federal Institute for Risk Assessment, Thielallee 88-92, 14195, Berlin, Germany

    Daniel Butzke

  2. Department of Product Safety, Center for Alternatives to Animal Experiments, Federal Institute for Risk Assessment, Thielallee 88-92, 14195, Berlin, Germany

    Andreas Luch

Authors
  1. Daniel Butzke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andreas Luch
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

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

    Andreas Luch

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Birkhäuser Verlag/Switzerland

About this chapter

Cite this chapter

Butzke, D., Luch, A. (2010). High-molecular weight protein toxins of marine invertebrates and their elaborate modes of action. 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_6

Download citation

Publish with us

Policies and ethics

Search

Navigation