Thioredoxin and its reductase are present on synaptic vesicles, and their inhibition prevents the paralysis induced by botulinum neurotoxins

Cell Reports

Volumn 8, Issue 6, 2014, Pages 1870-1878

  Pirazzini, Marco ^a   Tehran, Domenico Azarnia ^a   Zanetti, Giulia ^a   Megighian, Aram ^a   Scorzeto, Michele ^a   Fillo, Silvia ^b   Shone, Clifford C ^c   Binz, Thomas ^d   Rossetto, Ornella ^a   Lista, Florigio ^b   Montecucco, Cesare ^a  

^a UNIVERSITY OF PADOVA   (Italy)

^b Army Medical and Veterinary Research Center   (Italy)

^c PUBLIC HEALTH ENGLAND   (United Kingdom)

^d HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS ACTING ON THE PERIPHERAL NERVOUS AND NEUROMUSCULAR SYSTEMS; AURANOFIN; BOTULINUM TOXIN; BOTULINUM TOXIN A; BOTULINUM TOXIN C; BOTULINUM TOXIN E; CURCUMIN; EBSELEN; JUGLONE; MYRICETIN; PX 12; SYNAPTOSOMAL ASSOCIATED PROTEIN 25; THIOREDOXIN; THIOREDOXIN INHIBITOR; THIOREDOXIN REDUCTASE; UNCLASSIFIED DRUG; DISULFIDE; ENZYME INHIBITOR; IMIDAZOLE DERIVATIVE; IV 2 COMPOUND;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOSOL; ENDPLATE POTENTIAL; EXCITATORY POSTSYNAPTIC POTENTIAL; MALE; MOTONEURON; MOUSE; NERVE ENDING; NEUROMUSCULAR SYNAPSE; NONHUMAN; OXIDATION REDUCTION REACTION; PARALYSIS; RAT; SOLEUS MUSCLE; SYNAPSE VESICLE; ANIMAL; ANTAGONISTS AND INHIBITORS; BRAIN CORTEX; CYTOPLASM; DRUG EFFECTS; ENZYME ACTIVATION; ENZYMOLOGY; METABOLISM; NERVE CELL; SEROTYPING;

ANIMALS; BOTULINUM TOXINS; CEREBRAL CORTEX; CURCUMIN; CYTOPLASM; DISULFIDES; ENZYME ACTIVATION; ENZYME INHIBITORS; IMIDAZOLES; MALE; MICE; NEURONS; PARALYSIS; SEROTYPING; SYNAPTIC VESICLES; SYNAPTOSOMAL-ASSOCIATED PROTEIN 25; THIOREDOXIN-DISULFIDE REDUCTASE; THIOREDOXINS;

EID: 84907398838     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2014.08.017     Document Type: Article

References (68)

1. Antonucci F., Rossi C., Gianfranceschi L., Rossetto O., Caleo M. Long-distance retrograde effects of botulinum neurotoxin A. J.Neurosci. 2008, 28:3689-3696.
2. Aoki K.R. A comparison of the safety margins of botulinum neurotoxin serotypes A, B, and F in mice. Toxicon 2001, 39:1815-1820.
3. Aras M., Altaş M., Meydan S., Nacar E., Karcioğlu M., Ulutaş K.T., Serarslan Y. Effects of Ebselen on ischemia/reperfusion injury in rat brain. Int. J. Neurosci. 2014, Published online January 10, 2014. 10.3109/00207454.2013.879581.
4. Arnér E.S., Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur. J. Biochem. 2000, 267:6102-6109.
5. Baker A.F., Adab K.N., Raghunand N., Chow H.H.S., Stratton S.P., Squire S.W., Boice M., Pestano L.A., Kirkpatrick D.L., Dragovich T. A phase IB trial of 24-hour intravenous PX-12, a thioredoxin-1 inhibitor, in patients with advanced gastrointestinal cancers. Invest. New Drugs 2013, 31:631-641.
6. Berndt C., Lillig C.H., Holmgren A. Thioredoxins and glutaredoxins as facilitators of protein folding. Biochim. Biophys. Acta 2008, 1783:641-650.
7. Binz T., Rummel A. Cell entry strategy of clostridial neurotoxins. J.Neurochem. 2009, 109:1584-1595.
8. Boyken J., Grønborg M., Riedel D., Urlaub H., Jahn R., Chua J.J. Molecular profiling of synaptic vesicle docking sites reveals novel proteins but few differences between glutamatergic and GABAergic synapses. Neuron 2013, 78:285-297.
9. Braun J.E., Scheller R.H. Cysteine string protein, a DnaJ family member, is present on diverse secretory vesicles. Neuropharmacology 1995, 34:1361-1369.
10. Broide R.S., Rubino J., Nicholson G.S., Ardila M.C., Brown M.S., Aoki K.R., Francis J. The rat Digit Abduction Score (DAS) assay: a physiological model for assessing botulinum neurotoxin-induced skeletal muscle paralysis. Toxicon 2013, 71:18-24.
11. Cai W., Zhang L., Song Y., Wang B., Zhang B., Cui X., Hu G., Liu Y., Wu J., Fang J. Small molecule inhibitors of mammalian thioredoxin reductase. Free Radic. Biol. Med. 2012, 52:257-265.
12. Possession, use, and transfer of select agents and toxins; biennial review. Final rule. Fed. Regist. 2012, 77:61083-61115. CDC (Centers for Disease Control and Prevention), Department of Health and Human Services (HHS).
13. Colasante C., Rossetto O., Morbiato L., Pirazzini M., Molgó J., Montecucco C. Botulinum neurotoxin type A is internalized and translocated from small synaptic vesicles at the neuromuscular junction. Mol. Neurobiol. 2013, 48:120-127.
14. Davletov B., Bajohrs M., Binz T. Beyond BOTOX: advantages and limitations of individual botulinum neurotoxins. Trends Neurosci. 2005, 28:446-452.
15. De Camilli P., Harris S.M., Huttner W.B., Greengard P. Synapsin I (Protein I), a nerve terminal-specific phosphoprotein. II. Its specific association with synaptic vesicles demonstrated by immunocytochemistry in agarose-embedded synaptosomes. J.Cell Biol. 1983, 96:1355-1373.
16. Dekker C., Willison K.R., Taylor W.R. On the evolutionary origin of the chaperonins. Proteins 2011, 79:1172-1192.
17. Dolly J.O., Black J., Williams R.S., Melling J. Acceptors for botulinum neurotoxin reside on motor nerve terminals and mediate its internalization. Nature 1984, 307:457-460.
18. Dressler D. Clinical applications of botulinum toxin. Curr. Opin. Microbiol. 2012, 15:325-336.
19. Eleopra R., Tugnoli V., Rossetto O., Montecucco C., De Grandis D. Botulinum neurotoxin serotype C: a novel effective botulinum toxin therapy in human. Neurosci. Lett. 1997, 224:91-94.
20. Fagan R.P., McLaughlin J.B., Middaugh J.P. Persistence of botulinum toxin in patients' serum: Alaska, 1959-2007. J.Infect. Dis. 2009, 199:1029-1031.
21. Fang J., Lu J., Holmgren A. Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. J.Biol. Chem. 2005, 280:25284-25290.
22. Fischer A., Montal M. Crucial role of the disulfide bridge between botulinum neurotoxin light and heavy chains in protease translocation across membranes. J.Biol. Chem. 2007, 282:29604-29611.
23. Fischer A., Montal M. Molecular dissection of botulinum neurotoxin reveals interdomain chaperone function. Toxicon 2013, 75:101-107.
24. Fykse E.M., Takei K., Walch-Solimena C., Geppert M., Jahn R., De Camilli P., Südhof T.C. Relative properties and localizations of synaptic vesicle protein isoforms: the case of the synaptophysins. J.Neurosci. 1993, 13:4997-5007.
25. Hallett M., Albanese A., Dressler D., Segal K.R., Simpson D.M., Truong D., Jankovic J. Evidence-based review and assessment of botulinum neurotoxin for the treatment of movement disorders. Toxicon 2013, 67:94-114.
26. Hanschmann E.M., Godoy J.R., Berndt C., Hudemann C., Lillig C.H. Thioredoxins, glutaredoxins, and peroxiredoxins-molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling. Antioxid. Redox Signal. 2013, 19:1539-1605.
27. Harper C.B., Martin S., Nguyen T.H., Daniels S.J., Lavidis N.A., Popoff M.R., Hadzic G., Mariana A., Chau N., McCluskey A., et al. Dynamin inhibition blocks botulinum neurotoxin type A endocytosis in neurons and delays botulism. J.Biol. Chem. 2011, 286:35966-35976.
28. Hill K.K., Smith T.J. Genetic diversity within Clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes. Curr. Top. Microbiol. Immunol. 2013, 364:1-20.
29. Holmgren A. Thioredoxin. Annu. Rev. Biochem. 1985, 54:237-271.
30. Holmgren A. Thioredoxin and glutaredoxin systems. J.Biol. Chem. 1989, 264:13963-13966.
31. Holmgren A., Lu J. Thioredoxin and thioredoxin reductase: current research with special reference to human disease. Biochem. Biophys. Res. Commun. 2010, 396:120-124.
32. Ingles-Prieto A., Ibarra-Molero B., Delgado-Delgado A., Perez-Jimenez R., Fernandez J.M., Gaucher E.A., Sanchez-Ruiz J.M., Gavira J.A. Conservation of protein structure over four billion years. Structure 2013, 21:1690-1697.
33. Johnson E.A., Montecucco C. Botulism. Handb. Clin. Neurol. 2008, 91:333-368.
34. Kirkpatrick D.L., Kuperus M., Dowdeswell M., Potier N., Donald L.J., Kunkel M., Berggren M., Angulo M., Powis G. Mechanisms of inhibition of the thioredoxin growth factor system by antitumor 2-imidazolyl disulfides. Biochem. Pharmacol. 1998, 55:987-994.
35. Kumaran D., Eswaramoorthy S., Furey W., Navaza J., Sax M., Swaminathan S. Domain organization in Clostridium botulinum neurotoxin type E is unique: its implication in faster translocation. J.Mol. Biol. 2009, 386:233-245.
36. Lacy D.B., Tepp W., Cohen A.C., DasGupta B.R., Stevens R.C. Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat. Struct. Biol. 1998, 5:898-902.
37. Lu J., Holmgren A. Selenoproteins. J.Biol. Chem. 2009, 284:723-727.
38. Lu J., Holmgren A. Thioredoxin system in cell death progression. Antioxid. Redox Signal. 2012, 17:1738-1747.
39. Lu J., Papp L.V., Fang J., Rodriguez-Nieto S., Zhivotovsky B., Holmgren A. Inhibition of Mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. Cancer Res. 2006, 66:4410-4418.
40. Madeira J.M., Gibson D.L., Kean W.F., Klegeris A. The biological activity of auranofin: implications for novel treatment of diseases. Inflammopharmacology 2012, 20:297-306.
41. Mahmood D.F., Abderrazak A., El Hadri K., Simmet T., Rouis M. The thioredoxin system as a therapeutic target in human health and disease. Antioxid. Redox Signal. 2013, 19:1266-1303.
42. Masuyer G., Chaddock J.A., Foster K.A., Acharya K.R. Engineered botulinum neurotoxins as new therapeutics. Annu. Rev. Pharmacol. Toxicol. 2014, 54:27-51.
43. Matteoli M., Verderio C., Rossetto O., Iezzi N., Coco S., Schiavo G., Montecucco C. Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons. Proc. Natl. Acad. Sci. USA 1996, 93:13310-13315.
44. Meotti F.C., Borges V.C., Zeni G., Rocha J.B.T., Nogueira C.W. Potential renal and hepatic toxicity of diphenyl diselenide, diphenyl ditelluride and Ebselen for rats and mice. Toxicol. Lett. 2003, 143:9-16.
45. Molgo J., Comella J.X., Angaut-Petit D., Pecot-Dechavassine M., Tabti N., Faille L., Mallart A., Thesleff S. Presynaptic actions of botulinal neurotoxins at vertebrate neuromuscular junctions. J.Physiol. (Paris) 1990, 84:152-166.
46. Montal M. Botulinum neurotoxin: a marvel of protein design. Annu. Rev. Biochem. 2010, 79:591-617.
47. Montecucco C., Molgó J. Botulinal neurotoxins: revival of an old killer. Curr. Opin. Pharmacol. 2005, 5:274-279.
48. Morbiato L., Carli L., Johnson E.A., Montecucco C., Molgó J., Rossetto O. Neuromuscular paralysis and recovery in mice injected with botulinum neurotoxins A and C. Eur. J. Neurosci. 2007, 25:2697-2704.
49. Morciano M., Burré J., Corvey C., Karas M., Zimmermann H., Volknandt W. Immunoisolation of two synaptic vesicle pools from synaptosomes: a proteomics analysis. J.Neurochem. 2005, 95:1732-1745.
50. Morciano M., Beckhaus T., Karas M., Zimmermann H., Volknandt W. The proteome of the presynaptic active zone: from docked synaptic vesicles to adhesion molecules and maxi-channels. J.Neurochem. 2009, 108:662-675.
51. Mukherjee A., Martin S.G. The thioredoxin system: a key target in tumour and endothelial cells. Br. J. Radiol. 2008, 81:S57-S68.
52. Naumann M., Dressler D., Hallett M., Jankovic J., Schiavo G., Segal K.R., Truong D. Evidence-based review and assessment of botulinum neurotoxin for the treatment of secretory disorders. Toxicon 2013, 67:141-152.
53. Omata Y., Folan M., Shaw M., Messer R.L., Lockwood P.E., Hobbs D., Bouillaguet S., Sano H., Lewis J.B., Wataha J.C. Sublethal concentrations of diverse gold compounds inhibit mammalian cytosolic thioredoxin reductase (TrxR1). Toxicol. InVitro 2006, 20:882-890.
54. Pantano S., Montecucco C. The blockade of the neurotransmitter release apparatus by botulinum neurotoxins. Cell. Mol. Life Sci. 2014, 71:793-811.
55. Pirazzini M., Bordin F., Rossetto O., Shone C.C., Binz T., Montecucco C. The thioredoxin reductase-thioredoxin system is involved in the entry of tetanus and botulinum neurotoxins in the cytosol of nerve terminals. FEBS Lett. 2013, 587:150-155.
56. Rackham O., Shearwood A.-M.J., Thyer R., McNamara E., Davies S.M.K., Callus B.A., Miranda-Vizuete A., Berners-Price S.J., Cheng Q., Arnér E.S.J., Filipovska A. Substrate and inhibitor specificities differ between human cytosolic and mitochondrial thioredoxin reductases: Implications for development of specific inhibitors. Free Radic. Biol. Med. 2011, 50:689-699.
57. Ramanathan R.K., Abbruzzese J., Dragovich T., Kirkpatrick L., Guillen J.M., Baker A.F., Pestano L.A., Green S., Von Hoff D.D. A randomized phase II study of PX-12, an inhibitor of thioredoxin in patients with advanced cancer of the pancreas following progression after a gemcitabine-containing combination. Cancer Chemother. Pharmacol. 2011, 67:503-509.
58. Rigobello M.P., Bindoli A. Mitochondrial thioredoxin reductase purification, inhibitor studies, and role in cell signaling. Methods Enzymol. 2010, 474:109-122.
59. Rossetto O., Morbiato L., Caccin P., Rigoni M., Montecucco C. Presynaptic enzymatic neurotoxins. J.Neurochem. 2006, 97:1534-1545.
60. Rossetto O., Pirazzini M., Montecucco C. Botulinum neurotoxins: genetic, structural and mechanistic insights. Nat. Rev. Microbiol. 2014, 12:535-549. 10.1038/nrmicro3295.
61. Rozell B., Hansson H.A., Luthman M., Holmgren A. Immunohistochemical localization of thioredoxin and thioredoxin reductase in adult rats. Eur. J. Cell Biol. 1985, 38:79-86.
62. Schiavo G., Santucci A., Dasgupta B.R., Mehta P.P., Jontes J., Benfenati F., Wilson M.C., Montecucco C. Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds. FEBS Lett. 1993, 335:99-103.
63. Sheth A.N., Wiersma P., Atrubin D., Dubey V., Zink D., Skinner G., Doerr F., Juliao P., Gonzalez G., Burnett C., et al. International outbreak of severe botulism with prolonged toxemia caused by commercial carrot juice. Clin. Infect. Dis. 2008, 47:1245-1251.
64. Sons M.S., Busche N., Strenzke N., Moser T., Ernsberger U., Mooren F.C., Zhang W., Ahmad M., Steffens H., Schomburg E.D., et al. alpha-Neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction. Neuroscience 2006, 138:433-446.
65. Stemme S., Hansson H.A., Holmgren A., Rozell B. Axoplasmic transport of thioredoxin and thioredoxin reductase in rat sciatic nerve. Brain Res. 1985, 359:140-146.
66. Takamori S., Holt M., Stenius K., Lemke E.A., Grønborg M., Riedel D., Urlaub H., Schenck S., Brügger B., Ringler P., et al. Molecular anatomy of a trafficking organelle. Cell 2006, 127:831-846.
67. Yamaguchi T., Sano K., Takakura K., Saito I., Shinohara Y., Asano T., Yasuhara H. Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Stroke 1998, 29:12-17. Ebselen Study Group.
68. Zhao R., Masayasu H., Holmgren A. Ebselen: a substrate for human thioredoxin reductase strongly stimulating its hydroperoxide reductase activity and a superfast thioredoxin oxidant. Proc. Natl. Acad. Sci. USA 2002, 99:8579-8584.