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127 results on '"Kamiguti, Aura S."'

14. Characterization of aspercetin, a platelet aggregating component from the venom of the snake Bothrops asper which induces thrombocytopenia and potentiates metalloproteinase-induced hemorrhage

Author

Rucavado Romero, Alexandra, Soto Morera, Mónica, Kamiguti, Aura S., Theakston, R. David G., Fox, Jay W., Escalante Muñoz, Teresa, and Gutiérrez, José María

Subjects
C-type lectin, Snake venom, Aspercetin, Platelet aggregation, Hemorrhage, Bothrops asper venom, Thrombocytopenia
Abstract

Thrombocytopenia occurs in a number of patients bitten by Bothrops asper, a species responsible for the majority of snakebites in Central America and southern Mexico. In this work we describe the isolation of a new platelet-aggregating protein, named aspercetin, from the venom of B. asper, which induces thrombocytopenia in mice. Isolation was carried out by a combination of ion-exchange chromatography on DEAE-Sepharose and affinity chromatography on Affi-Gel Blue. Aspercetin is a disulfide-linked heterodimer, with a pI of 4.5 and a molecular mass of 29,759 Da, detemined by MALDI-ESI mass spectrometry. N-terminal sequence shows homology with a number of venom proteins which belong to the C-type lectin family. Aspercetin has functional similarities with botrocetin, from B. jararaca venom, since it induces platelet aggregation only in the presence of plasma or purified von Willebrand factor. Aspercetin-mediated platelet aggregation results from the interaction of von Willebrand factor with platelet receptor GPIb. Aspercetin lacks anticoagulant effect and does not agglutinate erythrocytes, in contrast with other representatives of the C-type lectin family isolated from snake venoms. Moreover, aspercetin is not lethal, nor does it induce myonecrosis, hemorrhage and edema. When injected intravenously or intramuscularly in mice it induces a rapid, dose-dependent drop in platelet counts and prolongs the bleeding time, suggesting that it may play a role in the thrombocytopenia that develops in a number of B. asper envenomations. Moreover, mice injected intravenously with aspercetin and then receiving an intradermal injection of B. asper hemorrhagic metalloproteinase BaP1 develop a larger hemorrhagic lesion than mice receiving only BaP1. This suggests that aspercetin, by reducing platelet numbers, may contribute to the hemorrhagic effect characteristic of B. asper envenomations. International Foundation for Science/[F2707-2]/IFS/Suecia Universidad de Costa Rica /[741-98-505]/UCR/Costa Rica UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)

Published
2001

16. Isolation and characterization of cotiaractivase, a novel low molecular weight prothrombin activator from the venom of Bothrops cotiara

Author

Senis, Yotis A., primary, Kim, Paul Y., additional, Fuller, Gemma L.J., additional, García, Ángel, additional, Prabhakar, Sripadi, additional, Wilkinson, Mark C., additional, Brittan, Helen, additional, Zitzmann, Nicole, additional, Wait, Robin, additional, Warrell, David A., additional, Watson, Steve P., additional, Kamiguti, Aura S., additional, Theakston, R. David G., additional, Nesheim, Michael E., additional, and Laing, Gavin D., additional

Published
2006
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19. Clinical trial of two antivenoms for the treatment of Bothrops and Lachesis bites in the north eastern Amazon region of Brazil

Author

Pardal, Pedro Pereira de Oliveira, primary, Souza, Suzana Medeiro, additional, Monteiro, Maria Rita de Cássia da Costa, additional, Fan, Hui Wen, additional, Cardoso, João Luiz Costa, additional, França, Francisco Oscar Siqueira, additional, Tomy, Sandra Corrallo, additional, Sano-Martins, Ida S, additional, de Sousa-e-Silva, Maria Cristina Cirillo, additional, Colombini, Mônica, additional, Kodera, Nancy F, additional, Moura-da-Silva, Ana Maria, additional, Cardoso, Diva Ferreira, additional, Velarde, David Toledo, additional, Kamiguti, Aura S, additional, Theakston, Robert David G, additional, and Warrell, David A, additional

Published
2004
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20. Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue‐damaging activities

Author

Watanabe, Leandra, primary, Shannon, John D., additional, Valente, Richard H., additional, Rucavado, Alexandra, additional, Alape‐Girón, Alberto, additional, Kamiguti, Aura S., additional, Theakston, R. David G., additional, Fox, Jay W., additional, Gutiérrez, José María, additional, and Arni, Raghuvir K., additional

Published
2003
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31. Neurotoxicity, anticoagulant activity and evidence of rhabdomyolysis in patients bitten by death adders (Acanthophis sp.) in Southern Papua New Guinea

Author

Lalloo, David G., primary, Trevett, Andrew J., additional, Black, Julie, additional, Mapao, James, additional, Saweri, Adolf, additional, Naraqi, Sirus, additional, Owens, Dale, additional, Kamiguti, Aura S., additional, Hutton, Ronald A., additional, Theakston, R.David G., additional, and Warrell, David A., additional

Published
1996
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41. research paper The role of matrix metalloproteinase  9 in the pathogenesis of chronic lymphocytic leukaemia.

Author

Kamiguti, Aura S., Lee, Edwin S., Till, Kathleen J., Harris, Robert J., Glenn, Mark A., Ke Lin, Mark A., Hai Juan Chen, Mark A., Zuzel, Mirko, and Cawley, John C.

Subjects
*LYMPHOCYTIC leukemia, *METALLOPROTEINASES, *CARCINOGENESIS, *LYMPHOCYTES, *SECRETION, *ENZYMES
Abstract

Matrix metalloproteinases (MMPs) are important for the pathogenesis and progression of different tumours. MMPs-2 and -9 are the principal MMPs produced by lymphocytes; these enzymes can degrade a number of matrix proteins but are the two main MMPs that digest type IV collagen, the major component of basement membranes. Therefore, these enzymes are potentially important for tissue invasion and remodelling by malignant lymphocytes. This study showed that chronic lymphocytic leukaemia (CLL) cells produce and secrete variable amounts of pro-MMP-9, but no MMP-2 or tissue inhibitor of metalloproteinase  1 (TIMP-1). The pro-enzyme was found in monomeric and dimeric forms and also complexed with lipocalin. Moreover, a small fraction of secreted monomer became associated with the cell surface and activated upon cell adhesion to insolubilized type IV collagen. High levels of intracellular MMP-9 were associated with advanced (stage C) disease and with poor patient survival. Immunohistochemical studies demonstrated that MMP-9 was associated with areas of tissue invasion and remodelling. The relatively specific MMP-9 inhibitors, Ro31-9790 (3 μmol/l) and TIMP-1, reduced CLL-cell migration through type IV collagen and through endothelial monolayers suggesting that the enzyme may also be important in malignant cell entry and egress to and from involved tissue. Our data raise the possibility that MMP-9 modulation may have therapeutic potential in advanced CLL. [ABSTRACT FROM AUTHOR]

Published
2004
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42. The Platelet Antigens CD9, CD42 and Integrin αIIbβIIIa Can be Topographically Associated and Transduce Functionally Similar Signals.

Author

Slupsky, Joseph R., Kamiguti, Aura S., Rhodes, Nicholas P., Cawley, John C., Shaw, Andrew R. F., and Zuzel, Mirko

Subjects
*BLOOD platelets, *MOLECULES, *AMINO acids, *TYROSINE, *ANTIGENS, *IMMUNITY, *IMMUNOGLOBULINS
Abstract

Investigation of the specific effects of different mAb known to stimulate platelets (agonist mAb) is complicated by interaction of the Fc portion of these mAb with the platelet FcγRII. This has led to the conclusion that nearly all agonist-mAb-induced activation of platelets is mediated by this receptor. However, the target antigen-mediated signal can be analysed provided that the effects of FcγRII engagement can either be reduced or eliminated. We have therefore blocked platelet Fcγ RII with IV.3 Fab fragments (an anti-Fcγ RII mAb), and stimulated the platelets by cross-linking intact agonist mAb with F(ab′)2 fragments of an Fc-specific anti-mouse antibody. By analysing functional platelet responses and protein-tyrosine phosphorylation, we found that such non-Fcγ RII-mediated cross-linking of CD9, CD42 and glycoprotein (gp) Ilb/IIIa generates closely similar signals. Since this may indicate molecular associations, we analyzed the surface topography of platelets using the chemical cross-linking agent dithiobis(sulfosuccinimidyl propionate). We found that a proportion of CD9, gpIIb/IIIa and CD42 molecules associate with each other on the platelet surface membrane. Thus, our results suggest that these antigens are able to form a larger molecular complex and induce similar signals. Furthermore, cross-linking of CD9 and CD42 stimulated thrombasthenic platelets completely lacking gplIb/IIIa. These data therefore indicate that CD9 and CD42 can signal independently of gpIIb/IIIa, and that signals generated by all these molecules may converge on a common pathway. [ABSTRACT FROM AUTHOR]

Published
1997
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44. Jararhagin ECD-Containing Disintegrin Domain: Expression in Escherichia coliand Inhibition of the Platelet–Collagen Interaction

Author

Moura-da-Silva, Ana M, Lı́nica, Alex, Della-Casa, Maisa S, Kamiguti, Aura S, Ho, Paulo L, Crampton, Julian M, and Theakston, R.David G

Abstract

Jararhagin, a hemorrhagin from Bothrops jararacavenom, is a soluble snake venom component comprising metalloproteinase and disintegrin cysteine-rich domains and, therefore, is structurally closely related to the membrane-bound ADisintegrin And Metalloproteinase (ADAMs) protein family. Its hemorrhagic activity is associated with the effects of both metalloproteinase and disintegrin domains; the metalloproteinase enzymatically damages the endothelium and the disintegrin domain inhibits platelet–collagen interactions. The expression of whole jararhagin or its disintegrin domain has never been attempted before. The aim of this study was to investigate whether we could express the disintegrin domain of jararhagin and to verify whether this domain displays an inhibitory effect on the platelet–collagen interaction. Therefore, the cDNA fragment coding for the disintegrin plus cysteine-rich domains of jararhagin was cloned into the pET32a vector, used to transform the Escherichia coliAD494(DE3)pLysS strain. The thioredoxin–disintegrin fusion protein was recovered from the soluble extract of the cells, yielding up to 50 mg/liter culture. The fusion protein was isolated using polyhistidine binding resin which resulted in a main band of 45 kDa recognized by anti-native jararhagin antibodies. Antibodies raised in rabbits against the fusion protein had high enzyme-linked immunosorbent assay titers against native jararhagin and detected a band of 52 kDa on Western blots of whole B. jararacavenom demonstrating that these antibodies recognize the parent jararhagin molecule. Treatment of the fusion protein with enterokinase, followed by further capture of the enzyme, resulted in a band of 30 kDa, the expected size for jararhagin-C. Further purification of the cleaved disintegrin using FPLC Mono-Q columns resulted in one fraction capable of efficiently inhibiting collagen-induced platelet aggregation in a dose-dependent manner (IC50of 8.5 μg/ml).

Published
1999
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45. Proteolytic Cleavage of the β1Subunit of Platelet α2β1Integrin by the Metalloproteinase Jararhagin Compromises Collagen-stimulated Phosphorylation of pp72 syk*

Author

Kamiguti, Aura S., Markland, Francis S., Zhou, Qing, Laing, Gavin D., Theakston, R. David G., and Zuzel, Mirko

Abstract

Early signaling events in the stimulation of platelets by collagen include the tyrosine phosphorylations of FcR γ-chain, pp72 sykand phospholipase Cγ2. These events are dependent on the main platelet collagen receptor, α2β1integrin (glycoprotein Ia-IIa complex). We recently found that jararhagin, a 52-kDa snake venom metalloproteinase, selectively inhibits collagen-induced platelet secretion and aggregation in parallel with the cleavage of the β1subunit of the α2β1integrin. The present study demonstrates that jararhagin also interferes with collagen-induced phosphorylation of the protein-tyrosine kinase pp72 syk. This effect is not observed when the platelet aggregation response to collagen is inhibited by two venom RGD-containing disintegrins, contortrostatin and echistatin. These disintegrins inhibit platelet aggregation through their high affinity binding to the platelet αIIbβ3integrin (glycoprotein IIb-IIIa complex). We also show that mild stimulation by ADP of jararhagin-treated platelets, but not of platelets treated with the RGD-containing disintegrins, restores the collagen-induced platelet aggregation. ADP also restored both pp72 sykand pleckstrin phosphorylation of jararhagin-treated platelets in response to collagen, presumably via interaction of collagen with ADP-activated αIIbβ3integrin. Thus, RGD-containing disintegrins do not interfere with agonist-induced pp72 sykphosphorylation but inhibit aggregation through occupancy of the αIIbβ3integrin. Conversely, jararhagin affects early platelet signaling events in response to collagen through its effects on the α2β1integrin without interfering with the function of the αIIbβ3integrin. Our demonstration that the degradation of the β1subunit of α2β1by jararhagin results in the loss of pp72 sykphosphorylation, suggests that this subunit is critically involved in collagen-induced platelet signaling.

Published
1997
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