| Author | Naumann, Gustavo Baptista | |
| Author | Silva, Liliana F. | |
| Author | Silva, Luciana Maria | |
| Author | Faria, Gilson | |
| Author | Richardson, Michael | |
| Author | Evangelista, Karla | |
| Author | Kohlhoff, Markus | |
| Author | Gontijo, Celia Maria Ferreira | |
| Author | Navdaev, Alexei | |
| Author | Rezende, Flavia F. de | |
| Author | Eble, Johannes | |
| Author | Sanchez, Eladio Oswaldo Flores | |
| Access date | 2014-11-28T11:54:40Z | |
| Available date | 2014-11-28T11:54:40Z | |
| Document date | 2011 | |
| Citation | NAUMANN, Gustavo Baptista et al. Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom. Biochim Biophys Acta, v. 1810, n. 7, p. 683-694, 2011. | pt_BR |
| ISSN | 0006-3002 | |
| URI | https://www.arca.fiocruz.br/handle/icict/8991 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | open access | pt_BR |
| Title | Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom. | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1016/j.bbagen.2011.04.003 | |
| Abstract | Background : Multifunctional l-amino acid oxidases (LAAOs) occur widely in snake venoms.
Methods : The l-AAO from Bothrops leucurus (Bl-LAAO) venom was purified using a combination of molecular exclusion and ion-exchange chromatographies. We report some biochemical features of Bl-LAAO associated with its effect on platelet function and its cytotoxicity.
Results: Bl-LAAO is a 60 kDa monomeric glycoprotein. Its N-terminal sequence shows high homology to other members of the snake-venom LAAO family. Bl-LAAO catalyzes oxidative deamination of l-amino acids with the generation of H2O2. The best substrates were: l-Met, l-Norleu, l-Leu, l-Phe and l-Trp. The effects of snake venom LAAOs in hemostasis, especially their action on platelet function remain largely unknown. Bl-LAAO dose-dependently inhibited platelet aggregation of both human PRP and washed platelets. Moreover, the purified enzyme exhibited a killing effect in vitro against Leishmania sp., promastigotes, with a very low EC50 of 0.07 μM. Furthermore, the cytotoxicity of Bl-LAAO was observed in the stomach cancer MKN-45, adeno carcinoma HUTU, colorectal RKO and human fibroblast LL-24 cell lines. The enzyme released enough H2O2 in culture medium to induce apoptosis in cells in a dose- and time-dependent manner. The biological effects were inhibited by catalase.
Conclusion: Bl-LAAO, a major component of B. leucurus venom, is a cytotoxin acting primarily via the generation of high amounts of H2O2 which kill the cells.
General significance: These results allow us to consider the use of LAAOs as anticancer agents, as tools in biochemical studies to investigate cellular processes, and to obtain a better understanding of the envenomation mechanism. | pt_BR |
| Affilliation | Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Frankfurt University Hospital. Center for Molecular Medicine. Dept. Vascular Matrix Biology Excellence Cluster CardioPulmonary System. Frankfurt , Germany | pt_BR |
| Affilliation | Frankfurt University Hospital. Center for Molecular Medicine. Dept. Vascular Matrix Biology Excellence Cluster CardioPulmonary System. Frankfurt , Germany | pt_BR |
| Affilliation | Frankfurt University Hospital. Center for Molecular Medicine. Dept. Vascular Matrix Biology Excellence Cluster CardioPulmonary System. Frankfurt , Germany | pt_BR |
| Affilliation | Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brazil | pt_BR |
| Subject | Animal toxin | pt_BR |
| Subject | Bl-LAAO | pt_BR |
| Subject | amino acid oxidase | pt_BR |
| Subject | Platelet function | pt_BR |
| Subject | Apoptosis | pt_BR |
