A new L-amino acid oxidase from Bothrops jararacussu snake venom: Isolation, partial characterization, and assessment of pro-apoptotic and antiprotozoal activities

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Carone, Sante E. I. ; Costa, Tassia R. ; Burin, Sandra M. ; Cintra, Adelia C. O. ; Zoccal, Karina F. ; Bianchini, Francine J. ; Tucci, Luiz F. F. ; Franco, Joao J. ; Torqueti, Maria R. ; Faccioli, Lucia H. ; de Albuquerque, Sergio ; de Castro, Fabiola A. ; Sampaio, Suely V.

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 103, p. 25-35, OCT 2017.
• Citações Web of Science: 13

Resumo

A new L-amino acid oxidase (LAAO) from Bothrops jararacussu venom (BjussuLAAO-II) was isolated by using a three-step chromatographic procedure based on molecular exclusion, hydrophobicity, and affinity. BjussuLAAO-II is an acidic enzyme with pI = 3.9 and molecular mass = 60.36 kDa that represents 0.3% of the venom proteins and exhibits high enzymatic activity (4884.53 U/mg/mim). We determined part of the primary sequence of BjussuLAAO-II by identifying 96 amino acids, from which 34 compose the N-terminal of the enzyme (ADDRNPLEECFRETDYEEFLEIARNGLSDTDNPK). Multiple alignment of the partial BjussuLAAO-II sequence with LAAOs deposited in the NCBI database revealed high similarity (95-97%) with other LAAOs isolated from Bothrops snake venoms. BjussuLAAO-II exerted a strong antiprotozoal effect against Leishmania amazonensis (IC50 = 4.56 mu g/mL) and Trypanosoma cruzi (IC50 = 4.85 mu g/mL). This toxin also induced cytotoxicity (IC50 = 1.80 mu g/mL) and apoptosis in MCF7 cells (a human breast adenocarcinoma cell line) by activating the intrinsic and extrinsic apoptosis pathways, but were not cytotoxic towards MCF10A cells (a non-tumorigenic human breast epithelial cell line). The results reported herein add important knowledge to the field of Toxinology, especially for the development of new therapeutic agents. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 15/00740-0 - Avaliação do potencial terapêutico de L-aminoácido oxidases isoladas de peçonhas de serpentes como antitumoral: estudos de genotoxicidade e expressão gênica
• Beneficiário: Tássia Rafaella Costa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/25637-7 - Modulação epigenética da maquinaria apoptótica em células Bcr-Abl positivas pelas toxinas BmooLAAO-I e MjTX-I
• Beneficiário: Sandra Mara Burin de Menezes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado