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.

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 103, p. 25-35, OCT 2017.
• Web of Science Citations: 13

Abstract

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)

• FAPESP's process: 15/00740-0 - Therapeutic potential evaluation of L-amino acid oxidases isolated from snake venoms as antitumor: genotoxicity and gene expression studies
• Grantee: Tássia Rafaella Costa
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
• Grantee: Suely Vilela
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 15/25637-7 - Epigenetic modulation of apoptotic machinery in Bcr-Abl positive cells by BmooLAAO-I and MjTX-I toxins
• Grantee: Sandra Mara Burin de Menezes
• Support type: Scholarships in Brazil - Post-Doctorate