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

Author:
Carone, Sante E.I., Costa, Tássia R., Burin, Sandra M., Cintra, Adélia C.O., Zoccal, Karina F., Bianchini, Francine J., Tucci, Luiz F.F., Franco, João J., Torqueti, Maria R., Faccioli, Lúcia H., Albuquerque, Sérgio de, Castro, Fabíola A. de, Sampaio, Suely V.
Source:
International journal of biological macromolecules 2017 v.103 pp. 25-35
ISSN:
0141-8130
Subject:
Bothrops, Leishmania amazonensis, Trypanosoma cruzi, adenocarcinoma, amino acids, apoptosis, breasts, chromatography, cytotoxicity, databases, enzyme activity, epithelial cells, humans, hydrophobicity, proteins, snakes, venoms
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=60.36kDa that represents 0.3% of the venom proteins and exhibits high enzymatic activity (4884.53U/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=4.56μg/mL) and Trypanosoma cruzi (IC50=4.85μg/mL). This toxin also induced cytotoxicity (IC50=1.80μg/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.
Agid:
5685640