A new l-amino acid oxidase from Bothrops jararacussu snake venom: Isolation, partial characterization, and assessment of pro-apoptotic and antiprotozoal activities
| Autor: | Karina F. Zoccal, Francine J. Bianchini, Fabíola Attié de Castro, Tássia R. Costa, Sérgio de Albuquerque, Sandra Mara Burin, Maria Regina Torqueti, Lúcia Helena Faccioli, Adélia Cristina Oliveira Cintra, João José Franco, Sante E. I. Carone, Luiz F. F. Tucci, Suely Vilela Sampaio |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Toxinology medicine.drug_class Antiprotozoal Agents Apoptosis Venom Biology L-Amino Acid Oxidase L-amino-acid oxidase Biochemistry 03 medical and health sciences Structural Biology Crotalid Venoms medicine Animals Humans Bothrops Amino Acid Sequence Cytotoxicity Molecular Biology chemistry.chemical_classification 030102 biochemistry & molecular biology General Medicine biology.organism_classification Amino acid 030104 developmental biology chemistry Snake venom MCF-7 Cells Antiprotozoal |
| Zdroj: | International Journal of Biological Macromolecules. 103:25-35 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2017.05.025 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect