Bothorps atrox is responsible for most of the ophidism cases in Perú. As part of the envenoming, myotoxicity is one of the most recurrent and destructive effects. In this study, a myotoxin, named BaMtx, was purified from B. atrox venom to elucidate its biological, immunological, and molecular characteristics. BaMtx was purified using CM-Sephadex-C-25 ion-exchange resin and SDS-PAGE analysis showed a unique protein band of 13 kDa or 24 kDa under reducing or non-reducing conditions, respectively. cDNA sequence codified a 122-aa mature protein with high homology with other Lys49-PLA2s; modeled structure showed a N-terminal helix, a β-wing region, and a C-terminal random coil. This protein has a poor phospholipase A2 enzymatic activity. BaMtx has myotoxic (DMM = 12.30 ± 0.95 μg) and edema-forming (DEM = 26.00 ± 1.15 μg) activities. Rabbit immunization with purified enzyme produced anti-BaMtx antibodies that reduced 50.28 ± 10.15% of myotoxic activity and showed significant cross-reactivity against B. brazili and B pictus venoms. On the other hand, BaMtx exhibits mild anti-proliferative and anti-migratory effects on breast cancer cells, affecting the ROS and NADH levels, which may reduce mitochondrial respiration. These results contribute to the understanding of B. atrox Lys49-PLA2 effects and establish the anticancer potential de BaMtx.
|Number of pages||13|
|Journal||International Journal of Biological Macromolecules|
|State||Published - 1 May 2022|
Bibliographical noteFunding Information:
We thank Alejandro Barrenechea for her technical assistance. This work was supported by Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica (FONDECYT)- Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica (CONCYTEC) Perú (Contrato No. 168-2017-FONDECYT and Contrato No 079-2021-FONDECYT ); Vicerrectorado de Investigación y Posgrado – Universidad Nacional Mayor de San Marcos (Proyectos No B18100081 , B18100531 ); Agencia Nacional de Investigación y Desarrollo de Chile (ANID) , FONDECYT grant # 11201322 , # Redbio0027 , VID- University of Chile # UI-024/20 , Anillo ATC210097 . CL-T and SF-R thank ANID for PhD fellowship #21221998 and FONDECYT postdoctoral #3210667, respectively.
© 2022 Elsevier B.V.
- Bothrops atrox
- Breast cancer cells
- Lys-49 PLA
- Mitochondrial bioenergetics