Functional, immunological characterization, and anticancer activity of BaMtx: A new Lys49- PLA2 homologue isolated from the venom of Peruvian Bothrops atrox snake (Serpentes: Viperidae)

Alex Proleón, Daniel Torrejón, Felix A. Urra, Fanny Lazo, Camila López-Torres, Sebastián Fuentes-Retamal, Edwin Quispe, Lorgio Bautista, Andrés Agurto, Ronnie G. Gavilan, Gustavo A. Sandoval, Edith Rodríguez, Eladio F. Sánchez, Armando Yarlequé, Dan E. Vivas-Ruiz

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)990-1002
Number of pages13
JournalInternational Journal of Biological Macromolecules
Volume206
DOIs
StatePublished - 1 May 2022

Bibliographical note

Funding Information:
We thank Alejandro Barrenechea for her technical assistance. This work was supported by Fondo Nacional de Desarrollo Cient?fico, Tecnol?gico y de Innovaci?n Tecnol?gica (FONDECYT)-Consejo Nacional de Ciencia, Tecnolog?a e Innovaci?n Tecnol?gica (CONCYTEC) Per? (Contrato No. 168-2017-FONDECYT and Contrato No 079-2021-FONDECYT); Vicerrectorado de Investigaci?n y Posgrado ? Universidad Nacional Mayor de San Marcos (Proyectos No B18100081, B18100531); Agencia Nacional de Investigaci?n 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.

Funding 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.

Publisher Copyright:
© 2022 Elsevier B.V.

Keywords

  • Antibody
  • Bothrops atrox
  • Breast cancer cells
  • Lys-49 PLA
  • Mitochondrial bioenergetics
  • Myotoxicity

Fingerprint

Dive into the research topics of 'Functional, immunological characterization, and anticancer activity of BaMtx: A new Lys49- PLA2 homologue isolated from the venom of Peruvian Bothrops atrox snake (Serpentes: Viperidae)'. Together they form a unique fingerprint.

Cite this