TY - JOUR
T1 - Functional, immunological characterization, and anticancer activity of BaMtx
T2 - A new Lys49- PLA2 homologue isolated from the venom of Peruvian Bothrops atrox snake (Serpentes: Viperidae)
AU - Proleón, Alex
AU - Torrejón, Daniel
AU - Urra, Felix A.
AU - Lazo, Fanny
AU - López-Torres, Camila
AU - Fuentes-Retamal, Sebastián
AU - Quispe, Edwin
AU - Bautista, Lorgio
AU - Agurto, Andrés
AU - Gavilan, Ronnie G.
AU - Sandoval, Gustavo A.
AU - Rodríguez, Edith
AU - Sánchez, Eladio F.
AU - Yarlequé, Armando
AU - Vivas-Ruiz, Dan E.
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - 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.
AB - 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.
KW - Antibody
KW - Bothrops atrox
KW - Breast cancer cells
KW - Lys-49 PLA
KW - Mitochondrial bioenergetics
KW - Myotoxicity
UR - http://www.scopus.com/inward/record.url?scp=85126878763&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2022.03.111
DO - 10.1016/j.ijbiomac.2022.03.111
M3 - Artículo
C2 - 35321814
AN - SCOPUS:85126878763
SN - 0141-8130
VL - 206
SP - 990
EP - 1002
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -