VII Simposio Internacional de Ciencias Farmacéuticas 2019 "VII SICF" -IV Simposio Internacional "Química de los productos naturales"

VII Simposio Internacional de Ciencias Farmacéuticas 2019

VII SICF

Binding to membrane and cell response of pore-forming toxins from sea anemones: biomedical potentialities

Resumen [ES]

Pore-forming toxins (PFTs) puncture the cell membrane and cause one of the most catastrophic damage to a target cell. Despite this drastic effect, cells have evolved to respond against the damage inflicted by the PFT. This capacity for cellular response depends on the toxin and its concentration, on the properties of the pores and the metabolic status and cell type. Sticholysins I and II (StI / II, Sts) and nigrelysin (Ngr) produced respectively by the sea anemones Stichodactyla helianthus (Caribbean Sea) and Anthopleura nigrescens (Costa Rican Pacific) belong to the actinoporin family. All are highly cytolytic proteins, whose activity lies in the nM concentration range, their Mr ~ 20 kDa, show high pI (> 9.5) and preference sphingomyelin-containing membranes. One of the peculiarities of these toxins is that they are produced in soluble form but readily bind both cell and model membranes where they undergo significant conformational changes leading to the formation of a pore of ~1 nm in hydrodynamic radius. Both membrane binding and permeabilizing capacity depend on the lipid composition of the membrane and its physicochemical properties. Here we show the strategy and the most relevant results in terms of membrane binding, permeabilizing capacity, physical properties of the membrane modulating the activity of these actinoporins through biochemical, biophysical procedures and the study of the activation of intracellular pathways that has allowed to carry out studies envisaging their therapeutical applications in cancer o biotechnological applications.

Resumen [EN]

Pore-forming toxins (PFTs) puncture the cell membrane and cause one of the most catastrophic damage to a target cell. Despite this drastic effect, cells have evolved to respond against the damage inflicted by the PFT. This capacity for cellular response depends on the toxin and its concentration, on the properties of the pores and the metabolic status and cell type. Sticholysins I and II (StI / II, Sts) and nigrelysin (Ngr) produced respectively by the sea anemones Stichodactyla helianthus (Caribbean Sea) and Anthopleura nigrescens (Costa Rican Pacific) belong to the actinoporin family. All are highly cytolytic proteins, whose activity lies in the nM concentration range, their Mr ~ 20 kDa, show high pI (> 9.5) and preference sphingomyelin-containing membranes. One of the peculiarities of these toxins is that they are produced in soluble form but readily bind both cell and model membranes where they undergo significant conformational changes leading to the formation of a pore of ~1 nm in hydrodynamic radius. Both membrane binding and permeabilizing capacity depend on the lipid composition of the membrane and its physicochemical properties. Here we show the strategy and the most relevant results in terms of membrane binding, permeabilizing capacity, physical properties of the membrane modulating the activity of these actinoporins through biochemical, biophysical procedures and the study of the activation of intracellular pathways that has allowed to carry out studies envisaging their therapeutical applications in cancer o biotechnological applications.

Sobre el ponente

Carlos Álvarez

Carlos Álvarez

Flag of Cuba
Información Práctica
No Presencial
Spanish / Español
junio 26, 2019 2:49 p. m.
5 minutos
Restaurante "El Tesico"
Autores
Javier Alvarado
Uris Ross Quincoces
Lohans Pedrera
Fabiola Pazos Santos
Ana M. Hernández
Carmen Soto
Frank Solano
Sheila Cabezas
Aisel Valle
María E. Lanio
Palabras clave
Cancer
Cytolysis
Pore-forming toxins