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Formación de canales iónicos permeables por el factor de necrosis tumoral alfa
B L Kagan1, R L Baldwin, D Munoz
1Department of Psychiatry, School of Medicine, University of California, Los Angeles 90024.
Science (New York, N.Y.)
|March 13, 1992
Resumen
El factor de necrosis tumoral alfa (TNF) puede ejercer sus efectos mediante la formación de canales iónicos. La acidificación induce cambios conformacionales, lo que permite al TNF formar canales dependientes del pH en las bicapas lipídicas y aumentar la permeabilidad de iones celulares.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología celular Biología celular.
- Inmunología Inmunología.
Sus antecedentes:
- El factor de necrosis tumoral alfa (TNF) es una proteína involucrada en estados inflamatorios y de enfermedad.
- Los mecanismos precisos de los efectos citotóxicos y hormonales del TNF no se comprenden completamente.
- El análisis estructural sugiere que los trimers de TNF tienen una región parecida a un poro, lo que insinúa la actividad del canal.
Objetivo del estudio:
- Para investigar la actividad potencial de formación de canales iónicos del TNF.
- Explorar las propiedades estructurales y funcionales del TNF en entornos de lípidos.
- Para determinar si los efectos fisiológicos del TNF están mediados por la formación de canales iónicos.
Principales métodos:
- Análisis del cambio de conformación del TNF tras la acidificación.
- Pruebas de inserción de vesículas lipídicas. ensayos de inserción de vesículas lipídicas.
- Electrofisiología de la bicapa lipídica plana para evaluar la permeabilidad de iones.
- Medición de la permeabilidad del sodio en las células del linfoma U937.
Principales resultados:
- La acidificación indujo cambios conformacionales en el TNF, aumentando la hidrofobidad superficial y la inserción en la membrana.
- El TNF formaba canales iónico-permeables dependientes del pH y dependientes del voltaje en las bicapas de lípidos artificiales.
- El TNF aumentaba la permeabilidad de los iones sodio en las células U937 humanas.
Conclusiones:
- El TNF posee una actividad intrínseca de formación de canales iónicos.
- Esta actividad está influenciada por el pH y el voltaje.
- Los efectos fisiológicos del TNF pueden estar mediados en parte por su función de canal iónico.
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