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Caspases 3 y 7: mediadores clave de los eventos mitocondriales de la apoptosis
Saquib A Lakhani1, Ali Masud, Keisuke Kuida
1Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Science (New York, N.Y.)
|February 14, 2006
Resumen
Las caspasas 3 y 7 son cruciales para la muerte celular programada (apoptosis). Los ratones que carecían de estas caspasas efectoras mostraron graves defectos cardíacos y resistencia a la apoptosis, destacando su papel esencial en la supervivencia celular.
Área de la Ciencia:
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
- Genética La genética.
Sus antecedentes:
- La apoptosis es un proceso estrictamente regulado que involucra señales aguas arriba que activan las caspasas efectoras aguas abajo.
- La caspasa 3 y la caspasa 7 son enzimas ejecutoras clave en la vía apoptótica.
Objetivo del estudio:
- Para investigar las funciones in vivo e in vitro de los efectores caspases 3 y 7 en la apoptosis.
- Determinar la necesidad de las caspasas 3 y 7 para el desarrollo cardíaco y los eventos apoptóticos mitocondriales.
Principales métodos:
- Generación de ratones con deficiencia tanto en la caspasa 3 como en la caspasa 7.
- Análisis del desarrollo cardíaco en ratones knockout.
- Evaluación de la resistencia a la apoptosis y la función mitocondrial en los fibroblastos con deficiencia de caspasa.
Principales resultados:
- Los ratones con deficiencia de Caspase 3 y 7 exhibieron letalidad embrionaria con defectos cardíacos graves.
- Los fibroblastos que carecían de ambas caspases eran resistentes a la apoptosis inducida por varios estímulos.
- El potencial de la membrana mitocondrial se conservó, y la translocación nuclear del factor inductor de la apoptosis (AIF) se vio afectada en estas células.
- Los eventos apoptóticos tempranos, incluida la translocación de Bax y la liberación del citocromo c, se retrasaron.
Conclusiones:
- Las caspasas 3 y 7 son mediadores esenciales tanto de la apoptosis mediada por el receptor mitocondrial como de la muerte.
- Estas caspasas efectoras juegan un papel crítico en el inicio de eventos mitocondriales clave durante la apoptosis.
- La ausencia de las caspasas 3 y 7 conduce a defectos de desarrollo, lo que subraya su importancia fisiológica.
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