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Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry
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La proteína adaptadora p66shc controla la respuesta al estrés oxidativo y la esperanza de vida en los mamíferos
E Migliaccio1, M Giorgio, S Mele
1Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Nature
|December 2, 1999
Resumen
Dirigirse al gen p66shc en ratones mejora la resistencia celular al estrés y aumenta significativamente su esperanza de vida. Este descubrimiento arroja luz sobre los mecanismos de respuesta al estrés de los mamíferos y los procesos de envejecimiento.
Área de la Ciencia:
- Biología celular Biología celular.
- Genética La genética.
- Gerontología Gerontología.
Sus antecedentes:
- Las mutaciones genéticas en los invertebrados pueden extender la vida útil y mejorar la resistencia al estrés.
- Los mecanismos de respuesta al estrés de los mamíferos y la regulación de la esperanza de vida no se comprenden bien.
- No se ha demostrado que ningún gen conocido en mamíferos aumente la esperanza de vida individual.
Objetivo del estudio:
- Para investigar el papel del gen p66shc en la respuesta al estrés de los mamíferos y la esperanza de vida.
- Para determinar si la mutación p66shc afecta la resistencia celular a las tensiones ambientales.
- Explorar el potencial de p66shc como regulador del envejecimiento en mamíferos.
Principales métodos:
- La mutación dirigida del gen p66shc del ratón.
- Evaluación de la apoptosis celular y la resistencia al estrés (H2O2, luz UV, paraquat).
- Análisis de las vías de respuesta al estrés p53 y p21 en las células knockout p66shc.
- La medición de la esperanza de vida en ratones p66shc knockout.
Principales resultados:
- p66shc es serina fosforilada en respuesta al estrés oxidativo y UV.
- La ablación de p66shc mejora la resistencia celular a la apoptosis.
- Las células knockout p66shc muestran un deterioro de las respuestas al estrés p53 y p21.
- Los ratones p66shc knockout exhiben una mayor resistencia al paraquat y una vida útil un 30% más larga.
Conclusiones:
- p66shc juega un papel crítico en la apoptosis inducida por el estrés en mamíferos.
- El gen p66shc es un componente clave de una vía de transducción de señales que regula la respuesta al estrés y la esperanza de vida.
- Dirigirse a p66shc puede ofrecer una nueva estrategia para modular el envejecimiento y la resistencia al estrés en los mamíferos.
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