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La asociación endotélica de la sintetasa de óxido nítrico mediada por estradiol con la proteína de choque térmico 90
Eberhard Schulz1, Elad Anter, Ming-Hui Zou
1Evans Memorial Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass 02118, USA.
Circulation
|June 22, 2005
Resumen
El estradiol activa la proteína quinasa activada por AMP (AMPK) en las células endoteliales, que es esencial para la activación de la óxido nítrico sintasa (eNOS). Esta vía implica la proteína de choque térmico 90 (HSP90) y tiene un impacto en la bioactividad del NO.
Área de la Ciencia:
- Endocrinología Endocrinología.
- Biología Molecular Biología Molecular
- Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular
Sus antecedentes:
- El estradiol activa la endotélica óxido nítrico sintasa (eNOS) a través de varias vías de señalización.
- La proteína quinasa activada por AMP (AMPK) es crucial para la adaptación celular y se ha relacionado con la activación de eNOS por otras hormonas.
Objetivo del estudio:
- Para investigar si el estradiol activa la AMPK en las células endoteliales.
- Para determinar el papel de la AMPK en la activación de eNOS inducida por el estradiol.
Principales métodos:
- Las células endoteliales de la aorta porcina fueron tratadas con estradiol.
- La activación de la AMPK se evaluó mediante la fosforilación de la AMPK y la acetil-CoA carboxilasa.
- Se empleó la expresión mediada por adenovirus de AMPK dominante-negativo y estudios en ratones alfa1-AMPK-nulo.
Principales resultados:
- AMPK activado dependiendo del tiempo y la concentración de estradiol, independiente de los niveles de AMP y ERalpha, pero que requiere metabolitos de estradiol.
- El estradiol aumentó la actividad catalítica de eNOS, un efecto revertido por la AMPK dominante-negativa.
- La inhibición de AMPK disminuyó la interacción de eNOS con HSP90 y la producción de NO inducida por estradiol en los vasos sanguíneos de ratones.
Conclusiones:
- La activación de AMPK es esencial para la activación de eNOS inducida por el estradiol.
- AMPK promueve la interacción de eNOS con HSP90, modulando la bioactividad NO de las células endoteliales.
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