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El sensor redox de cisteína en PKGIa permite la activación inducida por oxidantes
Joseph R Burgoyne1, Melanie Madhani, Friederike Cuello
1Department of Cardiology, Cardiovascular Division, King's College London, Rayne Institute, St. Thomas' Hospital, London SE1 7EH, UK.
Science (New York, N.Y.)
|August 25, 2007
Resumen
La proteína quinasa dependiente de la guanilil ciclasa (PKG) actúa como un sensor redox. La oxidación activa la PKG, aumentando la afinidad del sustrato y regulando la función celular independientemente del óxido nítrico y el cGMP.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología celular Biología celular.
- Fisiología Fisiología Fisiología.
Sus antecedentes:
- Los niveles de oxidantes celulares regulan la función celular a través de la señalización bioquímica.
- La proteína quinasa dependiente de la guanilil ciclasa (PKG) es una enzima de señalización clave.
- El óxido nítrico (NO) y el monofosfato cíclico de guanosina (cGMP) son activadores clásicos de la PKG.
Objetivo del estudio:
- Para investigar si PKG puede funcionar como un sensor redox directo.
- Para dilucidar el mecanismo molecular de la activación de PKG por los oxidantes.
- Para explorar la relevancia fisiológica de la activación de PKG mediada por oxidantes.
Principales métodos:
- Exposición de células y tejidos al peróxido de hidrógeno.
- Análisis de la formación de enlaces disulfuro de las interproteínas en PKGIalpha.
- Pruebas in vitro de quinasa para evaluar la actividad y la afinidad del sustrato.
- Estudios en células y tejidos de ratas.
Principales resultados:
- La isoforma PKGIalpha forma un enlace disulfuro interproteínico entre sus subunidades al exponerse al peróxido de hidrógeno.
- Esta oxidación activa directamente la actividad de la PKGIalpha kinase.
- La formación de disulfuro aumenta la afinidad de PKGIalpha por sus sustratos.
- La activación de PKG inducida por oxidantes ocurre independientemente de la vía NO/cGMP.
Conclusiones:
- PKG detecta directamente los oxidantes celulares, funcionando como un sensor redox.
- La activación de PKG inducida por oxidación proporciona un mecanismo de regulación independiente de la GMPc.
- Esta vía explica la vasorelaxación mediada por oxidantes y el papel del peróxido de hidrógeno como un factor hiperpolarizante derivado del endotelio.
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