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El control circadiano de la vía de rescate de NAD+ por CLOCK-SIRT1
Yasukazu Nakahata1, Saurabh Sahar, Giuseppe Astarita
1Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Science (New York, N.Y.)
|March 17, 2009
Resumen
El reloj circadiano regula los niveles intracelulares de NAD+ controlando la expresión de la enzima NAMPT. Esto crea un bucle de retroalimentación entre el metabolismo celular y los ritmos circadianos.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Cronobiología cronobiología.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Los ritmos circadianos regulan numerosos procesos fisiológicos.
- El regulador circadiano central CLOCK es una histona acetiltransferasa.
- SIRT1, una histona desacetilasa dependiente de NAD+, contrapone la actividad de CLOCK.
Objetivo del estudio:
- Para investigar la regulación circadiana de los niveles intracelulares de NAD+.
- Para aclarar el papel de NAMPT en la expresión génica circadiana.
- Para revelar la interacción entre el metabolismo celular y los ritmos circadianos.
Principales métodos:
- Análisis de las oscilaciones circadianas en los niveles de NAD+.
- Investigando la regulación CLOCK:BMAL1 de la expresión NAMPT.
- Utilizando el inhibidor de NAMPT FK866 para evaluar su impacto en la expresión génica circadiana.
Principales resultados:
- Los niveles intracelulares de NAD+ exhiben un ritmo de 24 horas impulsado por el reloj circadiano.
- CLOCK:BMAL1 regula directamente la expresión circadiana de NAMPT.
- NAMPT es esencial para modular la expresión génica circadiana.
Conclusiones:
- Existe un circuito de retroalimentación transcripcional-enzimática entrelazado entre el metabolismo celular y los ritmos circadianos.
- SIRT1 juega un papel en la síntesis circadiana de NAD+.
- La actividad de NAMPT es crucial para mantener el ritmo circadiano.
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