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El regulador de información silenciosa 1 protege el corazón de la isquemia / reperfusión
Chiao-Po Hsu1, Peiyong Zhai, Takanobu Yamamoto
1Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, Newark, 07103, USA.
Circulation
|November 10, 2010
Resumen
El regulador de información silenciosa 1 (Sirt1) protege el corazón de la lesión por isquemia/reperfusión (I/R). La upregulación de Sirt1 reduce el daño cardíaco y el estrés oxidativo mediante la activación de genes protectores e inhibición de las vías de muerte celular.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- Cardiología Molecular Cardiología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- El regulador de información silenciosa 1 (Sirt1) es una histona desacetilasa conocida por retrasar el envejecimiento y proteger contra el estrés oxidativo.
- Se investigó su papel en la lesión de isquemia / reperfusión (I / R) del miocardio, una condición crítica en la enfermedad cardiovascular.
Objetivo del estudio:
- Para determinar si Sirt1 confiere protección contra la isquemia miocárdica / lesión de reperfusión (I / R).
- Para aclarar los mecanismos moleculares subyacentes a los efectos protectores potenciales de Sirt1 en el corazón.
Principales métodos:
- Se utilizaron modelos de ratón con knockout Sirt1 específico para el corazón y modelos de ratón con sobreexpresión transgénica.
- Evaluación del tamaño del infarto de miocardio, los marcadores de apoptosis (coloración TUNL) y la función cardíaca después de I/R.
- Expresión analizada de las moléculas claves pro-supervivencia y pro-apoptóticas.
- Investigó el papel del factor de transcripción FoxO1 en la protección mediada por Sirt1.
Principales resultados:
- La isquemia/reperfusión (I/R) redujo significativamente la expresión de Sirt1 en el corazón.
- Los ratones Sirt1 knockout mostraron un aumento en el tamaño del infarto (44% frente a 15%) en comparación con los controles.
- La sobreexpresión de Sirt1 redujo el tamaño del infarto (15% vs. 36%) y la apoptosis.
- Sirt1 mejoró la recuperación funcional cardíaca y las enzimas antioxidantes reguladas al alza (superóxido de manganeso dismutasa, tioredoxina-1) y Bcl-xL, mientras que regulaba a la baja Bax y la caspasa-3 escindida.
- La activación de Sirt1 de FoxO1 fue crucial para regular los antioxidantes y reducir el estrés oxidativo.
Conclusiones:
- Sirt1 demuestra un papel protector significativo contra la lesión I / R del miocardio.
- La protección está mediada por la regulación al alza de las defensas antioxidantes y la regulación a la baja de los factores pro-apoptóticos a través de la activación de FoxO1.
- La activación de Sirt1 conduce a una disminución del estrés oxidativo en los miocitos cardíacos durante los eventos I / R.
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