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La eliminación del factor de transcripción de la proteína-1 activada JunD induce estrés oxidativo y acelera la

Francesco Paneni¹, Elena Osto, Sarah Costantino

¹Cardiology and Cardiovascular Research, Institute of Physiology and University Hospital, Zürich, Switzerland.

|February 16, 2013

Resumen

El factor de transcripción JunD protege contra el envejecimiento vascular al mantener el equilibrio de las especies reactivas de oxígeno. La pérdida de JunD acelera el envejecimiento, mientras que su sobreexpresión previene la disfunción endotelial relacionada con la edad.

Área de la Ciencia:

Biología Vascular Biología Vascular
Investigación sobre el envejecimiento Investigación sobre el envejecimiento.
El estrés oxidativo es el estrés oxidativo.

Sus antecedentes:

Las especies reactivas de oxígeno (ROS) influyen significativamente en el envejecimiento vascular.
JunD, un factor de transcripción, es reconocido por su papel en la lucha contra el estrés oxidativo.
La función específica de JunD en la homeostasis vascular de ROS no se había determinado previamente.

Objetivo del estudio:

Para investigar el papel de JunD en el mantenimiento de la salud vascular durante el envejecimiento.
Aclarar los mecanismos por los cuales JunD influye en el equilibrio de las especies reactivas de oxígeno en la vasculatura.
Para determinar si JunD podría ser un objetivo terapéutico para la disfunción vascular relacionada con la edad.

Principales métodos:

Utilizó JunD knockout (JunD(-/-)) y ratones de tipo salvaje en varias edades.
Se evaluó la función endotelial, la producción de óxido nítrico y los marcadores de estrés oxidativo.
Se analizó la expresión de enzimas antioxidantes, subunidades de NADPH oxidasa y marcadores de senescencia.
Investigó la regulación de JunD en ratones envejecidos y células endoteliales humanas.

Principales resultados:

JunD(-/-) los ratones exhibieron un deterioro de la vasorelajación, una reducción de la biodisponibilidad del óxido nítrico y un aumento del estrés oxidativo.
El envejecimiento vascular en ratones de tipo salvaje se asoció con una disminución de la expresión y actividad de JunD.
La sobreexpresión de JunD protege contra la disfunción endotelial inducida por la edad.
JunD knockdown en las células humanas imitaba el desequilibrio oxidativo observado en el envejecimiento.

Conclusiones:

JunD juega un papel protector crítico contra la disfunción endotelial relacionada con el envejecimiento.
JunD es esencial para mantener la homeostasis de las especies reactivas de oxígeno en la vasculatura.
Dirigirse a JunD puede ofrecer una nueva estrategia para combatir el envejecimiento vascular impulsado por ROS.

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