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El precondicionamiento isquémico reduce la apoptosis mediante la regulación al alza del gen anti-muerte Bcl-2
N Maulik1, R M Engelman, J A Rousou
1Department of Surgery, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA. nmaulik@panda.uchc.edu
Circulation
|November 24, 1999
Resumen
El precondicionamiento isquémico protege el corazón mediante la activación de NF-kappaB y la regulación al alza de Bcl-2, que involucra especies reactivas de oxígeno. Este proceso reduce la apoptosis de los cardiomiocitos y el infarto de miocardio.
Área de la Ciencia:
- Investigaciones Cardiovasculares Investigación Cardiovascular Investigaciones Cardiovasculares
- Cardiología Molecular Cardiología Molecular
- La señalización celular.
Sus antecedentes:
- La lesión por reperfusión isquémica causa apoptosis de los cardiomiocitos y desregulación del gen Bcl-2.
- El precondicionamiento isquémico (PC) reduce la apoptosis a través de la tirosina quinasa, la p38 MAP quinasa y la señalización NF-kappaB.
- Las especies reactivas de oxígeno (ROS) están implicadas debido a la sensibilidad de NF-kappaB y el papel antioxidante de Bcl-2.
Objetivo del estudio:
- Investigar el papel de las especies reactivas de oxígeno y NF-kappaB en la vía de señalización protectora del precondicionamiento isquémico.
- Para determinar si ROS y NF-kappaB median la reducción de la apoptosis de los cardiomiocitos y el infarto de miocardio por PC.
Principales métodos:
- Los corazones aislados de ratas se sometieron a isquemia/reperfusión con o sin depurador de radicales hidroxilo (DMTU) o bloqueador de NF-kappaB (SN50).
- El precondicionamiento implicó repetidos episodios cortos de isquemia / reperfusión antes de la isquemia global sostenida y la reperfusión.
- Evaluación de la liberación de creatina quinasa, malonaldehído, tamaño del infarto, apoptosis, fragmentación del ADN, activación de NF-kappaB y expresión de Bcl-2.
Principales resultados:
- La PC redujo significativamente el infarto de miocardio y la apoptosis de los cardiomiocitos.
- Los efectos cardioprotectores de la PC fueron abolidos por DMTU y SN50.
- El PC aumentó la regulación de Bcl-2, un efecto parcialmente bloqueado por DMTU y SN50.
- Tanto la isquemia / reperfusión como la PC activaron NF-kappaB, con mayor actividad en los corazones de PC; DMTU y SN50 bloquearon esta activación.
Conclusiones:
- Las especies reactivas de oxígeno son cruciales para la transducción de señales mediada por PC que involucra a NF-kappaB.
- La activación de NF-kappaB por PC es mayor que en la isquemia/reperfusión simple, lo que se correlaciona con la reducción de la apoptosis.
- La upregulación del gen antioxidante Bcl-2 está inversamente relacionada con la reducción de la apoptosis de los cardiomiocitos lograda por PC.
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