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La expresión génica del canal K ((ATP) es inducida por la urocortina y media su efecto cardioprotector
K M Lawrence1, A Chanalaris, T Scarabelli
1Medical Molecular Biology Unit, Institute of Child Health, University College London, London, England.
Circulation
|September 18, 2002
Resumen
La urocortina, un agente cardioprotector, mejora la expresión de los canales de potasio Kir 6.1 en las células del corazón. Esta actividad específica del canal es crucial para la urocortina.
Área de la Ciencia:
- Cardiología Cardiología.
- Biología Molecular Biología Molecular
- Farmacología Farmacología.
Sus antecedentes:
- La urocortina es un nuevo agente cardioprotector.
- Protege los miocitos cardíacos de las lesiones por isquemia/reperfusión.
- La urocortina es eficaz cuando se administra en la reperfusión.
Objetivo del estudio:
- Para investigar los mecanismos moleculares subyacentes a los efectos cardioprotectores de la urocortina.
- Para identificar cambios específicos en la expresión génica inducidos por la urocortina.
- Determinar el papel de los objetivos identificados en la acción protectora de la urocortina.
Principales métodos:
- Análisis global de la expresión génica utilizando tecnología de chip genético en miocitos cardíacos.
- El tratamiento con urocortina.
- Evaluación de los efectos cardioprotectores en células cardíacas aisladas y corazones intactos.
- Bloqueo farmacológico de los canales K (((ATP) (generalizado y específico para las mitocondrias).
- Inhibición de la subunidad del canal Kir 6.1.
Principales resultados:
- La urocortina induce específicamente una mayor expresión de la subunidad del canal de potasio cardíaco Kir 6.1.
- La cardioprotección por la urocortina es bloqueada por los bloqueadores de los canales K ((ATP).
- El efecto cardioprotector de la cardiotropina-1 no se ve afectado por estos bloqueadores.
- La inhibición de Kir 6.1 mejora la muerte celular cardíaca después de la isquemia.
Conclusiones:
- Este estudio informa la primera instancia de expresión alterada de subunidades del canal K (((ATP) por un agente cardioprotector.
- La apertura del canal K ((ATP) es esencial para el efecto cardioprotector de la urocortina.
- Kir 6.1 es un mediador clave de la cardioprotección inducida por la urocortina.
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