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Un péptido codificado por una transcripción anotada como ARN largo no codificante mejora la actividad de SERCA en el
Benjamin R Nelson1, Catherine A Makarewich1, Douglas M Anderson1
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science (New York, N.Y.)
|January 28, 2016
Resumen
Los investigadores descubrieron un péptido específico para el músculo, el marco de lectura enano abierto (DWORF), que mejora la contracción muscular al aumentar la actividad de la bomba SERCA. DWORF mejora el manejo del calcio y la función muscular en ratones.
Área de la Ciencia:
- Biología molecular
- Fisiología muscular
Sus antecedentes:
- La contracción muscular se basa en el ciclo del calcio (Ca2+).
- El retículo sarcoplásmico (SR) y la bomba de Ca2+-ATPasa (SERCA) son cruciales para la recaptación de Ca2+.
Objetivo del estudio:
- Identificar nuevos reguladores de la actividad del SERCA.
- Para investigar la función de un nuevo péptido muscular específico, DWORF.
Principales métodos:
- Identificó un ARN largo no codificante específico del músculo que codifica el péptido DWORF.
- DWORF localizado en la membrana SR.
- Se estudió la función DWORF en cardiomiocitos de ratón y músculo esquelético lento.
Principales resultados:
- DWORF mejora la actividad de SERCA desplazando inhibidores como el fosfolambano.
- La sobreexpresión de DWORF en los cardiomiocitos aumentó la amplitud transitorio de Ca2+ y la carga de Ca2+ SR.
- La deficiencia de DWORF en el músculo esquelético condujo a un menor aclaramiento y relajación de Ca2+.
Conclusiones:
- DWORF es el primer péptido endógeno conocido que interactúa físicamente y activa SERCA.
- DWORF representa un nuevo mecanismo para mejorar la contractilidad muscular y el manejo del calcio.
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