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El nNOS localizado por sarcolema es necesario para mantener la actividad después de un ejercicio leve
Yvonne M Kobayashi1, Erik P Rader, Robert W Crawford
1Howard Hughes Medical Institute, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, Iowa 52242-1101, USA.
Nature
|October 28, 2008
Resumen
La fatiga excesiva por el ejercicio en condiciones neuromusculares puede deberse a la reducción de la señalización por la sintasa neuronal de óxido nítrico (nNOS) localizada en el sarcolema. La restauración de esta vía de señalización podría mejorar la capacidad de ejercicio y reducir la discapacidad en pacientes afectados.
Área de la Ciencia:
- Fisiología muscular La fisiología muscular.
- Trastornos neuromusculares Trastornos neuromusculares Trastornos neuromusculares Trastornos neuromusculares Trastornos neuromusculares Trastornos neuromusculares Trastornos neuromusculares Trastornos neuromusculares Trastornos neuromusculares Trastornos neuromusculares
- La señalización del óxido nítrico.
Sus antecedentes:
- Muchas afecciones neuromusculares causan una fatiga desproporcionada inducida por el ejercicio.
- Los mecanismos subyacentes de esta fatiga a menudo son desconocidos e intratables.
- Esta fatiga contribuye significativamente a la discapacidad en las personas afectadas.
Objetivo del estudio:
- Investigar el mecanismo detrás de la fatiga inducida por el ejercicio exagerado en los trastornos neuromusculares.
- Identificar el papel de la sintasa neuronal de óxido nítrico (nNOS) localizada en el sarcolema en la actividad muscular.
- Explorar posibles objetivos terapéuticos para mejorar la capacidad de ejercicio.
Principales métodos:
- Se utilizaron modelos de ratón para estudiar las respuestas a la fatiga inducida por el ejercicio.
- Se examinaron ratones sin nNOS y modelos con mala localización de nNOS.
- Analizaron la patología muscular, la producción de fuerza y las vías de señalización.
- Biopsias musculares de pacientes investigados para la expresión de nNOS.
Principales resultados:
- Los ratones nNOS-null exhibieron fatiga exagerada sin patología muscular ni pérdida de fuerza.
- La mala localización de nNOS condujo a una inactividad prolongada, mejorada por la mejora de la GMPc.
- Se observó una disminución de la tinción nNOS sarcolemal en las biopsias de miopatía de los pacientes.
- La falta de señalización inducida por la contracción de nNOS afecta la vasodilatación en los músculos activos.
Conclusiones:
- La fatiga excesiva está relacionada con una deterioración de la señalización de la nNOS localizada en el sarcolema.
- La reducción de la señalización nNOS afecta a la vasodilatación mediada por cGMP en los músculos activos.
- Las estrategias terapéuticas dirigidas a la señalización nNOS pueden mejorar la fatiga inducida por el ejercicio en miopatías.
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