S-nitrosilación de las metaloproteinasas de matriz: vía de señalización para la muerte celular neuronal
Zezong Gu1, Marcus Kaul, Boxu Yan
1Center for Neuroscience and Aging, Program in Cell Adhesion and Extracellular Matrix Biology, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science (New York, N.Y.)
|August 17, 2002
Resumen
La activación de las metaloproteinasas matriciales (MMP), crucial en la neurodegeneración y el accidente cerebrovascular, implica la S-nitrosilación. Este proceso activa el MMP-9, lo que lleva a la apoptosis neuronal a través de una nueva vía de proteólisis extracelular.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- La bioquímica es la bioquímica.
- Patología Patología Patología.
Sus antecedentes:
- Las metaloproteinasas matriciales (MMP) juegan un papel en las enfermedades neurodegenerativas y el accidente cerebrovascular.
- El mecanismo preciso de activación de MMP en estas condiciones no se entiende completamente.
Objetivo del estudio:
- Para aclarar el mecanismo de activación de MMP en el contexto de los trastornos neurológicos.
- Para investigar el papel de la S-nitrosilación en la activación de MMP y la muerte celular neuronal.
Principales métodos:
- Estudios in vivo de la isquemia cerebral.
- Experimentos in vitro para evaluar la activación del MMP-9.
- Espectrometría de masas para la identificación de los derivados del MMP-9.
- Análisis de la apoptosis neuronal.
Principales resultados:
- Se descubrió que el MMP-9 se colocaliza con la neuronal de óxido nítrico sintasa durante la isquemia cerebral.
- Se demostró que la S-nitrosilación activa el MMP-9 in vitro, induciendo la apoptosis neuronal.
- La espectrometría de masas identificó un derivado de ácido sulfínico o sulfónico estable de MMP-9, formado a través de la S-nitrosilación, en muestras in vitro e in vivo.
Conclusiones:
- La S-nitrosilación es un mecanismo clave para activar las MMP, incluida la MMP-9.
- Esta vía de activación contribuye a la muerte celular neuronal en condiciones como el accidente cerebrovascular.
- La oxidación de los MMP S-nitrolizados conduce a modificaciones post-traducionales estables y patológicamente activas.
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