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Strategies for Study of Neuroprotection from Cold-preconditioning
Published on: September 3, 2010
La neuroprotección mediada por la eritropoietina implica el diálogo cruzado entre las cascadas de señalización Jak2 y
1Center for Neuroscience and Aging Research, The Burnham Institute, La Jolla, CA 92037, USA.
Nature
|August 9, 2001
Resumen
El precondicionamiento de la eritropoietina (EPO) protege las células cerebrales del daño mediante la activación de los receptores neuronales de EPO. Esto desencadena una nueva vía de señalización que involucra a Janus kinase-2 (Jak2) y el factor nuclear-kappaB (NF-kappaB), previniendo la muerte de las neuronas.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La señalización celular.
Sus antecedentes:
- La eritropoietina (EPO), conocida principalmente por regular la producción de células sanguíneas, también se encuentra en el cerebro.
- El factor inducible a la hipoxia-1 (HIF-1) aumenta la producción de EPO bajo condiciones hipóxicas.
- El estrés oxidativo y nitrosativo puede inducir la producción de EPO en el cerebro.
Objetivo del estudio:
- Investigar los efectos neuroprotectores del precondicionamiento con EPO en modelos de daño neuronal.
- Para aclarar los mecanismos moleculares subyacentes a la neuroprotección mediada por EPO.
- Para determinar si la EPO activa una nueva vía de señalización en las neuronas.
Principales métodos:
- Modelos utilizados de daño neuronal isquémico y excitotóxico.
- Examinó el papel de los receptores de EPO (EPOR) en la supervivencia neuronal.
- Se han investigado vías de señalización que incluyen Janus kinase-2 (Jak2) y factor nuclear-kappaB (NF-kappaB).
- Técnicas de transfección empleadas con interferencia dominante Jak2 y superrepresor IkappaBalpha.
Principales resultados:
- EPO precondiciona las neuronas protegidas contra la apoptosis inducida por el NMDA y el óxido nítrico (NO).
- La activación de las EPOR neuronales inició el diálogo cruzado entre las vías de señalización Jak2 y NF-kappaB.
- La activación de Jak2 mediada por EPOR condujo a la translocación nuclear de NF-kappaB y a la transcripción de genes neuroprotectores.
- El bloqueo de la señalización Jak2 o NF-kappaB abrogó los efectos neuroprotectores de la EPO.
Conclusiones:
- Las EPOR neuronales activan una vía neuroprotectora distinta que involucra a Jak2 y NF-kappaB.
- Esta vía mediada por EPO previene la apoptosis inducida por las excitotoxinas y los radicales libres.
- Los hallazgos sugieren un mecanismo potencial de neuroprotección observado en el precondicionamiento hipóxico-isquémico.
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