Heme oxygenase-1 regulates the JNK signaling pathway through the MLK3-MKK7-JNK3 signaling module in brain ischemia injury.
Brain Res
; 1429: 1-8, 2012 Jan 06.
Article
en En
| MEDLINE
| ID: mdl-22088822
ABSTRACT
Although previous researches indicated that heme oxygenase-1 (HO-1) plays a conspicuous role in neuronal injury induced by reperfusion following the brain ischemia, reasonable mechanisms for the role of HO-1 are not clear. In this work, we investigated whether HO-1 was involved in the regulation of the c-Jun N-terminal kinase (JNK) signaling pathway and neuronal cell injury induced by the brain ischemia followed by reperfusion. Cobaltic protoporphyrin (CoPP), an activator of HO-1, was administrated to induce the overexpression of HO-1 by intracerebroventricular infusion 20 min before ischemia. The results showed that the combination of HO-1-mixed lineage kinase 3 (MLK3), MLK3-mitogen-activated kinase kinase 7 (MKK7) and MKK7-JNK3 increased to a peak at 6h of reperfusion following 15 min of ischemia induced by four-vessel occlusion in rats, and these effects were downregulated by CoPP. In addition, CoPP could inhibit the activation of JNK3, c-Jun and caspase-3. Furthermore, pretreatment with CoPP significantly increased the survival of neurons after 5 days of reperfusion. In contrast, all of the above effects of CoPP were reversed by zinc protoporphyrin (ZnPP), a selective inhibitor of HO-1. Our results suggested that HO-1 could protect neurons against brain ischemic injury by downregulating the JNK signaling pathway through the MLK3-MKK7-JNK3 signaling module.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión
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Isquemia Encefálica
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Sistema de Señalización de MAP Quinasas
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Hemo Oxigenasa (Desciclizante)
Límite:
Animals
Idioma:
En
Revista:
Brain Res
Año:
2012
Tipo del documento:
Article