RESUMEN
Heme oxygenase (HO-1), which may be induced by Cobaltic protoporphyrin IX chloride (CoPPIX) or Rosiglitazone (Ros), is a neuroprotective agent that effectively reduces ischemic stroke. Previous studies have shown that the neuroprotective mechanisms of HO-1 are related to JNK signaling. The expression of HO-1 protects cells from death through the JNK signaling pathway. This study aimed to ascertain whether the neuroprotective effect of HO-1 depends on the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and further influences the JNK signal transmission through HO-1. Prior to the ischemia-reperfusion experiment, CoPPIX was injected through the lateral ventricle for 5 consecutive days or Ros was administered via intraperitoneal administration in the week prior to transient ischemia. Our results demonstrated that HO-1 could inhibit the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and could ultimately diminish the phosphorylation of JNK3. Furthermore, the inhibition of JNK3 phosphorylation downregulated the level of p-c-Jun and elevated neuronal cell death in the CA1 of the hippocampus. Taken together, these findings suggested that HO-1 could ameliorate brain injury by regulating the MLK3-MKK7-JNK3 signaling module, which was scaffolded by JIP1 and JNK signaling during cerebral ischemia/reperfusion.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Isquemia Encefálica/enzimología , Hemo Oxigenasa (Desciclizante)/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Proteína Quinasa 10 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Animales , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/patología , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/enzimología , Región CA1 Hipocampal/patología , Muerte Celular/fisiología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Neuronas/efectos de los fármacos , Neuronas/enzimología , Neuronas/patología , Neuroprotección/efectos de los fármacos , Neuroprotección/fisiología , Fármacos Neuroprotectores/farmacología , Fosforilación , Proteínas Proto-Oncogénicas c-jun/metabolismo , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Rosiglitazona/farmacología , Proteina Quinasa Quinasa Quinasa 11 Activada por MitógenoRESUMEN
OBJECTIVE: To explore the effect of ginkgo biloba extract (EGb) as an adjunctive treatment of elderly patients with depression and the effect on the expression of serum S100B. METHODS: 136 elderly patients with depression were divided into EGbâ+â citalopram (Cit) group and Cit group equally. Efficacy was evaluated by Hamilton Depression Rating Scale (HAMD). Wisconsin Card Classification Test (WCST) was used to evaluate cognitive function. Serum S100B expression was measured with ELISA. The relationship of S100B with HAMD, Hamilton Anxiety Scale (HAMA) score, and WCST results was evaluated subsequently. RESULTS: The time of onset of efficacy was significantly shorter in EGbâ+âCit group. There were significant differences in HAMD and HAMA scores after treatment than before treatment between groups (all Pâ<â.05). After treatment, total number of WCST test, the number of continuous errors and non-persistent errors in both groups were less than those before treatment. The correct number and classifications number were increased than before treatment. In EGbâ+âCit group, correct numbers and classifications were increased, and the number of persistent errors was decreased. After treatment, S100B level was decreased, and S100B levels change in EGbâ+âCit group was greater than in Cit group. Serum S100B level was positively correlated with HAMD and HAMA scores before treatment and positively correlated with persistent errors number in WCST. CONCLUSION: EGb, as an adjunctive treatment, can effectively improve depressive symptoms and reduce expression of serum S100B, which is a marker of brain injury, suggesting that EGb restores neurologic function during the treatment of depression in elderly patients and S100B participates in the therapeutic mechanism. EGb combined with depressive drugs plays synergistic role, and the time of onset of efficacy is faster than single antidepressants.