RESUMO
Although kainate receptors play important roles in ischemic stroke, the molecular mechanisms underlying postischemic regulation of kainate receptors remain unclear. In this study we demonstrate that Src family kinases contribute to the potentiation of kainate receptor function. Brain ischemia and reperfusion induce rapid and sustained phosphorylation of the kainate receptor subunit GluK2 by Src in the rat hippocampus, implicating a critical role for Src-mediated GluK2 phosphorylation in ischemic brain injury. The NMDA and kainate receptors are involved in the tyrosine phosphorylation of GluK2. GluK2 binds to Src, and the tyrosine residue at position 590 (Y590) on GluK2 is a major site of phosphorylation by Src kinases. GluK2 phosphorylation at Y590 is responsible for increases in whole-cell currents and calcium influx in response to transient kainate stimulation. In addition, GluK2 phosphorylation at Y590 facilitates the endocytosis of GluK2 subunits, and the activation of JNK3 and its substrate c-Jun after long-term kainate treatment. Thus, Src phosphorylation of GluK2 plays an important role in the opening of kainate receptor channels and downstream proapoptosis signaling after brain ischemia. The present study reveals an additional mechanism for the regulation of GluK2-containing kainate receptors by Src family kinases, which may be of pathological significance in ischemic stroke.
Assuntos
Isquemia Encefálica/metabolismo , Hipocampo/metabolismo , Receptores de Ácido Caínico/metabolismo , Transdução de Sinais/fisiologia , Acidente Vascular Cerebral/metabolismo , Regulação para Cima/fisiologia , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Células HEK293 , Hipocampo/patologia , Humanos , Masculino , Proteína Quinase 10 Ativada por Mitógeno/genética , Proteína Quinase 10 Ativada por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Ácido Caínico/genética , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia , Tirosina/genética , Tirosina/metabolismo , Quinases da Família src/genética , Quinases da Família src/metabolismo , Receptor de GluK2 CainatoRESUMO
AIM: To synthetically analyze and probe into the diagnosis of H pylori infection, we followed the principles of evidence-based medicine. METHODS: A total of 22 papers of prevalence survey and case-control studies were selected for studying about diadynamic methods. Using meta-analysis, we analyzed the different diadynamic methods of H pylori in China. RESULTS: Through meta-analysis, among the five diadynamic methods, the accuracy of polymerase chain reaction (PCR) was the highest (98.47%) and PCR was the most sensitive method (Sp: 99.03%). CONCLUSION: Among the five diadynamic methods, the accuracy of PCR is the highest and PCR is the most sensitive method to diagnose the infection of H pylori.
