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dc.contributor.authorChen, C. H.zh_CN
dc.contributor.authorZheng, B.zh_CN
dc.contributor.authorHan, J. H.zh_CN
dc.contributor.authorLin, S. C.zh_CN
dc.contributor.author林圣彩zh_CN
dc.date.accessioned2013-12-12T02:24:14Z
dc.date.available2013-12-12T02:24:14Z
dc.date.issued1997zh_CN
dc.identifier.citationJournal of Biological Chemistry,272(13):8679-8685zh_CN
dc.identifier.issn0021-9258zh_CN
dc.identifier.otherWOS:A1997WQ63500083zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/65316
dc.description.abstractThe stress-activated protein kinases c-Jun-activated kinase (JNK) and p38 are implicated in neuronal apoptosis. Early studies in cell lines suggested a requirement for both in the apoptosis induced by withdrawal of nerve growth factor. However, studies in neuronal cells typically implicate JNK but not p38 in apoptosis. In some cases, p38 is implicated, but the role of JNK is undefined. It remains unclear whether p38 and JNK have differing roles dependent on cell type, apoptotic stimulus, or mechanism of cell death or whether they are redundant and each sufficient to induce identical forms of cell death. We investigate the relative roles of these protein kinases in different death mechanisms in a single system, cultured cerebellar granule neurons. Apoptosis induced by withdrawal of trophic support and glutamate are mechanistically different in terms of caspase activation, DNA fragmentation profile, chromatin morphology, and dependence on de novo gene expression. Caspase-independent apoptosis induced by glutamate is accompanied by strong activation of p38, and dominant negatives and inhibitors of the p38 pathway prevent this apoptosis. In contrast, withdrawal of trophic support induces caspase-dependent death accompanied by JNK-dependent phosphorylation of c-Jun, and inhibition of JNK is sufficient to prevent the death induced by withdrawal of trophic support. Inhibition of p38 does not block withdrawal of trophic support-induced death, nor does inhibition of JNK block glutamate-induced death. We propose that mechanistically different forms of apoptosis have differing requirements for p38 and JNK activities in neurons and demonstrate that only inhibition of the appropriate kinase will prevent neurons from undergoing apoptosis.zh_CN
dc.language.isoen_USzh_CN
dc.subjectCEREBELLAR GRANULE NEURONSzh_CN
dc.subjectDNA LOOP DOMAINSzh_CN
dc.subjectCELL-DEATHzh_CN
dc.subjectSYMPATHETIC NEURONSzh_CN
dc.subjectCASPASE ACTIVATIONzh_CN
dc.subjectMOUSE HIPPOCAMPUSzh_CN
dc.subjectCEREBRAL-ISCHEMIAzh_CN
dc.subjectP38zh_CN
dc.subjectJNKzh_CN
dc.subjectINHIBITIONzh_CN
dc.titleCharacterization of a novel mammalian RGS protein that binds to G alpha proteins and inhibits pheromone signaling in yeastzh_CN
dc.typeArticlezh_CN


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