期刊
NEUROSCIENCE
卷 151, 期 3, 页码 771-779出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2007.10.057
关键词
ATF3; JNK; c-Jun; apoptosis; cerebellar granule neurons
Cerebellar granule neurons (CGNs) depend on potassium depolarization for survival and undergo apoptosis when deprived of depolarizing concentration of potassium. Activating transcription factor 3 (ATF3), a stress-inducible protein, belongs to the ATF/CREB family of transcription factors family and is involved in cell growth and apoptosis. However, the role of ATF3 in neuronal apoptosis remains unknown. Here, we showed that ATF3 was up-regulated under potassium deprivation in CGNs, and this induction was preceded by a rapid and sustained activation of c-Jun NH2-terminal kinase/c-Jun signaling pathway, which plays a fundamental role in neuronal apoptosis. Furthermore, ATF3 upregulation was abolished by inhibition of JNK or knockdown of c-Jun. Finally, knockdown of ATF3 by RNA interference protected CGNs from potassium deprivation-induced apoptosis. Taken together, our results indicate that ATF3 is a downstream target of JNK/c-Jun pathway and contributes to apoptosis induced by potassium deprivation in rat CGNs. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
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