Inhibition of c-Jun phosphorylation reduces axonal outgrowth of adult rat nodose ganglia and dorsal root ganglia sensory neurons
Inhibition of c-Jun phosphorylation reduces axonal outgrowth of adult rat nodose ganglia and dorsal root ganglia sensory neurons
复制标题
DOI：
10.1016/j.mcn.2004.07.001
复制
发表时间：
2004-11-01
影响因子：
3.5
通讯作者：
Kanje, M
中科院分区：
文献类型：
--
作者：
Lindwall, C;Dahlin, L;Kanje, M
c-Jun激活对感觉神经元存活和再生的作用尚不清楚。在这里，我们报告，c-Jun N-末端激酶（JNK）介导的c-Jun激活是重要的感觉神经元的轴突生长在大鼠结状和背根神经节（DRG）。迷走神经或坐骨神经的外周切断导致神经元核中激活的JNK（p-JNK）的大量和快速但短暂的增加，随后是c-Jun磷酸化和激活转录因子3（ATF 3）诱导。选择性JNK抑制剂SP 600125和（D）-JNKI 1抑制JNK不影响分离或分离神经节中的神经元存活，但显著减少轴突生长、c-Jun激活和ATF 3诱导。使用逆行标记，我们证明了激活的c-Jun（p-c-Jun）和ATF 3与再生神经元相关。总之，我们的研究结果表明，JNK介导的c-Jun激活是神经损伤的第一个细胞体反应之一，这种激活和随后的ATF 3诱导与轴突生长有关。(C)2004年爱思唯尔公司All rights reserved.
The role of c-Jun activation for survival and regeneration of sensory neurons is unclear. Here we report that c-Jun N-terminal kinase (JNK)-mediated c-Jun activation is important for axonal outgrowth of sensory neurons in rat nodose and dorsal root ganglia (DRG). Peripheral severance of the vagus or the sciatic nerve resulted in a massive and rapid, but transient increase of the activated JNK (p-JNK) in neuronal nuclei, followed by c-Jun phosphorylation and activating transcription factor-3 (ATF3) induction. JNK inhibition by the selective JNK inhibitors SP600125 and (D)-JNKI1 did not affect neuronal survival in explanted or dissociated ganglia, but dramatically reduced axonal outgrowth, c-Jun activation, and ATF3 induction. Using retrograde labeling, we demonstrated that activated c-Jun (p-c-Jun) and ATF3 were associated with regenerative neurons. Taken together, our results suggest that JNK-mediated c-Jun activation is one of the first cell body reactions in response to nerve injury and that this activation and subsequent ATF3 induction are associated with axonal outgrowth. (C) 2004 Elsevier Inc. All rights reserved.