High-mobility group box 1 induces neuron autophagy in a rat spinal root avulsion model
High-mobility group box 1 induces neuron autophagy in a rat spinal root avulsion model
复制标题
高迁移率组盒 1 在大鼠脊髓根撕脱模型中诱导神经元自噬
DOI：
10.1016/j.neuroscience.2015.12.020
复制
发表时间：
2016-02
期刊：
影响因子：
3.3
通讯作者：
Chen A.
中科院分区：
文献类型：
--
作者：
Zhu L.;Huang G.;Sheng J.;Fu Q.;Chen A.
自噬是一种受到严格调控的溶酶体依赖性分解代谢途径，参与神经系统的多种病理状态。高迁移率族蛋白1（HMGB 1）是一种炎症介质，已知从受损细胞释放到局部微环境中。然而，自噬是否被诱导以及外源性HMGB 1是否参与了脊神经根撕脱的过程仍不清楚。在这里，我们研究了自噬的诱导作用和HMGB 1在脊神经根撕脱过程中的可能作用。结果发现，自噬在脊髓前角被激活，表现为自噬标志物微管相关蛋白轻链3-II（LC 3-II）的表达增加，多价螯合体1（p62）的降解和自噬体的形成，并且在大鼠脊髓根撕脱模型中腹膜内注射抗HMGB 1中和抗体后，自噬被抑制。此外，HMGB 1诱导的自噬和激活的有丝分裂原活化蛋白激酶（MAPK）在原代脊髓神经元，包括c-Jun N-末端激酶（JNK），细胞外信号调节激酶（ERK），和p38 MAPK。抑制JNK或ERK活性可显著阻断HMGB 1诱导的原代脊髓神经元自噬作用。最后，HMGB 1诱导的自噬增加了原代脊髓神经元在氧-葡萄糖剥夺条件下的细胞活力。上述结果提示HMGB 1是自噬的重要调节因子，HMGB 1诱导的自噬在保护脊髓神经元免受损伤中起重要作用，这可能为研究脊神经根性撕脱伤的病理生理过程提供新的思路。
Autophagy, a tightly regulated lysosome-dependent catabolic pathway, is implicated in various pathological states in the nervous system. High-mobility group box 1 (HMGB1) is an inflammatory mediator known to be released into the local microenvironment from damaged cells. However, whether autophagy is induced and exogenous HMGB1 is involved in the process of spinal root avulsion remain unclear. Here, we investigated the induction effect of autophagy and the possible role of HMGB1 during spinal root avulsion. It was found that autophagy was activated in the anterior horn of the spinal cord as represented by the increased expression of the autophagic marker microtubule-associated protein light chain 3-II (LC3-II), degradation of sequestosome 1 (p62), and formation of autophagosomes, and that autophagy was inhibited after intraperitoneal injection of anti-HMGB1-neutralizing antibodies in the rat spinal root avulsion model. In addition, HMGB1-induced autophagy and activated mitogen-activated protein kinases (MAPKs) in primary spinal neurons, including c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK), and p38MAPK. Inhibition of JNK or ERK activity significantly blocked the effect of HMGB1-induced autophagy in primary spinal neurons. Finally, HMGB1-induced autophagy increased cell viability in primary spinal neurons under oxygen-glucose deprivation conditions. The above results suggest that HMGB1 is a critical regulator of autophagy and HMGB1-induced autophagy plays an important role in protecting spinal neurons against injury, which may provide new insights into the pathophysiological process of spinal root avulsion.
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影响因子：
3
作者：
Kanno, Haruo;Ozawa, Hiroshi;Itoi, Eiji
通讯作者：
Itoi, Eiji
DOI：
10.1016/j.biocel.2004.05.009
发表时间：
2004-12
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Tanida I;Ueno T;Kominami E
通讯作者：
Kominami E
影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
4.3
作者：
Liang, Yue;Hou, Changchun;Chen, Yiqiang
通讯作者：
Chen, Yiqiang
影响因子：
6.1
作者：
Erlich, S.;Alexandrovich, A.;Pinkas-Kramarski, R.
通讯作者：
Pinkas-Kramarski, R.