Wang Xiaohui, Wang Zhuyao, Yao Yuzhen, Li Jingjin, Zhang Xiaojin, Li Chuanfu, Cheng Yunlin, Ding Guoxian, Liu Li, Ding Zhengnian
Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Biochim Biophys Acta. 2011 May;1813(5):827-38. doi: 10.1016/j.bbamcr.2011.01.027. Epub 2011 Feb 2.
Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. Alpha-lipoic acid (LA) has been used as a therapeutic approach for a variety of neural disorders. We recently reported that LA prevents local anesthetics-induced neurite loss. In this study, we hypothesized that LA administration promotes neurite outgrowth.
To test our hypothesis, we treated mouse neuroblastoma N2a cells and primary neurons with LA. Neurite outgrowth was evaluated by examination of morphological changes and by immunocytochemistry for β-tubulin-3. ROS production was examined, as were the phosphorylation levels of ERK and Akt. In separate experiments, we determined the effects of the inhibition of ERK or PI3K/Akt as well as ROS production on LA-induced neurite outgrowth.
LA promoted significantly neurite outgrowth in a time- and concentration-dependent manner. LA stimulation significantly increased the phosphorylation levels of both Akt and ERK and transiently induced ROS production. PI3K/Akt inhibition did not affect LA-induced neurite outgrowth. However, the inhibition of ERK activation completely abolished LA-induced neurite outgrowth. Importantly, the prevention of ROS production by antioxidants attenuated LA-stimulated ERK activation and completely abolished LA-promoted neurite outgrowth.
Our data suggest that LA stimulates neurite outgrowth through the activation of ERK signaling, an effect mediated through a ROS-dependent mechanism. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
神经突生长是神经元可塑性及神经元损伤后再生的一个重要方面。α-硫辛酸（LA）已被用作治疗多种神经疾病的一种方法。我们最近报道LA可预防局部麻醉药诱导的神经突丢失。在本研究中，我们假设给予LA可促进神经突生长。
为验证我们的假设，我们用LA处理小鼠神经母细胞瘤N2a细胞和原代神经元。通过检查形态变化及对β-微管蛋白-3进行免疫细胞化学来评估神经突生长。检测了活性氧（ROS）的产生以及细胞外信号调节激酶（ERK）和蛋白激酶B（Akt）的磷酸化水平。在单独的实验中，我们确定了抑制ERK或磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）以及ROS产生对LA诱导的神经突生长的影响。
LA以时间和浓度依赖性方式显著促进神经突生长。LA刺激显著增加了Akt和ERK的磷酸化水平，并短暂诱导了ROS的产生。抑制PI3K/Akt并不影响LA诱导的神经突生长。然而，抑制ERK激活完全消除了LA诱导的神经突生长。重要的是，抗氧化剂阻止ROS产生减弱了LA刺激的ERK激活，并完全消除了LA促进的神经突生长。
我们的数据表明，LA通过激活ERK信号通路刺激神经突生长，这一效应是通过ROS依赖性机制介导的。本文是名为“第11届欧洲钙研讨会”的特刊的一部分。
