title: Essential role of ERK activation in neurite outgrowth induced by α-lipoic acid.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Zhuyao
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Yao
authors.forename: Jingjin
authors.initials: J
authors.lastname: Li
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.forename: Yunlin
authors.initials: Y
authors.lastname: Cheng
authors.forename: Guoxian
authors.initials: G
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Zhengnian
authors.initials: Z
authors.lastname: Ding
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D048049:Extracellular Signal-Regulated MAP Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D008063:Thioctic Acid