期刊
NEUROSCIENCE LETTERS
卷 434, 期 1, 页码 6-11出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2008.01.057
关键词
DRG; neurotrophic factors; axon regeneration; akt; cell culture; axotomy
Hexokinase is known as the first enzyme and rate-limiting step in glycolysis. The role of hexokinase activity and localization in regulating the rate of axonal regeneration was studied in cultured adult sensory neurons of dorsal root ganglia (DRG). Immunofluorescent staining of DRG demonstrated that small-medium neurons and satellite cells exhibited high levels of expression of hexokinase I. Large neurons had negative staining for hexokinase I. Intracellular localization and biochemical studies in cultured adult rat sensory neurons revealed that hexokinase I was almost exclusively found in the mitochondrial compartment. The hypothesis that neurotrophic factor dependent activation of Akt would regulate hexokinase association with the mitochondria was tested and quantitative Western blotting showed no effect of blockade of the phosphoinositide 3-kinase (PI3-kinase)/Akt pathway using the inhibitor LY294002, indicating this interaction of hexokinase with mitochondria was not neurotrophic factor or Akt-dependent. Finally, pharmacological blockade of hexokinase activity and inhibition of localization to the mitochondrial compartment with hexokinase II VDAC binding domain (Hxk2VBD) peptide caused a significant inhibition of neurotrophic factor-directed axon outgrowth. The results support a key role for hexokinase activity and/or localization to the mitochondria in the regulation of neurite outgrowth in cultured adult sensory neurons. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据