Epoxyeicosatrienoic acids enhance axonal growth in primary sensory and cortical neuronal cell cultures.
Epoxyeicosatrienoic acids enhance axonal growth in primary sensory and cortical neuronal cell cultures.
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DOI：
10.1111/j.1471-4159.2010.07139.x
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发表时间：
2011-05
影响因子：
4.7
通讯作者：
Lein PJ
中科院分区：
文献类型：
--
作者：
Abdu E;Bruun DA;Yang D;Yang J;Inceoglu B;Hammock BD;Alkayed NJ;Lein PJ
最近有报道称，代谢环氧二碳三烯酸（EETs）的主要酶——可溶性环氧化物水解酶（sEH）在皮质神经元轴突中表达；然而，轴突sEH定位的功能相关性尚不清楚。免疫细胞化学分析表明，不仅在皮层，而且在交感和感觉神经元的原代培养中，sEH的主要轴突定位。培养感觉神经元的形态计量学分析表明，暴露于eet的区域异构体混合物（0.01至1.0μM）会导致轴突生长的浓度依赖性增加。这种轴突促进活性并不是所有eet区域异构体的普遍特性，因为暴露于14,15- eet的感觉神经元的轴突生长得到增强，而暴露于8,9或11,12- eet的感觉神经元的轴突生长没有增强。14,15- eet也促进培养皮层神经元轴突的生长。同时暴露于eet和两种结构不同的sEH药理学抑制剂中的任何一种可以增强eet在感觉和皮质神经元中的轴突增强活性。质谱分析表明，sEHi显著增加了神经元细胞培养中的eet，显著降低了二羟基二碳三烯酸代谢物。这些数据表明，EETs促进了轴突的生长，并表明轴突sEH活性调节了EETs诱导的轴突生长。这些发现提示了sEH抑制剂在促进神经再生中的一种新的治疗用途。
It has recently been reported that soluble epoxide hydrolase (sEH), the major enzyme that metabolizes epoxyeicosatrienoic acids (EETs), is expressed in axons of cortical neurons; however, the functional relevance of axonal sEH localization is unknown. Immunocytochemical analyses demonstrate predominant axonal localization of sEH in primary cultures of not only cortical but also sympathetic and sensory neurons. Morphometric analyses of cultured sensory neurons indicate that exposure to a regioisomeric mixture of EETs (0.01 to 1.0μM) cause a concentration-dependent increase in axon outgrowth. This axon promoting activity is not a generalized property of all regioisomers of EETs since axonal growth is enhanced in sensory neurons exposed to 14,15-EET but not 8,9 or 11,12-EET. 14,15-EET also promotes axon outgrowth in cultured cortical neurons. Co-exposure to EETs and either of two structurally diverse pharmacological inhibitors of sEH potentiate the axon-enhancing activity of EETs in sensory and cortical neurons. Mass spectrometry indicates that sEHi significantly increase EETs and significantly decrease dihydroxyeicosatrienoic acid metabolites in neuronal cell cultures. These data indicate that EETs enhance axon outgrowth and suggest that axonal sEH activity regulates EETs-induced axon outgrowth. These findings suggest a novel therapeutic use of sEH inhibitors in promoting nerve regeneration.
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影响因子：
3.2
作者：
Enayetallah, AE;French, RA;Grant, DF
通讯作者：
Grant, DF
影响因子：
8.3
作者：
Alkayed, NJ;Narayanan, J;Harder, DR
通讯作者：
Harder, DR
影响因子：
3.8
作者：
Howard, AS;Fitzpatrick, R;Lein, PJ
通讯作者：
Lein, PJ
DOI：
10.1016/0736-5748(96)00008-1
发表时间：
1996-06-01
影响因子：
1.8
作者：
Lein, P;Guo, X;Higgins, D
通讯作者：
Higgins, D
影响因子：
16.2
作者：
LEIN, P;JOHNSON, M;HIGGINS, D
通讯作者：
HIGGINS, D