PMID- 21155804 OWN - NLM STAT- MEDLINE DCOM- 20110621 LR - 20211020 IS - 1471-4159 (Electronic) IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 117 IP - 4 DP - 2011 May TI - Epoxyeicosatrienoic acids enhance axonal growth in primary sensory and cortical neuronal cell cultures. PG - 632-42 LID - 10.1111/j.1471-4159.2010.07139.x [doi] AB - 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 (0.01-1.0 muM) causes a concentration-dependent increase in axon outgrowth. This axon promoting activity is not a generalized property of all regioisomers of EETs as 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 potentiates the axon-enhancing activity of EETs in sensory and cortical neurons. Mass spectrometry indicates that sEH inhibition significantly increases EETs and significantly decreases 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. CI - (c) 2011 The Authors. Journal of Neurochemistry (c) 2011 International Society for Neurochemistry. FAU - Abdu, Emun AU - Abdu E AD - Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA. FAU - Bruun, Donald A AU - Bruun DA FAU - Yang, Dongren AU - Yang D FAU - Yang, Jun AU - Yang J FAU - Inceoglu, Bora AU - Inceoglu B FAU - Hammock, Bruce D AU - Hammock BD FAU - Alkayed, Nabil J AU - Alkayed NJ FAU - Lein, Pamela J AU - Lein PJ LA - eng GR - NS044313/NS/NINDS NIH HHS/United States GR - P42ES004699/ES/NIEHS NIH HHS/United States GR - ES014901/ES/NIEHS NIH HHS/United States GR - R01 ES002710/ES/NIEHS NIH HHS/United States GR - P42 ES004699/ES/NIEHS NIH HHS/United States GR - R01 ES002710-31/ES/NIEHS NIH HHS/United States GR - R01 NS046649-05/NS/NINDS NIH HHS/United States GR - R01 ES014901/ES/NIEHS NIH HHS/United States GR - P30 NS061800/NS/NINDS NIH HHS/United States GR - R01 NS044313/NS/NINDS NIH HHS/United States GR - R56 ES014901/ES/NIEHS NIH HHS/United States GR - ES002710/ES/NIEHS NIH HHS/United States GR - R01 NS044313-01/NS/NINDS NIH HHS/United States GR - R01 NS046649/NS/NINDS NIH HHS/United States GR - NS046649/NS/NINDS NIH HHS/United States GR - R01 NS070837/NS/NINDS NIH HHS/United States GR - P42 ES004699-23S2/ES/NIEHS NIH HHS/United States GR - R01 ES014901-02/ES/NIEHS NIH HHS/United States GR - R37 ES002710/ES/NIEHS NIH HHS/United States GR - R01 ES002710-30/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110124 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Eicosanoic Acids) RN - EC 3.3.2.- (Epoxide Hydrolases) SB - IM MH - Animals MH - Axons/*physiology MH - Cell Count MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cerebral Cortex/cytology/drug effects/*physiology MH - Dose-Response Relationship, Drug MH - Eicosanoic Acids/*pharmacology MH - Epoxide Hydrolases/metabolism MH - Female MH - Ganglia, Spinal/cytology/drug effects MH - Immunohistochemistry MH - Neurons/drug effects MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Sensory Receptor Cells/drug effects/*physiology MH - Subcellular Fractions/metabolism MH - Sympathetic Nervous System/cytology/drug effects PMC - PMC3081369 MID - NIHMS257940 EDAT- 2010/12/16 06:00 MHDA- 2011/06/22 06:00 PMCR- 2012/05/01 CRDT- 2010/12/16 06:00 PHST- 2010/12/16 06:00 [entrez] PHST- 2010/12/16 06:00 [pubmed] PHST- 2011/06/22 06:00 [medline] PHST- 2012/05/01 00:00 [pmc-release] AID - 10.1111/j.1471-4159.2010.07139.x [doi] PST - ppublish SO - J Neurochem. 2011 May;117(4):632-42. doi: 10.1111/j.1471-4159.2010.07139.x. Epub 2011 Jan 24.