PMID- 18513372 OWN - NLM STAT- MEDLINE DCOM- 20081103 LR - 20211020 IS - 1471-4159 (Electronic) IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 106 IP - 5 DP - 2008 Sep TI - Expression of E-FABP in PC12 cells increases neurite extension during differentiation: involvement of n-3 and n-6 fatty acids. PG - 2015-29 LID - 10.1111/j.1471-4159.2008.05507.x [doi] AB - Epidermal fatty acid-binding protein (E-FABP), a member of the family of FABPs, exhibits a robust expression in neurons during axonal growth in development and in nerve regeneration following nerve injury. This study examines the impact of E-FABP expression in normal neurite extension in differentiating pheochromocytoma cell (PC12) cultures supplemented with selected long chain free fatty acids (LCFFA). We found that E-FABP binds to a broad range of saturated and unsaturated LCFFAs, including those with potential interest for neuronal differentiation and axonal growth such as C22:6n-3 docosahexaenoic acid (DHA), C20:5n-3 eicosapentaenoic acid (EPA), and C20:4n-6 arachidonic acid (ARA). PC12 cells exposed to nerve growth factor (NGFDPC12) exhibit high E-FABP expression that is blocked by mitogen-activated protein kinase kinase (MEK) inhibitor U0126. Nerve growth factor-differentiated pheochromocytoma cells (NGFDPC12) antisense clones (NGFDPC12-AS) which exhibit low E-FABP expression have fewer/shorter neurites than cells transfected with vector only or NGFDPC12 sense cells (NGFDPC12-S). Replenishing NGFDPC12-AS cells with biotinylated recombinant E-FABP (biotin-E-FABP) protein restores normal neurite outgrowth. Cellular localization of biotin-E-FABP in NGFDPC12 was detected mostly in the cytoplasm and in the nuclear region. Treatment of NGFDPC12 with DHA, EPA, or ARA further enhances neurite length but it does not trigger further induction of TrkA or MEK phosphorylation or E-FABP mRNA observed in differentiating PC12 cells without LCFFA supplementation. Significantly, DHA and EPA neurite stimulating effects are higher in NGFDPC12-S than in NGFDPC12-AS cells. These findings are consistent with the scenario that neurite extension of differentiating PC12 cells, including further stimulation by DHA and EPA, requires sufficient cellular levels of E-FABP. FAU - Liu, Jo-Wen AU - Liu JW AD - Center for Health Disparities and Molecular Medicine, Department of Basic Science, Loma Linda University, California 92350, USA. FAU - Almaguel, Frankis G AU - Almaguel FG FAU - Bu, Liming AU - Bu L FAU - De Leon, Daisy D AU - De Leon DD FAU - De Leon, Marino AU - De Leon M LA - eng GR - P20 MD001632/MD/NIMHD NIH HHS/United States GR - P20 MD006988/MD/NIMHD NIH HHS/United States GR - 5R25GM060507/GM/NIGMS NIH HHS/United States GR - P20 MD001632-04/MD/NIMHD NIH HHS/United States GR - R25 GM060507/GM/NIGMS NIH HHS/United States GR - R25 GM060507-02/GM/NIGMS NIH HHS/United States GR - R25 GM060507-01A1/GM/NIGMS NIH HHS/United States GR - R25 GM060507-08/GM/NIGMS NIH HHS/United States GR - 5P20MD001632/MD/NIMHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20080530 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Eye Proteins) RN - 0 (Fabp5 protein, rat) RN - 0 (Fatty Acid-Binding Proteins) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Fatty Acids, Omega-6) RN - 0 (Nerve Tissue Proteins) RN - 0 (Oligodeoxyribonucleotides, Antisense) RN - 0 (Recombinant Fusion Proteins) RN - 25167-62-8 (Docosahexaenoic Acids) RN - 9061-61-4 (Nerve Growth Factor) RN - AAN7QOV9EA (Eicosapentaenoic Acid) RN - EC 2.7.12.2 (MAP Kinase Kinase 1) SB - IM MH - Animals MH - Cell Compartmentation/physiology MH - Cell Differentiation/drug effects/*physiology MH - Docosahexaenoic Acids/metabolism/pharmacology MH - Eicosapentaenoic Acid/metabolism/pharmacology MH - Eye Proteins/genetics/*metabolism MH - Fatty Acid-Binding Proteins/genetics/*metabolism MH - Fatty Acids, Omega-3/*metabolism/pharmacology MH - Fatty Acids, Omega-6/*metabolism/pharmacology MH - Lipid Metabolism/drug effects/*physiology MH - MAP Kinase Kinase 1/antagonists & inhibitors/metabolism MH - Nerve Growth Factor/metabolism/pharmacology MH - Nerve Tissue Proteins/genetics/*metabolism MH - Neurites/drug effects/*metabolism/ultrastructure MH - Oligodeoxyribonucleotides, Antisense/pharmacology MH - PC12 Cells MH - Protein Binding/drug effects/physiology MH - Rats MH - Recombinant Fusion Proteins/pharmacology PMC - PMC2785489 MID - NIHMS155546 EDAT- 2008/06/03 09:00 MHDA- 2008/11/04 09:00 PMCR- 2009/11/30 CRDT- 2008/06/03 09:00 PHST- 2008/06/03 09:00 [pubmed] PHST- 2008/11/04 09:00 [medline] PHST- 2008/06/03 09:00 [entrez] PHST- 2009/11/30 00:00 [pmc-release] AID - JNC5507 [pii] AID - 10.1111/j.1471-4159.2008.05507.x [doi] PST - ppublish SO - J Neurochem. 2008 Sep;106(5):2015-29. doi: 10.1111/j.1471-4159.2008.05507.x. Epub 2008 May 30.