PMID- 18360785 OWN - NLM STAT- MEDLINE DCOM- 20080527 LR - 20211020 IS - 1436-6207 (Print) IS - 1436-6207 (Linking) VI - 47 IP - 2 DP - 2008 Mar TI - Eicosapentaenoic acid (EPA) increases cell viability and expression of neurotrophin receptors in retinoic acid and brain-derived neurotrophic factor differentiated SH-SY5Y cells. PG - 104-13 LID - 10.1007/s00394-008-0703-1 [doi] AB - BACKGROUND: The n-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA) has been found to process neuroprotective effects. However, the exact cellular mechanisms are not well understood. Brain-derived neurotrophic factor (BDNF) is one of neurotrophins, which is involved in neuron differentiation, survival, and synaptogenesis. AIM OF THE STUDY: In this study, the potential neuroprotective effects of EPA, and its possible effects on BDNF and BDNF receptor expression were investigated in SH-SY5Y cells. METHODS: Both undifferentiated and retinoic acid (RA)-BDNF differentiated SH-SY5Y cells were treated with EPA and/or BDNF. The cell viability was determined by MTT assay. The expression of BDNF receptors, tyrosine kinase receptor B (TrkB) and p75(NTR) were tested by RT-PCR and Western blotting. RESULTS: In undifferentiated SH-SY5Y cells, either EPA or BDNF, or both did not affect the cell viability. In RA-BDNF differentiated SH-SY5Y cells, treatment with different doses of EPA (0.01, 0.1, 1.0, 10.0 microM) and BDNF (1 ng/ml) for 24 hours significantly increased the cell viability, while EPA or BDNF alone showed no effect. More importantly, RT-PCR and Western blotting results revealed that 24 hours treatment with EPA (0.01, 0.1, 1.0 microM) significantly increased the full-length TrkB (TrkB(TK+)), but not truncated TrkB (TrkB(TK-)) expression in these cells. An increase in p75(NTR) expression was also observed with 10.0 microM EPA treatment. Finally, co-incubation with either 100 nM staurosporine, a protein kinase inhibitor, or 500 nM K252a, a tyrosine kinase inhibitor completely abolished the EPA-induced increase in cell viability. CONCLUSIONS: Our results indicate that EPA exerts beneficial effects on cell survival through modulating neurotrophin receptor expression. FAU - Kou, Wei AU - Kou W AD - Dept. of Biomedical Sciences, AVC, University of Prince Edward Island, Charlottetown (PE), Canada. FAU - Luchtman, Dirk AU - Luchtman D FAU - Song, Cai AU - Song C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080323 PL - Germany TA - Eur J Nutr JT - European journal of nutrition JID - 100888704 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Fatty Acids, Unsaturated) RN - 0 (Receptors, Nerve Growth Factor) RN - 5688UTC01R (Tretinoin) RN - AAN7QOV9EA (Eicosapentaenoic Acid) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/drug effects/*metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - *Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - Eicosapentaenoic Acid MH - Fatty Acids, Unsaturated/*pharmacology MH - Humans MH - Receptor, trkB/drug effects/metabolism MH - Receptors, Nerve Growth Factor/*drug effects/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tretinoin/metabolism EDAT- 2008/03/25 09:00 MHDA- 2008/05/28 09:00 CRDT- 2008/03/25 09:00 PHST- 2007/06/13 00:00 [received] PHST- 2008/03/05 00:00 [accepted] PHST- 2008/03/25 09:00 [pubmed] PHST- 2008/05/28 09:00 [medline] PHST- 2008/03/25 09:00 [entrez] AID - 10.1007/s00394-008-0703-1 [doi] PST - ppublish SO - Eur J Nutr. 2008 Mar;47(2):104-13. doi: 10.1007/s00394-008-0703-1. Epub 2008 Mar 23.