Eicosapentaenoic acid (EPA) increases cell viability and expression of neurotrophin receptors in retinoic acid and brain-derived neurotrophic factor differentiated SH-SY5Y cells

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 p75NTR 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 µM) 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 µM) significantly increased the full-length TrkB (TrkBTK+), but not truncated TrkB (TrkBTK−) expression in these cells. An increase in p75NTR expression was also observed with 10.0 µM 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.

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Acknowledgments

This work was supported by grant from Canadian Institute of Health Research (CIHR) to C. Song and Industry-partnered postdoctoral fellowship from CIHR to W. Kou. We would like to thank Amarin Neuroscience Ltd for providing financial support and Dr. Michael Mayne for providing research facilities at NRC-INH for this study. Technical assistance provided by Mr. Di Shao, Ms. Charlene Supnet and Mr. Jeff Grant is appreciated.

Author informationAuthors and Affiliations

Dept. of Biomedical Sciences, AVC, University of Prince Edward Island and NRC Institute for Nutrisciences and Health, Charlottetown, PE, Canada

Wei Kou, Dirk Luchtman & Cai Song MD, PhD

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Correspondence to Cai Song MD, PhD.

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Kou, W., Luchtman, D. & Song, C. Eicosapentaenoic acid (EPA) increases cell viability and expression of neurotrophin receptors in retinoic acid and brain-derived neurotrophic factor differentiated SH-SY5Y cells. Eur J Nutr 47, 104–113 (2008). https://doi.org/10.1007/s00394-008-0703-1

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Received: 13 June 2007

Accepted: 05 March 2008

Published: 23 March 2008

Issue Date: March 2008

DOI: https://doi.org/10.1007/s00394-008-0703-1