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Inhibition of Neuronal Apoptosis by Docosahexaenoic Acid (22:6n-3)
Open accessAbstract
Enrichment of Neuro 2A cells with docosahexaenoic acid (22:6n-3) decreased apoptotic cell death induced by serum starvation as evidenced by the reduced DNA fragmentation and caspase-3 activity. The protective effect of 22:6n-3 became evident only after at least 24 h of enrichment before serum starvation and was potentiated as a function of the enrichment period. During enrichment 22:6n-3 incorporated into phosphatidylserine (PS) steadily, resulting in a significant increase in the total PS content. Similar treatment with oleic acid (18:1n-9) neither altered PS content nor resulted in protective effect. Hindering PS accumulation by enriching cells in a serine-free medium diminished the protective effect of 22:6n-3. Membrane translocation of Raf-1 was significantly enhanced by 22:6n-3 enrichment in Neuro 2A cells. Consistently, in vitro biomolecular interaction between PS/phosphatidylethanolamine /phosphatidylcholine liposomes, and Raf-1 increased in a PS concentration-dependent manner. Collectively, enrichment of neuronal cells with 22:6n-3 increases the PS content and Raf-1 translocation, down-regulates caspase-3 activity, and prevents apoptotic cell death. Both the antiapoptotic effect of 22:6n-3 and Raf-1 translocation are sensitive to 22:6n-3 enrichment-induced PS accumulation, strongly suggesting that the protective effect of 22:6n-3 may be mediated at least in part through the promoted accumulation of PS in neuronal membranes.
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Trophic factors and neuronal survival
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Cited by
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Self-citationMarcheselli, V. L., Hong, S., Lukiw, W. J., Tian, X. H., Gronert, K., Musto, A., Hardy, M., Gimenez, J. M., Chiang, N., Serhan, C. N., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305841200 · Cited by 802
Mukherjee, P. K., Marcheselli, V. L., Serhan, C. N., & Bazan, N. G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402531101 · Cited by 753
Lipids and Alzheimer’s Disease
Kao, Y.-C., Ho, P.-C., Tu, Y.-K., Jou, I.-M., & Tsai, K.-J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041505 · Cited by 485
Modulation of inflammation in brain: A matter of fat
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Metadata
- Authors
- Kim, H.-Y., Akbar, M., Lau, A., & Edsall, L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-11
- Volume
- 275
- Issue
- 45
- Pages
- 35215-35223
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1967380123
- Cited by
- 308
- References
- 4
- FWCI
- 9.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Kim, H.-Y., Akbar, M., Lau, A., & Edsall, L. (2000). Inhibition of Neuronal Apoptosis by Docosahexaenoic Acid (22:6n-3). Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m004446200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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