Apoptosis

    

Staurosporine (ST) induces apoptotic cell death of Neuro 2A cells, which is significantly inhibited by prior enrichment with DHA, but not oleic and arachidonic acids. Phosphatidylinositol 3-kinase (PI3-K) inhibitors, wortmanin, and LY-294002 abolished the protective effect of DHA. The extent of the antiapoptotic effect of DHA is mediated at least in part through the PI3-K/Akt pathway, facilitated by DHA-induced PS accumulation. Akbar M, Kim HY. Protective effects of docosahexaenoic acid in staurosporine-induced apoptosis: involvement of phosphatidylinositol-3 kinase pathway. J Neurochem 2002 Aug; 82(3): 655-65

    DHA enrichment increased PS in cultured neuronal cells and protected against apoptotic cell death (cell suicide) in a subsequent absence of growth factors. Kim HY, Akbar M, Lau A, Edsall L. Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6n-3): Role of phosphatidylserine in antiapoptotic effect. J Biol Chem 2000; M004446200

Enrichment of neuronal cells with DPAn-6 increased the total PS content in comparison to non-enriched control significantly less than enrichment with DHAn-3, primarily due to the fact that 18:0,22:5n-6 not as effectively accumulated as 18:0,22:6n-3 in PS. As with DHA, DPA enrichment protected Neuro 2A cells against apoptotic cell death induced by the staurosporine treatment, but to a lesser extent. The in vitro interaction between Raf-1 and membrane was affected not only by the PS content but also by the fatty acyl composition in PS. Reduction of PS concentration in liposomes, as well as substitution of 18:0,22:6 with 16:0,18:1, considerably reduced interaction with Raf-1. Thus, depletion of DHAn-3 from neuronal tissues may have a compounding effect on Raf-1 translocation in growth factor signaling. The fact that DPAn-6 cannot fully support the protective role played by DHA may explain the adverse effect of n-3 fatty acid deficiency on neuronal development and function. Hee-Yong Kim, Mohammed Akbar and Audrey Lau, Effects of Docosapentaenoic Acid on Neuronal Apoptosis 2004, Lipids, 38, 453-457.