Inhibition of Neuronal Apoptosis by Polyunsaturated Fatty Acids

ISSN： 0895-8696

Source： Journal of Molecular Neuroscience, Vol.16, Iss.2-3, 2001-07, pp. : 223-228

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Abstract

The effect of polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (226n-3; DHA) and arachidonic acid (204n-6; AA), on apoptotic cell death was evaluated based on DNA fragmentation and caspase-3 activity induced by serum starvation using Neuro-2A and PC-12 cells. The presence of 204n-6 in the medium during serum starvation decreased DNA fragmentation and this initial protective effect was diminished with prolonged serum starvation. The observed protective effect of 20:4n-6 was not affected by the inhibitors of cyclooxygenase (COX) and lipoxygenase. Conversely, 226n-3 became protective only after the enrichment of cells with this fatty acid at least for 24 h prior to the serum deprivation. DNA fragmentation as well as caspase-3 activity was reduced in 226n-3 enriched cells with a concomitant decrease in protein and mRNA levels. During the enrichment period, 226n-3 steadily increased its incorporation into PS leading to a significant increase in the total PS content; the protective effect of 226n-3 paralleled the PS accumulation. Neither direct exposure of cells to nor enrichment with 181n-9 had any protective effect. In conclusion, it is proposed that 204n-6 prevents neuronal apoptosis primarily due to the action of nonesterified 204n-6 but 226n-3, at least in part, through PS accumulation.