Speaker: Hee-Yong Kim, Laboratory of Membrane Biochemistry and Biophysics, NIAAA, NIH, Bethesda, MD

Topic: Cell Membrane Modification by Docosahexaenonic Acid: Effects on Neuronal Apoptosis

Place: Building 426, Conference Room, NCI-Frederick, Frederick, MD

Time: Tuesday, April 10, 2001, at 2:00 PM

Abstract: Docosahexaenoic acid (22:6n-3) is the most abundant polyunsaturated fatty acid found in neuronal cells and is known to be essential for proper neuronal function. As an attempt to understand biochemical and biological functions of this fatty acid underlying its essentiality, the effect of 22:6n-3 on apoptotic neuronal cell death was investigated in relation to its ability to modify membrane constituents. 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 24h of enrichment prior to serum starvation and was potentiated as a function of enrichment period. During enrichment 22:6n-3 incorporated into 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/PE/PC 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, downregulates 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.