Uptake and activation of eicosapentaenoic acid are related to accumulationof triacylglycerol in Ramos cells dying from apoptosis

The present study investigates the mechanism behind induction of cell death by eicosapentaenoic acid (EPA) in leukemia cells. The PUFA-sensitive cell lines Raji and Ramos, which die by necrosis and apoptosis upon incubation w ith EPA respectively, had 2- to S-fold higher uptake rate of EPA than the P UFA-resistant U-698 cell line. Furthermore, Ramos cells contained more lipi d bodies and 3-fold more triacylglycerol than U-698 cells after 24 h incuba tion with 60 mu M EPA. The mechanism behind the increased rate of EPA uptak e in the PUFA-sensitive cell lines was examined by comparing the expression of 6 different fatty acid binding proteins (FABPs) and 3 acyl-CoA syntheta ses (ACSs) in U-698 and Ramos cells. Moreover, enzymatic activity of ACS an d acyl-CoA:1,2-diacylglycerol acyltransferase (ADGAT) was investigated. The protein expression level of CD36 and p-FABPpm, the mRNA level of FABP, liv er-FABP, heart-FABP, intestinal-FABP, ACS1, ACS2, and enzymatic ADGAT activ ity were similar in the two cell lines. However, an mRNA signal observed wi th a probe for ACS3 was 1.7 times higher in Ramos than in U-698 cells, and lysate from Ramos cells had a higher capacity to activate EPA to EPA-CoA th an U-698 cell lysate. In conclusion, the present findings indicate that cel lular uptake, activation and incorporation of EPA into lipids map be relate d to induction of cell death in leukemia cell. lines.