Uptake and activation of eicosapentaenoic acid are related to accumulation of 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 with EPA respectively, had 2- to 3-fold higher uptake rate of EPA than the PUFA-resistant U-698 cell line. Furthermore, Ramos cells contained more lipid bodies and 3-fold more triacylglycerol than U-698 cells after 24 h incubation with 60 microm EPA. The mechanism behind the increased rate of EPA uptake in the PUFA-sensitive cell lines was examined by comparing the expression of 6 different fatty acid binding proteins (FABPs) and 3 acyl-CoA synthetases (ACSs) in U-698 and Ramos cells. Moreover, enzymatic activity of ACS and acyl-CoA:1,2-diacylglycerol acyltransferase (ADGAT) was investigated. The protein expression level of CD36 and p-FABPpm, the mRNA level of FABP, liver-FABP, heart-FABP, intestinal-FABP, ACS1, ACS2, and enzymatic ADGAT activity were similar in the two cell lines. However, an mRNA signal observed with 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 than U-698 cell lysate. In conclusion, the present findings indicate that cellular uptake, activation and incorporation of EPA into lipids may be related to induction of cell death in leukemia cell lines.
Finstad
H S
HS
Institute for Nutrition Research, University of Oslo, P.O. Box 1046, Blindern, 0316 Oslo, Norway.
Dyrendal
H
H
Myhrstad
M C
MC
Heimli
H
H
Drevon
C A
CA
D000217:Acyltransferases / Q000378:metabolism; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D051048:Diacylglycerol O-Acyltransferase; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins; D007938:Leukemia / Q000378:metabolism*; D018996:Myelin P2 Protein / Q000378:metabolism; D009363:Neoplasm Proteins; D019301:Oleic Acid / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D014280:Triglycerides; D019301:Oleic Acid; D015118:Eicosapentaenoic Acid; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase; D003066:Coenzyme A Ligases