Omega-3 polyunsaturated fatty acids increase purine but not pyrimidine transport in L1210 leukaemia cells.
Here we show that in vitro supplementation of L1210 murine lymphoblastic leukaemia cells with n-3 polyunsaturated fatty acids results in considerable changes in the fatty acid composition of membrane phospholipids. Incubations for 48 h with 30 microM eicosapentaenoic acid (20:5, n-3; EPA) or docosahexaenoic acid (22:6, n-3; DHA) results primarily in substitution of long chain n-6 fatty acids with long-chain n-3 fatty acids. This results in a decrease in the n-6/n-3 ratio from 6.9 in unsupplemented cultures to 1.2 or 1.6 for EPA and DHA supplemented cultures, respectively. Coincident with these changes in membrane fatty acid composition, we observed a 5-fold increase in the rate of adenosine (5 microM) uptake via a nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporter in EPA- and DHA-supplemented L1210 cells, relative to unsupplemented cells. This seemed to result from a decrease in the Km for adenosine from 12.5 microM in unsupplemented cultures to 5.1 microM in DHA-treated cultures. Guanosine (50 microM) transport was similarly affected by DHA with a 3.5-fold increase in the initial rate of uptake. In contrast, pyrimidine transport, as measured by uptake of thymidine and cytidine, was not similarly affected, suggesting that substrate recognition had been altered by fatty acid supplementation. Studies using [(3)H]NBMPR showed that there was no effect of EPA or DHA on either the number of NBMPR-binding sites or the affinity of these sites for NBMPR. This observation suggests that the increases in adenosine and guanosine transport were not due to increases in the number of transported sites but rather that EPA and DHA directly or indirectly modulate transporter function.
Martin
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Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada.
Meckling-Gill
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D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D011687:Purines / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D013268:Stimulation, Chemical; D013379:Substrate Specificity
D015525:Fatty Acids, Omega-3; D011687:Purines; D011743:Pyrimidines