Biosynthesis of unsaturated fatty acids in the main cell lineages of human leukemia and lymphoma

Abstract

Unsaturated fatty acids are essential for the proliferation of many haematopoietic cells, but little is known about their biosynthetic pathways in these cells. We have studied the activity of the main desaturation-elongation enzymes in human B-(Reh-6, Raji, Ramos) and T-(CEM, Jurkat) lymphocytic, promonocytic (U937), promyelocytic (HL-60) and pluripotent myeloid (K562) cell lineages, as well as the changes induced by cell differentiation. Cells were incubated with 14C-labelled 18:0, 18:2 ( n - 6) and 18:3( n- 3) or supplemented with the corresponding unlabelled fatty acid and synthesis of polyunsaturated fatty acids (PUFA) was evaluated by argentation-TLC and GLC. The main activity present in most cells was Δ 9-desaturase (range between 200–1000 pmol/24 h per 10 6 cells) that was regulated by th type of free fatty acids in culture media. A great variability in the activities of Δ 6-and Δ 5-desaturase was observed. They wer virtually absent in B-cells and only one (Jurkat) T-cell line synthesized significant amounts of ( n - 6) and ( n - 3) PUFA. The main PUFA formed by Jurkat cells were 20:3 and 20:4( n - 6) (30 and 40%, respectively of cell lipid radioactivity) and 20:5, 22:5 and 22:6( n -3) (60, 20 and 10%, respectively, of cell radioactivity). Cell differentiation caused complex changes in desaturase activities. The activity of Δ 9-desaturase increased with the degree of differentiation of B-cells. Differentiation of U937 cells to macrophages with PMA caused a 2–3-fold increase in the activity of ( Δ 6 + Δ 5)-and Δ 9-desaturases and no changes and a 2-fold decrease, respectively, i the inducer was DMSO. Differentiation of HL-60 cells to granulocytes with DMSO virtually abolished Δ 9-desaturase activity and greatly reduced that of Δ 6-and Δ 5-desaturases. Δ 9-Desaturase activity increased (2.5-fold) in myeloid K562 cells differentiated to erythroblasts with hemin. No induction of Δ 6-desaturase, absent in K562 cells, occurred after differentiation to erythroblasts or megakaryoblasts and they synthesized alternative PUFA through sequential elongation and Δ 5-desaturation of 18:2( n - 6) and 18:3( n - 3). The activities of Δ 6-and Δ 5-desaturase in HL-60 and U937 cells increased when differentiation also stimulated the synthesis of eicosanoids and extracellular release of PUFA.