CHANGES IN ARACHIDONIC-ACID LEVELS AND FORMATION AND IN LIPID-SYNTHESIS IN THE HUMAN NEUROBLASTOMA SK-N-BE DURING RETINOIC ACID-INDUCED DIFFERENTIATION

We observed that retinoic acid, which differentiates the human neurobl astoma SK-N-BE into mature neurons, induced an elevation in levels of polyunsaturated fatty acids, especially arachidonic acid (20:4 n-6), T his effect was not induced by phorbol myristate acetate, another diffe rentiating agent, We then explored the effects of retinoic acid on the formation of arachidonic acid and of docosahexaenoic acid from precur sors and on the de novo lipid synthesis from acetate at various stages of differentiation, which was assessed by morphological (cell number and neurite outgrowth) and biochemical (protein content and thymidine incorporation) criteria, At 3 days of incubation with retinoic acid, i n the n-6 series, total conversion of linoleic acid, especially to 20: 3 n-6, was elevated, in association with preferential incorporation of acetate into phospholipids; in contrast, at 8 days, synthesis of 20-c arbon polyunsaturated fatty acids declined, in association with enhanc ed incorporation in triglycerides. In the n-3 series, eicosapentaenoic acid was converted to docosahexaenoic acid in SK-N-BE, but the conver sion was not affected by retinoic acid, During the early stage of neur onal differentiation, therefore, enhanced production of 20-carbon poly unsaturated fatty acids from their precursors occurred, and newly form ed fatty acids were preferentially incorporated in phospholipids, poss ibly in association with membrane deposition, When differentiation was completed, arachidonic acid formation and incorporation of acetate in phospholipids and cholesterol declined with enhanced labeling of stor age lipids.