MANIPULATION OF THE FATE OF LONG-CHAIN POLYUNSATURATED FATTY-ACIDS INCULTURED-CELLS

We have studied the biosynthesis of long chain polyunsaturated fatty a cids (LC-PUFA) from their precursors in cultured cells undergoing phys iological modifications, or under the influence of lipid-lowering drug s or ethanol. The formation of arachidonic acid (AA, 20:4 n-6) from th e percursor linoleic acid (LA, 18:2 n-6) in the neuroblastoma cells SK -N-BE is enhanced at early stages of differentiation, and declines whe n differentiation is complete, in concomitance with maximal accumulati on of AA in cell lipids. In the monocytic cells THP-1, the biosynthesi s of LC-PUFA is also enhanced by treatment with the HMGCoA reductase i nhibitor simvastatin (S), an effect which is reverted by mevalonate an d other intermediates of cholesterol synthesis. Maximal activation of LC-PUFA synthesis by S occurs at concentrations lower than those requi red for maximal inhibition of cholesterol synthesis. In the hepatoma c ells HepG2, ethanol decreases the biosynthesis of LC-PUFA while potent iating the incorporation of acetate into cholesterol. LC-PUFA synthesi s appears thus to be modulated in the course of cell differentiation a nd complex interactions between LC-PUFA and cholesterol synthesis occu r, as judged from data obtained through pharmacological manipulations.