Manipulation of the fate of long chain polyunsaturated fatty acids in cultured cells.
We have studied the biosynthesis of long chain polyunsaturated fatty acids (LC-PUFA) from their precursors in cultured cells undergoing physiological modifications, or under the influence of lipid-lowering drugs or ethanol. The formation of arachidonic acid (AA, 20:4 n-6) from the percursor linoleic acid (LA, 18:2 n-6) in the neuroblastoma cells SK-N-BE is enhanced at early stages of differentiation, and declines when differentiation is complete, in concomitance with maximal accumulation of AA in cell lipids. In the monocytic cells THP-1, the biosynthesis of LC-PUFA is also enhanced by treatment with the HMGCoA reductase inhibitor simvastatin (S), an effect which is reverted by mevalonate and other intermediates of cholesterol synthesis. Maximal activation of LC-PUFA synthesis by S occurs at concentrations lower than those required for maximal inhibition of cholesterol synthesis. In the hepatoma cells HepG2, ethanol decreases the biosynthesis of LC-PUFA while potentiating the incorporation of acetate into cholesterol. LC-PUFA synthesis appears thus to be modulated in the course of cell differentiation and complex interactions between LC-PUFA and cholesterol synthesis occur, as judged from data obtained through pharmacological manipulations.
Galli
C
C
Institute of Pharmacological Sciences, School of Pharmacy, University of Milan, Italy.
Risé
P
P
Marangoni
F
F
Petroni
A
A
Visioli
F
F
D016718:Arachidonic Acid / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D008798:Mevalonic Acid / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D019821:Simvastatin; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008041:Linoleic Acids; D016718:Arachidonic Acid; D000431:Ethanol; D002784:Cholesterol; D019787:Linoleic Acid; D008148:Lovastatin; D019821:Simvastatin; D008798:Mevalonic Acid