Effects of cholesterol on viability and (n - 6) fatty acid metabolism in cultured human monocyte-like cells (U937)

• Published in: Biochemistry and cell biology Vol. 70; no. 8; p. 643
• Main Authors: Howie, A, Huang, Y S, Horrobin, D F
• Format: Journal Article
• Language: English
• Published: Canada 01.08.1992
• Subjects: Cell Death - drug effects; Cell Division - drug effects; Cholesterol - pharmacology; Fatty Acids, Omega-6; Fatty Acids, Unsaturated - metabolism; Fatty Acids, Unsaturated - toxicity; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids - pharmacology; Linolenic Acids - pharmacology; Lipid Peroxidation - drug effects; Monocytes - drug effects; Tumor Cells, Cultured
• ISSN: 0829-8211
• DOI: 10.1139/o92-099

Effects of supplementation of growth-promoting cholesterol on metabolism of the cytotoxic (n - 6) polyunsaturated fatty acids in cultured human monocyte-like cells (U937) have been examined. U937 cells were incubated in 5% delipidated fetal bovine serum containing 0 or 38.7 microM cholesterol. The rate of uptake and the distribution of metabolites of (n - 6) fatty acids (such as 18:2(n - 6), 18:3(n - 6), and 20:3(n - 6), and 20:4(n - 6)) were examined by adding radiolabelled fatty acid at a level of 1 microgram/mL (3.3 microM for 20-carbon fatty acids and 3.6 microM for 18-carbon-fatty acids). For assessing the cytotoxicity, (n - 6) fatty acids were added to medium at a concentration of 5 micrograms/mL (16.4 microM for 20-carbon fatty acids and 17.9 microM for 18-carbon fatty acids). Cholesterol supplementation suppressed the uptake of all (n - 6) fatty acids and reduced the cytotoxic effects of 18:2(n - 6), 20:3(n - 6), and 20:4(n - 6), but not 18:3(n - 6). In addition, cholesterol supplementation increased peroxide production and metabolism of (n - 6) fatty acids in U937 cells. Thus, the differential suppressive effect of cholesterol on the cytotoxicity of different fatty acids could not be attributed to an inhibitory effect on fatty acid delta 6- and delta 5-desaturation, or to an antioxidant effect on peroxide formation.