Synthesis of nuclear lipids in L 2C leukemic lymphocytes

Abstract

We previously reported that propiconazole strongly inhibits cholesterol synthesis, but not cell division in a stimulated cell, the human lymphocyte cultured with phytohemagglutinin, showing that newly synthesized cholesterol is not necessary for cell division. In this study we labeled the L2C leukemic guinea pig lymphocyte, a naturally stimulated cell, with [2-14C]acetate, and compared the composition of newly synthesized lipids isolated from nuclei and whole cells (or microsomes). We observed that the proportion of cholesterol in labeled non-saponifiable lipids extracted from nuclei was lower than in non-saponifiable lipids isolated from whole cells, whereas the proportion of squalene and polar lipids was higher. By analyzing total lipid extracts, the polar lipids were identified as alkylglycerols, and the above mentioned distribution of constituents was confirmed. The identification of alkylglycerols was also supported by the comparison of radioactive lipid composition after labeling cells with three different lipid precursors: [2-14C]mevalonate, [2-14C]acetate and [2-14C]stearate. When cells were labeled in the presence of dodecylimidazole, the percentage of squalene and alkylglycerols decreased in nuclear lipids, but was not altered when cells were cultured in the presence of propiconazole, a cholesterol synthesis inhibitor which does not affect cell division of human stimulated lymphocytes. We have shown that dodecylimidazole inhibited alkylglycerol biosynthesis and squalene uptake by the nucleus, suggesting that these compounds could play a role in the regulation of cell division.