Influence of cellular arachidonic acid levels on phospholipid remodeling and CoA-independent transacylase activity in human monocytes and U937 cells

• Published in: Biochimica et biophysica acta 2011-02, Vol.1811 (2), p.97-103
• Main Authors: Astudillo, Alma M., Pérez-Chacón, Gema, Balgoma, David, Gil-de-Gómez, Luis, Ruipérez, Violeta, Guijas, Carlos, Balboa, María A., Balsinde, Jesús
• Format: Article
• Language: English
• Subjects: Acyltransferases - metabolism; Arachidonic acid; Arachidonic Acid - metabolism; CoA-independent transacylase; Coenzyme A - metabolism; Free fatty acid; Humans; Membrane Lipids - metabolism; Monocytes - cytology; Monocytes - metabolism; Phospholipase A2; Phospholipid remodeling; Phospholipids - metabolism; U937 Cells
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2010.11.009

The availability of free arachidonic acid (AA) constitutes a limiting step in the synthesis of biologically active eicosanoids. Free AA levels in cells are regulated by a deacylation/reacylation cycle of membrane phospholipids, the so-called Lands cycle, as well as by further remodeling reactions catalyzed by CoA-independent transacylase. In this work, we have comparatively investigated the process of AA incorporation into and remodeling between the various phospholipid classes of human monocytes and monocyte-like U937 cells. AA incorporation into phospholipids was similar in both cell types, but a marked difference in the rate of remodeling was appreciated. U937 cells remodeled AA at a much faster rate than human monocytes. This difference was found not to be related to the differentiation state of the U937 cells, but rather to the low levels of esterified arachidonate found in U937 cells compared to human monocytes. Incubating the U937 cells in AA-rich media increased the cellular content of this fatty acid and led to a substantial decrease of the rate of phospholipid AA remodeling, which was due to reduced CoA-independent transacylase activity. Collectively, these findings provide the first evidence that cellular AA levels determine the amount of CoA-independent transacylase activity expressed by cells and provide support to the notion that CoA-IT is a major regulator of AA metabolism in human monocytes. ► Phospholipid arachidonate remodeling in U937 cells is faster than in human monocytes. ► Arachidonate remodeling does not depend on the differentiation stage of the cells. ► The intracellular content of arachidonate determines the rate of remodeling. ► Arachidonate‐loaded U937 cells exhibit a reduced CoA-transacylase activity.