The mitogen-induced lysophospholipid:acyl-CoA acyltransferase (LAT) expression in human T-lymphocytes is diminished...

One of the earliest changes observed in activated lymphocytes is the enhanced incorporation of unsaturated fatty acids into membrane phospholipids catalyzed by phospholipases and acyltransferases. This early membrane phospholipid remodeling has been shown to be independent from protein synthesis. We have investigated the oleic acid incorporation into phospholipids of activated T-lymphocytes within hours and present data that the sustained membrane phospholipid remodeling in activated T-lymphocytes was largely decreased by cycloheximide and actinomycin D treatment while neither protein synthesis inhibitor had an effect on the fatty acid incorporation into phospholipids in resting T-lymphocytes. Lisofylline, an inhibitor of lysophosphatidic acid:acyl-CoA acyltransferase, had no inhibitory activity, indicating that the membrane lipid remodeling was not due to fatty acid incorporation into de novo-synthesized phospholipids. The membrane phospholipid alteration induced by mitogens was also diminished by hydrocortisone (HC) in a concentration-dependent manner. The steroid hormone antagonist RU486 failed to reverse but potentiated this inhibitory activity of HC. HC did not affect the fatty acid uptake, and the decrease of fatty acid incorporation into phospholipids induced by HC was accompanied by an increase of fatty acid incorporation into triglycerides, indicating that the inhibitory activity of HC was specific for fatty acid incorporation into phospholipids catalyzed by lysophospholipidacyl-CoA acyltransferase (LAT). HC did not directly inhibit the LAT enzyme activity. From these data we conclude that LAT gene transcription is induced as an early event following T-cell activation. The inhibitory action of hydrocortisone may give new insights into the regulatory mechanisms involved in LAT expression.