Diacylglycerol-containing oleic acid induces increases in [Ca2+]i via TRPC3/6 channels in human T-cells

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids Vol. 1821; no. 4; pp. 618 - 626
• Main Authors: Carrillo, Celia, Hichami, Aziz, Andreoletti, Pierre, Cherkaoui-Malki, Mustapha, del Mar Cavia, María, Abdoul-Azize, Souleymane, Alonso-Torre, Sara R., Khan, Naim Akhtar
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.04.2012
• Subjects: arachidonic acid; calcium; Calcium channels; Calcium signaling; Diacylglycerols; dose response; Fatty acids; free fatty acids; genes; humans; hydrolysis; Lipids; oleic acid; phospholipids; plasma membrane; shRNA; T-cells; T-lymphocytes; TRPC3; TRPC6; T-cells; Calcium signaling; Calcium channels; TRPC6; TRPC3; shRNA; Lipids; Diacylglycerols; Fatty acids
• ISSN: 1388-1981; 1879-2618
• DOI: 10.1016/j.bbalip.2012.01.008

Though most of the studies have focused on the effects of free fatty acids on T-cell activation, fatty acids incorporated into plasma membrane phospholipids may also affect cell signaling via diacylglycerol (DAG), generally produced by phospholipid hydrolysis. In the present study, we have synthesized a DAG-containing oleic acid and studied its implication in the modulation of calcium signaling in human Jurkat T-cells. 1-palmitoyl-2-oleoyl-sn-glycerol (POG) induced a dose-dependent increase in [Ca2+]i. This effect was due to the presence of oleic acid at the sn-2 position as no differences were observed between POG and 1-stearoly-2-oleoyl-sn-glycerol (SOG). However, the substitution of oleic acid with arachidonic acid at the sn-2 position of the DAG moiety exerted a different response on the increases in [Ca2+]i in these cells. POG-evoked increases in [Ca2+]i were not due to its metabolites. Furthermore, POG-induced increases in [Ca2+]i were due to the opening of TRPC3/TRPC6 channels as silencing of TRPC3 and TRPC6 genes by shRNA abolished calcium entry. Moreover, disruption of lipid rafts with methyl-β-cyclodextrin completely abolished POG-evoked increases in [Ca2+]i. In conclusion, our results demonstrate that oleic acid can influence T-lymphocyte functions, in the conjugated form of DAG, via opening TRPC3/6 channels. ► DAG-containing OA induces increases in [Ca2+]i in human T-cells. ► Such increases are via opening of TRPC3 and TRPC6 channels. ► Oleic acid at the sn-2 position confers the molecular property to the diacylglycerol. ► Disruption of lipid rafts completely abolished POG-evoked increases in [Ca2+]i.