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

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• 作者：Celia Carrillo^a ; Aziz Hichami^b ; Pierre Andreoletti^c ; ^d ; Mustapha Cherkaoui-Malki^c ; ^d ; Marí ; a del Mar Cavia^a ; Souleymane Abdoul-Azize^b ; Sara R. Alonso-Torre^a ; ¹ ; ^{salonso@ubu.es} ; Naim Akhtar Khan^b ; ¹
• 关键词：Diacylglycerols ; T-cells ; Fatty acids ; Lipids ; Calcium channels ; Calcium signaling ; TRPC3 ; TRPC6 ; shRNA
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2012
• 期刊代码：18_13881981
• 类别：bio
• 出版时间：April, 2012
• 卷：1821
• 期：4
• 页码：618-626
• 文件大小：913 K

摘要

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-尾-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.