Diacylglycerol-containing oleic acid induces increases in [Ca(2+)](i) via TRPC3/6 channels in human T-cells.
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 [Ca(2+)](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 [Ca(2+)](i) in these cells. POG-evoked increases in [Ca(2+)](i) were not due to its metabolites. Furthermore, POG-induced increases in [Ca(2+)](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 [Ca(2+)](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.
Área de Nutrición y Bromatología, Facultad de Ciencias, Universidad de Burgos, Pl. Misael Bañuelos s/n, 09001 Burgos, Spain.
Celia
C
Carrillo
Aziz
A
Hichami
Pierre
P
Andreoletti
Mustapha
M
Cherkaoui-Malki
María
M
del Mar Cavia
Souleymane
S
Abdoul-Azize
Sara R
SR
Alonso-Torre
Naim Akhtar
NA
Khan
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D019169:Jurkat Cells; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D000074287:TRPC6 Cation Channel; D047392:beta-Cyclodextrins / Q000494:pharmacology
D004075:Diglycerides; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C083975:1-palmitoyl-2-oleoyl-sn-glycerol; C084199:1-stearoyl-2-oleoyl-sn-glycerol; C075809:1-stearoyl-2-arachidonoylglycerol; D002118:Calcium