Polyunsaturated free fatty acids stimulate an increase in cytosolic Ca2+ by mobilizing the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in T cells through a mechanism independent of phosphoinositide turnover.
Polyunsaturated free fatty acids (PUFAs) of both w-3 and w-6 series, induce a rapid increase of cytosolic free Ca2+ concentration ([Ca2+]i) in a leukemic T-cell line (JURKAT), measured by the fluorescent indicator fura-2. The early increase in [Ca2+]i was transient, falling to a sustained level which returned to base line after 10-15 min. In Ca2+-free medium, PUFAs still caused an early increase in [Ca2+]i but rapidly returned to basal. Depletion of endoplasmic reticular Ca2+ pool by addition of OKT3 (antibodies to CD3 of the T3-antigen receptor complex) to JURKAT cells (in Ca2+-free medium) abolished the PUFAs-mediated [Ca2+]i increase and vice versa. By using saponin-permeabilized JURKAT cells, the intracellular free Ca2+ released by PUFAs was found to be the non-mitochondrial, ATP-dependent sequestered Ca2+ pool which is sensitive to inositol 1,4,5-trisphosphate. However, PUFAs do not induce any apparent increase in inositol phosphates in JURKAT cells. No Ca2+ influx was detected in JURKAT cells when stimulated with PUFAs. A correlation was observed between both the carbon chain length and the number of double bonds with the ability to mobilize cytosolic free [Ca2+]i in the w-3 PUFAs. These results demonstrate that PUFAs stimulate the release of Ca2+ from the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in the endoplasmic reticulum of JURKAT cells via a mechanism independent of inositol lipid hydrolysis.
Chow
S C
SC
Department of Immunology, Karolinska Institute, Stockholm, Sweden.
Jondal
M
M
D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003600:Cytosol / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D001572:Benzofurans; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D010716:Phosphatidylinositols; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D016257:Fura-2