Abstract
PUFAs are important constituents of membrane glycerophospholipids. However, changes in the capacities to incorporate and metabolize PUFAs when cells enter the cell cycle have not been thoroughly studied. In this study, differences in the incorporation and metabolism of exogenous PUFAs in resting and proliferating primary human T-cells and in the Jurkat cell line were measured. Overall, proliferating T-cells and Jurkat cells had a greater capacity to incorporate and elongate exogenous 18- and 20-carbon PUFAs compared with resting T-cells. Proliferating T-cells and Jurkat cells also showed a greater capacity to desaturate 18-carbon PUFA substrates. Consistent with these observations, a significant increase in the expression of fatty acid desaturase (FADS) 1, FADS2, and elongation of very long chain fatty acids protein (ELOVL) 5 was measured in proliferating T-cells compared with resting T-cells. No quantifiable ELOVL2 was measured. Knockdown of ELOVL5 in T-cells and Jurkat cells significantly affected cellular monounsaturated and PUFA profiles and strongly impaired the elongation of 18- and 20-carbon PUFAs. In conclusion, the induction of proliferation in human T-cells is associated with a significant increase in the capacity to take up and metabolize exogenous PUFAs, and ELOVL5 is responsible for the elongation of 18- and 20-carbon PUFAs in these cells.
Highlights
PUFAs are important constituents of membrane glycerophospholipids
The accumulation of linoleic acid (LA) compared with nonsupplemented controls that was measured in proliferating T-cells and in Jurkat cells was accompanied by an augmentation of cellular 20:2n-6 content; in Jurkat cells there was an increase in 18:3n-6 and 20:3n-6 (Fig. 2B, C).When cells were incubated with 18:3n-6 (GLA), only the accumulation of a small quantity of -linolenic acid (GLA) was measured in resting T-cells that was different from controls (Fig. 2A)
The expression of the T-cell activation markers, CD25 and CD69, was not affected by ELOVL5 knockdown in stimulated primary T-cells. These results indicate that ELOVL5 expression does not appear to be required for the maintenance of cell proliferation and viability or the activation of primary T-cells under these culture conditions. In many cancers both de novo saturated fatty acid (SFA) biosynthesis and stearoyl-CoA desaturase 1 (SCD1) ( 9-desaturase) expression are significantly increased and likely to generate a supply of SFAs and MUFAs required for membrane biogenesis to support cell proliferation [1,2,3,4,5,6, 31]
Summary
PUFAs are important constituents of membrane glycerophospholipids. changes in the capacities to incorporate and metabolize PUFAs when cells enter the cell cycle have not been thoroughly studied. Proliferating T-cells and Jurkat cells showed a greater capacity to desaturate 18-carbon PUFA substrates Consistent with these observations, a significant increase in the expression of fatty acid desaturase (FADS) 1, FADS2, and elongation of very long chain fatty acids protein (ELOVL) 5 was measured in proliferating T-cells compared with resting T-cells. We previously showed that the expression of many enzymes involved in PUFA-GPL remodeling such as acyl-CoA synthases, lysophospholipid acyl-CoA transferases, and phospholipases A2 are modified when cells are stimulated to proliferate [9] Such PUFAs that are not products of de novo FA biosynthesis are important structural components of cellular membranes [10,11,12,13] that perform signaling functions and serve as ligands for nuclear receptors as well as precursors to lipid mediators such as the eicosanoids [14,15,16,17,18]. These 18-carbon PUFAs can undergo a series of elongation and desaturation reactions to generate longer-chain, more unsaturated
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