ALTERATION OF MEMBRANE FATTY-ACID COMPOSITION AND INOSITOL PHOSPHATE-METABOLISM IN HT-29 HUMAN COLON CANCER-CELLS

The present study was designed to investigate the role of membrane fat ty acid (FA) composition on inositol phosphate (InsP) release by a hum an colon tumor cell line. Cells were supplemented for five days in cul ture with 0, 10, 30, or 100 muM sodium stearate (18:0), linoleate [18: 2(omega-6)], or linolineate [18:3(omega-3)]. These FAs were supplied a s a complex with FA-free bovine serum albumin. InsP release was examin ed in these cells with or without stimulation with deoxycholic acid (D CA) after they were labeled with [H-3]myoinositol. FA enrichment was f ound to influence inositol incorporation into membrane lipids. Althoug h 18:0 had no effect, 18:2(omega-6) decreased the incorporation. On th e other hand, 18:3(omega-3) increased the incorporation of inositol co mpared with the cells supplemented with the other FAs, but they were n ot different from control. Basal release of total InsP was elevated on ly with supplementation of 10 and 30 muM 18:3(omega-3). FA supplementa tion with 18:0 at 30 muM and 18:2 at 30 and 100 muM resulted in downre gulation of basal release of InsP. Enrichment of HT-29 cell membranes with polyunsaturated FAs resulted in a significant increase in stimula ted release of InsP, but this was not seen with saturated FA supplemen tation. At 10 muM supplementation, 18:2 had the greatest effect on sti mulated InsP release. This effect of 18:2 disappeared at 30 muM. Howev er, the increase in the stimulated InsP release caused by 18:3 occurre d at 10 and 30 muM. DCA-stimulated release of InsP was not downregulat ed by any FA supplementation. This study showed that enrichment of the membranes with polyunsaturated FAs increases the response of the phos phatidylinositol cycle to DCA stimulation. In addition, enrichment wit h 18:3(omega-3) increases the basal turnover of InsP. It is concluded that alteration of membrane FAs has a profound effect on the phosphati dylinositol cycle.