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 fatty acid (FA) composition on inositol phosphate (InsP) release by a human colon tumor cell line. Cells were supplemented for five days in culture with 0, 10, 30, or 100 microM sodium stearate (18:0), linoleate [18:2(omega-6)], or linolineate [18:3(omega-3)]. These FAs were supplied as a complex with FA-free bovine serum albumin. InsP release was examined in these cells with or without stimulation with deoxycholic acid (DCA) after they were labeled with [3H]myoinositol. FA enrichment was found to influence inositol incorporation into membrane lipids. Although 18:0 had no effect, 18:2(omega-6) decreased the incorporation. On the other hand, 18:3(omega-3) increased the incorporation of inositol compared with the cells supplemented with the other FAs, but they were not different from control. Basal release of total InsP was elevated only with supplementation of 10 and 30 microM 18:3(omega-3). FA supplementation with 18:0 at 30 microM and 18:2 at 30 and 100 microM resulted in downregulation of bsal release of InsP. Enrichment of HT-29 cell membranes with polyunsaturated FAs resulted in a significant increase in stimulated release of InsP, but this was not seen with saturated FA supplementation. At 10 microM supplementation, 18:2 had the greatest effect on stimulated InsP release. This effect of 18:2 disappeared at 30 microM. However, the increase in the stimulated InsP release caused by 18:3 occurred at 10 and 30 microM. DCA-stimulated release of InsP was not downregulated by any FA supplementation. This study showed that enrichment of the membranes with polyunsaturated FAs increases the response of the phosphatidylinositol cycle to DCA stimulation. In addition, enrichment with 18:3(omega-3) increases the basal turnover of InsP. It is concluded that alteration of membrane FAs has a profound effect on the phosphatidylinositol cycle.
Nutrition Program, University at Buffalo, NY 14214.
A B
AB
Awad
C S
CS
Fink
P J
PJ
Horvath
D003110:Colonic Neoplasms / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis* / Q000494:pharmacology; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D008563:Membrane Lipids / Q000032:analysis* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005227:Fatty Acids; D007295:Inositol Phosphates; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D007294:Inositol