BIOGENESIS AND METABOLIC-FATE OF DOCOSAHEXAENOIC AND ARACHIDONIC ACIDS IN RAT UTERINE STROMAL CELLS IN CULTURE

To gain some insight into the mechanisms involved in the opposing effe cts of arachidonic acid and docosahexaenoic acid on the growth of rat uterine stromal cells (U-III cells), the dynamics of the uptake, conve rsion, and incorporation of labeled 18:2(n-6), 18:3(n-3), 20:4(n-6), 2 0:5(n-3), and 22:6(n-3) into lipid pools and phospholipid subclasses w ere examined. A very active and time-dependent conversion of [C-14]18: 3(n-3) to higher homologs was observed; 64.7 +/- 0.7 and 11.5 +/- 0.4% of the [C-14] radioactivity incorporated in cellular lipids were reco vered as 22:5(n-3) and 22:6(n-3) after 72 h incubation, respectively. The distribution of labeled fatty acids obtained after 72 h incubation with [H-3]20:5(n-3) was not significantly different from that observe d with 18:3(n-3). Arachidonic acid was the major fatty acid formed fro m [C-14]18:2(n-6) and only trace amounts of 22:5(n-6) were detected. W hen cells were incubated for 72 h with 20:4(n-6), more than 75% of the radioactivity was recovered as arachidonate and slightly higher amoun ts of 22:4(n-6) and 22:5(n-6) were formed compared to those obtained a fter incubation with 18:2(n-6). Using both [C-14]- and [H-3]22:6(n-3), no significant retroconversion of labeled 22:6(n-3) occurred in the c ells. More than 90% of labeled 20:4(n-6) and 22:6(n-3) taken up by the cells were esterified into phospholipids, but significant differences in their distribution among phospholipid classes and subclasses were observed. Docosahexaenoic acid was more rapidly and efficiently incorp orated into phosphatidylethanolamine than 20:4(n-6) and was principall y recovered in plasmalogens. Arachidonic acid was mainly incorporated in the diacyl subclasses of phosphatidylcholine and phosphatidylethano lamine and in phosphatidylinositol. The divergent distribution profile s of these two fatty acids within the phospholipid compartments provid e some information for the mechanisms of their opposite effects on U-I II cell growth. (C) 1996 Academic Press, Inc.