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We have investigated the extent to which modifications in the essential fatty acid content of mammalian cells can affect prostaglandin production. Swiss mouse 3T3 cells stimulated with the calcium ionophore A23187 produced 1.7 to 7 times more prostaglandin E(2) (PGE(2)) when the cultures were supplemented with linoleic acid. Increases in PGE(2) production as a result of linoleic acid supplementation occurred under all culture conditions except during the first 24 hr after attachment, when prostaglandin production was very high. Arachidonic acid supplementation produced a similar enhancement in the capacity of the cells to produce PGE(2), but no appreciable increase occurred when the cultures were supplemented with oleic acid. The phospholipids of the cells exposed to the linoleate-enriched medium contained 4 times more arachidonic acid and twice as much linoleic acid as compared with the corresponding controls. The choline phosphoglycerides were most highly enriched in arachidonic acid, but 2- to 3-fold increases also occurred in the inositol and ethanolamine phosphoglycerides. When cultures initially enriched with linoleic acid were transferred to an unsupplemented medium, the fatty acid composition as well as the capacity of the cells to produce PGE(2) reverted almost to control values. The amount of exogenous arachidonic acid converted to PGE(2) as measured by radioimmunoassay also was greater when the cells were enriched with linoleic acid. Studies with radioactive arachidonic acid indicated that the distribution of prostaglandin metabolites was not affected appreciably by linoleic acid enrichment. These findings suggest that at least two factors contribute to the increased capacity of the cultures supplemented with linoleate to produce PGE(2). One is enrichment of the phospholipid substrate pools with arachidonic acid. The other is an increased ability of the cells to synthesize PGE(2) from unesterified arachidonic acid, perhaps because the prostaglandin-forming enzymes are more active.-Denning, G. M., P. H. Figard, and A. A. Spector. Effect of fatty acid modification on prostaglandin production by cultured 3T3 cells.
G M Denning, and
P H Figard, and
A A Spector
May 1980,
The Journal of clinical investigation,
G M Denning, and
P H Figard, and
A A Spector
November 1981,
Prostaglandins,
G M Denning, and
P H Figard, and
A A Spector
September 1982,
Cancer research,
G M Denning, and
P H Figard, and
A A Spector
November 1982,
Biochimica et biophysica acta,
G M Denning, and
P H Figard, and
A A Spector
November 1987,
Prostaglandins, leukotrienes, and medicine,
G M Denning, and
P H Figard, and
A A Spector
January 1979,
Agents and actions. Supplements,
G M Denning, and
P H Figard, and
A A Spector
February 1981,
Archives internationales de pharmacodynamie et de therapie,
G M Denning, and
P H Figard, and
A A Spector
February 1996,
Biochimica et biophysica acta,
G M Denning, and
P H Figard, and
A A Spector
April 1995,
Nihon Sanka Fujinka Gakkai zasshi,
G M Denning, and
P H Figard, and
A A Spector
January 1982,
Arteriosclerosis (Dallas, Tex.),
