Effects of 12-HETE on renal tubular epithelial cells

The interaction of 12-HETE with MDCK cells was investigated to determine whether this lipoxygenase product might influence tubular epithelial function. MDCK cells took up 12-HETE from both the luminal and interstitial surfaces. Much of the 12-HETE was incorporated into phospholipids but, unlike arachidonic acid, there was no specificity for the sn-2 position. 12-HETE was incorporated without chemical modification, suggesting that it might perturb tight packing in the lipid bilayer. 12-HETE uptake was reduced by the presence of arachidonic acid, but not by oleic acid. 12-HETE was removed from the cell lipids more rapidly than arachidonic acid and it was released into the medium in the form of both more and less polar metabolites. When MDCK cells were incubated with 12-HETE, their capacity to produce prostaglandin E2 was reduced. Since 12-HETE enters epithelial phospholipids and is converted to metabolic products and reduces prostaglandin production, it apparently has the capacity to modulate renal function if it is released in the proximity of the tubular epithelium.