13-Hydroxyoctadecadienoic acid reverses epidermal hyperproliferation via selective inhibition of protein kinase C-beta activity.
13-Hydroxyoctadecadienoic acid (13-HODE) is a major lipoxygenase metabolite of linoleic acid in epidermis. Employing a docosahexaenoic acid (22:6n-3) induced model of hyperproliferative guinea pig epidermis, we demonstrated reversal of hyperproliferation by topical 13-HODE. To delineate a possible mechanism for 13-HODE effect, we demonstrated that topical 13-HODE was incorporated into 13-HODE-containing diacylglycerol (13HODE-DAG). This novel substituted-DAG which was markedly depleted in the hyperproliferative skin paralleled the increased activities of PKC-alpha and beta. Replenishment of the hyperproliferative epidermis with topical 13-HODE resulted in the accumulation of tissue 13HODE-DAG and the selective suppression of PKC-beta activity. These data taken together suggest that the generation of putative 13-HODE-DAG and the selective suppression of PKC-beta isozyme activity may play a role in modulating epidermal hyperproliferation.
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Department of Dermatology, University of California, Davis 95616.
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D000287:Administration, Topical; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004075:Diglycerides / Q000378:metabolism; D000078404:Epidermal Cells; D006131:Growth Inhibitors; D006168:Guinea Pigs; D007527:Isoenzymes; D008041:Linoleic Acids / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D004075:Diglycerides; D006131:Growth Inhibitors; D007527:Isoenzymes; D008041:Linoleic Acids; C024348:13-hydroxy-9,11-octadecadienoic acid; D004247:DNA; D011493:Protein Kinase C