13-Hydroxyoctadecadienoic acid reverses epidermal hyperproliferation via selective inhibition of protein kinase C-beta activity

Cho, Y.; Ziboh, V.A.

Biochemical and Biophysical Research Communications 201(1): 257-265

1994


ISSN/ISBN: 0006-291X
PMID: 8198583
Document Number: 430336
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 (13-HODE-DAG). This novel substituted-DAG which was markedly depleted in the hyperproliferative skin paralled the increased activities of PKC-alpha and beta. Replenishment of the hyperproliferative epidermis with topical 13-HODE resulted in the accumulation of tissue 13-HODE-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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