Journal of Lipid Research, Vol 35, 913-921, Copyright © 1994 by Lipid Research, Inc.

ARTICLES

Expression of protein kinase C isozymes in guinea pig epidermis: selective inhibition of PKC-beta activity by 13-hydroxyoctadecadienoic acid-containing diacylglycerol

Y Cho and VA Ziboh
Department of Dermatology, School of Medicine, University of California, Davis 95616.

Prompted by the reversal of skin hyperproliferation to normal by 13- hydroxyoctadecadienoic acid (13-HODE), a 15-lipoxygenase metabolite of linoleic acid, we investigated a possible mechanism for this antiproliferative action. To address this we first demonstrated that 13- HODE is incorporated into epidermal phosphatidyl 4,5-bisphosphate (PtdIns4,5-P2) and released as 13-HODE-containing diacylglycerol by epidermal phospholipase C. Secondly, we tested the possibility whether this putative 13-HODE-containing DAG (13HODE-DAG) could exert a modulatory effect on epidermal protein kinase C (PKC) activity which previously has been associated with skin hyperproliferation. Unlabeled 13HODE-DAG was generated from 13-HODE-containing phosphatidylcholine after phospholipase C hydrolytic cleavage. The effects of the 13HODE- DAG were determined on: i) total epidermal PKC activity; ii) diolein- activated PKC activity; and iii) the two identified epidermal PKC- isozymes (PKC-beta and PKC-alpha). Our data revealed over a twofold activation of total basal PKC activity by diolein. In contrast, replacement of diolein (1,2-dioleoylglycerol) with 13HODE-DAG (1- palmitoyl,2-13HODE-glycerol) in the incubation mixture exerted no effect on total basal PKC activity. In an another experiment, 13HODE- DAG inhibited diolein-activated PKC activity in a dose-dependent manner. To determine whether the effects of 13HODE-DAG are selective, we tested its effects on DEAE-Sephacel-purified and Western blot- confirmed PKC isozymes. Our data revealed that 13HODE-DAG selectively inhibited the activity of PKC-beta isozyme, while exerting negligible effect on the PKC-alpha isozyme. This selective inhibitory effect of 13HODE-DAG on a major epidermal PKC isozyme activity suggests that 13HODE-containing DAG seemingly can modulate epidermal PKC activity, which purportedly is associated with epidermal hyperproliferation.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. A Ziboh, C. C Miller, and Y. Cho Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites1 Am. J. Clinical Nutrition, January 1, 2000; 71(1): 361S - 366S. [Abstract] [Full Text] [PDF]

				D. Hwang and S. H Rhee Receptor-mediated signaling pathways: potential targets of modulation by dietary fatty acids Am. J. Clinical Nutrition, October 1, 1999; 70(4): 545 - 556. [Abstract] [Full Text] [PDF]

				S. E. Alpert, R. W. Walenga, A. Mandal, N. Bourbon, and M. Kester 15-HETE-substituted diglycerides selectively regulate PKC isotypes in human tracheal epithelial cells Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L457 - L464. [Abstract] [Full Text] [PDF]

				X. Fang, T. L. Kaduce, and A. A. Spector 13-(S)-Hydroxyoctadecadienoic acid (13-HODE) incorporation and conversion to novel products by endothelial cells J. Lipid Res., April 1, 1999; 40(4): 699 - 707. [Abstract] [Full Text]

				S. P. Jayawickreme, T. Gray, P. Nettesheim, and T. Eling Regulation of 15-lipoxygenase expression and mucus secretion by IL-4 in human bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, April 1, 1999; 276(4): L596 - L603. [Abstract] [Full Text] [PDF]