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Journal of Lipid Research, Vol. 14, 377-384, July 1973
Copyright © 1973 by Lipid Research, Inc.

Biosynthesis of prostaglandin E₂ in human skin: subcellular localization and inhibition by unsaturated fatty acids and anti-inflammatory drugs

Vincent A. Ziboh

Departments of Dermatology and Biochemistry, University of Miami School of Medicine, Miami, Florida 33152

The biosynthesis of prostaglandin E₂ (PGE₂) from [1-¹⁴C]arachidonic acid has been demonstrated in homogenates and subcellular fractions of human epidermis. This biosynthetic capacity is localized in the microsomal fraction, indicating the presence of an active prostaglandin synthetase system associated with membranes of the skin. The incorporation of ¹⁴C from [1-¹⁴C]arachidonic acid into PGE₂ by the microsomal fraction was enhanced by EDTA. This apparent increase in ¹⁴C incorporation into PGE₂ in the presence of EDTA could be due at least in part to its chelating properties of removing the divalent cations in the homogenate that enhance the selective formation of PGF₂ and the suppression of the activity of epidermal phospholipase A, which causes the release of nonradioactive fatty acid precursors from endogenous phospholipids. This study has also demonstrated that the formation of PGE₂ from arachidonic acid by the microsomal fraction from human skin could be inhibited by polyunsaturated fatty acids, suggesting a possible regulatory role of fatty acids released from endogenous phospholipids on prostaglandin synthesis in this tissue. The inhibitory effects of some anti-inflammatory drugs on skin microsomal prostaglandin synthetase were also demonstrated in these studies. Results from these studies indicate that the skin is therefore a useful tissue for the study of mechanisms of prostaglandin biosynthesis and the mode of action of various anti-inflammatory drugs.

Supplementary key words essential fatty acid • thin-layer chromatography • polyunsaturated fatty acids • eicosatrienoic acid • triamcinolone acetonide • dexamethasone

Submitted on August 29, 1972
Accepted on January 31, 1973

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