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Biological Significance of Essential Fatty Acids/Prostanoids/Lipoxygenase-Derived Monohydroxy Fatty Acids in the Skin  

Ziboh, Vincent-A. (Department of Dermatology, University of California Davis)
Cho, Yunhi (Department of Dermatology, University of California Davis)
Mani, Indu (Department of Dermatology, University of California Davis)
Xi, Side (Department of Dermatology, University of California Davis)
Publication Information
Archives of Pharmacal Research / v.25, no.6, 2002 , pp. 747-758 More about this Journal
Abstract
The skin displays a highly active metabolism of polyunsaturated fatty acids (PUFA). Dietary deficiency of linoleic acid (LA), an 18-carbon (n-6) PUFA, results in characteristic scaly skin disorder and excessive epidermal water loss. Although arachidonic acid (AA), a 20-carbon (n6) PUFA, is metabolized via cyclooxygenase pathway into predominantly prostaglandin $E_2(PGE_2)$ and $PGF_{2{\alpha}}$, the metabolism of AA via the 15-lipoxygenase (15-LOX) pathway, which is very active in skin epidermis and catalyzes the transformation of M into predominantly 15S-hydroxyeicosatetraenoic acid (15S-HETE). Additionally, the 15-LOX also metabolizes the 18-carbon LA into 13S-hydroxyoctadecadienoic acid (13S-HODE), respectively. Interestingly, 15-LOX catalyzes the transformation of $dihomo-{\gamma}-linolenic$ acid (DGLA), derived from dietary gamma-linolenic acid, to 15S-hydroxyeicosatrienoic acid (15S-HETrE). These monohydroxy fatty acids are incorporated into the membrane inositol phospholipids which undergo hydrolytic cleavage to yield substituted-diacylglycerols such as 13S-HODE-DAG from 13S-HODE and 15S-HETrE-DAG from 15S-HETrE. These substituted-monohydroxy fatty acids seemingly exert anti-inflammatory/antiproliferative effects via the modulation of selective protein kinase C as well as on the upstream/down-stream nuclear MAP-kinase/AP-1/apoptotic signaling events.
Keywords
Fatty acids; Prostanoids; Lipoxygenase; Epidermal proliferation; 15S-HETE; 15S-HETrE; PUFA; Linoleic acid; 13S-HODE; Cell signal; PKC; Skin; Cox-2
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