Biological significance of essential fatty acids/prostanoids/ lipoxygenase-derived monohydroxy fatty acids in the skin

• Published in: Archives of pharmacal research Vol. 25; no. 6; pp. 747 - 758
• Main Authors: Ziboh, Vincent A, Cho, Yunhi, Mani, Indu, Xi, Side
• Format: Journal Article
• Language: English
• Published: Korea (South) Pharmaceutical Society of Korea 01.12.2002
• Subjects: Animals; arachidonic acid; Cell Differentiation - physiology; fatty acids; Fatty Acids, Essential - chemistry; Fatty Acids, Essential - metabolism; gamma-linolenic acid; Humans; linoleic acid; Lipoxygenase - chemistry; Lipoxygenase - metabolism; metabolism; myo-inositol; phospholipids; polyunsaturated fatty acids; prostaglandin synthase; prostaglandins; Prostaglandins - chemistry; Prostaglandins - metabolism; protein kinase C; Skin - cytology; Skin - metabolism; skin diseases
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/bf02976988

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 (n-6) PUFA, is metabolized via cyclooxygenase pathway into predominantly prostaglandin E₂ (PGE₂) and PGF₂α, the metabolism of AA via the 15-lipoxygenase (15-LOX) pathway, which is very active in skin epidermis and catalyzes the transformation of AA 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-γ-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 hydro-lytic 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.