Biological significance of essential fatty acids/prostanoids/lipoxygenase-derived monohydroxy fatty acids in the skin.
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 PGF2alpha, 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-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.
Ziboh
Vincent A
VA
Department of Dermatology, University of California Davis, Davis, CA 95616, USA. vaziboh@ucdavis.edu
Cho
Yunhi
Y
Mani
Indu
I
Xi
Side
S
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005228:Fatty Acids, Essential / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008084:Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D011453:Prostaglandins / Q000737:chemistry / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism*
D005228:Fatty Acids, Essential; D011453:Prostaglandins; D008084:Lipoxygenase