J Korean Med Sci.  2010 Jun;25(6):980-983. 10.3346/jkms.2010.25.6.980.

Skin Aging and Photoaging Alter Fatty Acids Composition, Including 11,14,17-eicosatrienoic Acid, in the Epidermis of Human Skin

Affiliations
  • 1Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous Aging Research, Clinical Research Institute, Seoul National University Hospital, Institute of Dermatological Science, Seoul National University, Seoul, Korea

Abstract

We investigated the alterations of major fatty acid components in epidermis by natural aging and photoaging processes, and by acute ultraviolet (UV) irradiation in human skin. Interestingly, we found that 11,14,17-eicosatrienoic acid (ETA), which is one of the omega-3 polyunsaturated acids, was significantly increased in photoaged human epidermis in vivo and also in the acutely UV-irradiated human skin in vivo, while it was significantly decreased in intrinsically aged human epidermis. The increased ETA content in the epidermis of photoaged human skin and acute UV-irradiated human skin is associated with enhanced expression of human elongase 1 and calcium-independent phophodiesterase A2. We demonstrated that ETA inhibited matrix metalloproteinase (MMP)-1 expression after UV-irradiation, and that inhibition of ETA synthesis using EPTC and NA-TCA, which are elongase inhibitors, increased MMP-1 expression. Therefore, our results suggest that the UV increases the ETA levels, which may have a photoprotective effect in the human skin.

Keyword

Ultraviolet Rays; Fatty Acids, Nonesterified; Fatty Acids, Omega-3; 11,14,17-eicosatrienoic acid; Phospholipases A2, Calcium-Independent; Human Elongase 1

Figure

  • Fig. 1 The changes of free fatty acid (FFA) composition in the epidermis of human skin. (A) The changes of FFA composition in aged epidermis. Young human (mean age 26.5 yr; age range 21-33 yr, n=4) buttock skin and aged human (mean age 72.7 yr; age range 70-75 yr, n=4) buttock skin were obtained by punch biopsy. Total lipids were extracted with chroloform/methanol/water (1:2:0.8, v/v/v). Lipid extracts were analyzed by typical gas chromatography (GC). *P<0.05, †P<0.01, C16:0-palmitic acid (PA), C16:1-palmitoleic acid (PtA), C18:0-stearic acid (SA), C18:1n9-oleic acid (OA), 18:2n6-linoleic acid (LA), C20:3n3-(All-cis)-11,14,17-eicosatrienoic acid (ETA). (B) The change of FFA composition in photoaged epidermis. Aged human (mean age 72.7 yr; age range 70-75 yr, n=5) buttock/forearm skin were obtained by punch biopsy. Total lipids were extracted with chroloform/methanol/water (1:2:0.8, v/v/v). Lipid extracts were analyzed by typical gas chromatography (GC). †P<0.01, C16:0-palmitic acid (PA), C16:1-palmitoleic acid (PtA), C18:0-stearic acid (SA), C18:1n9-oleic acid (OA), 18:2n6-linoleic acid (LA), C20:3n3-(All-cis)-11,14,17-eicosatrienoic acid (ETA). (C) The change of FFA composition in acutely UV-irradiated buttock epidermis. Young human (mean age 26.5 yr; age range 21-33 yr, n=4) buttock skin was obtained by punch biopsy at the indicated time points after UV irradiation (2 MED). Total lipids were extracted with chroloform/methanol/water (1:2:0.8, v/v/v). Lipid extracts were analyzed by typical gas chromatography (GC). *P<0.05, C16:0-palmitic acid (PA), C16:1-palmitoleic acid (PtA), C18:0-stearic acid (SA), C18:1n9-oleic acid (OA), 18:2n6-linoleic acid (LA), C20:3n3-(All-cis)-11,14,17-eicosatrienoic acid (ETA).

  • Fig. 2 The expressions of genes involved in ETA production and the effect of ETA on MMP-1 expression. (A) The expression of HELO1 involved in the elongation of fatty acids. (Left) Aged human (mean age 72.7 yr; age range 70-75 yr) buttock/forearm skin were obtained by punch biopsy. Levels of HELO1 were determined by real-time PCR (n=4). *P<0.05. (Right) Normal human keratinocytes were incubated for 24 hr after UV irradiation (100 mJ/cm2). Levels of iPLA2 were determined by real-time PCR (n=3). *P<0.05. (B) The expression of iPLA2 involved in the release of ETA from phospholipids. (Left) Aged human (mean age 72.7 yr; age range 70-75 yr) buttock/forearm skin were obtained by punch biopsy. Levels of iPLA2 were determined by real-time PCR (n=4). *P<0.05.(Right) Normal human keratinocytes were incubated for 24 hr after UV irradiation (100 mJ/cm2). Levels of iPLA2 were determined by real-time PCR (n=3). *P<0.05. (C) The effect of ETA on UV-induced MMP-1 expression. Normal human keratinocytes were incubated with ETA for 24 hr after UV irradiation (100 mJ/cm2). Levels of MMP-1 were determined by Western blots. (n=3). (D) Normal human keratinocytes were incubated with each elongase inhibitor for 24 hr. Levels of MMP-1 were determined by real-time PCR (n=3). *P<0.05.


Reference

1. Jenkins G. Molecular mechanisms of skin ageing. Mech Ageing Dev. 2002. 123:801–810.
2. Fisher GJ, Kang S, Varani J, Bata-Csorgo Z, Wan Y, Datta S, Voorhees JJ. Mechanisms of photoaging and chronological skin aging. Arch Dermatol. 2002. 138:1462–1470.
3. Trommer H, Wagner J, Graener H, Neubert RH. The examination of skin lipid model systems stressed by ultraviolet irradiation in the presence of transition metal ions. Eur J Pharm Biopharm. 2001. 51:207–214.
4. Hansen HS, Jensen B. Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and alpha-linolenate. Biochim Biophys Acta. 1985. 834:357–363.
5. Jump DB. Fatty acid regulation of gene transcription. Crit Rev Clin Lab Sci. 2004. 41:41–78.
6. Siddiqui RA, Harvey KA, Zaloga GP. Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health. J Nutr Biochem. 2008. 19:417–437.
7. Jakobsson A, Westerberg R, Jacobsson A. Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog Lipid Res. 2006. 45:237–249.
8. Leonard AE, Bobik EG, Dorado J, Kroeger PE, Chuang LT, Thurmond JM, Parker-Barnes JM, Das T, Huang YS, Mukerji P. Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids. Biochem J. 2000. 350(Pt 3):765–770.
9. Strokin M, Sergeeva M, Reiser G. Docosahexaenoic acid and arachidonic acid release in rat brain astrocytes is mediated by two separate isoforms of phospholipase A2 and is differently regulated by cyclic AMP and Ca2+. Br J Pharmacol. 2003. 139:1014–1022.
10. Daviglus ML, Stamler J, Orencia AJ, Dyer AR, Liu K, Greenland P, Walsh MK, Morris D, Shekelle RB. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997. 336:1046–1053.
11. Kushi L, Giovannucci E. Dietary fat and cancer. Am J Med. 2002. 113:Suppl 9B. 63S–70S.
12. Horrobin DF, Bennett CN. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes. Prostaglandins Leukot Essent Fatty Acids. 1999. 60:217–234.
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr