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필수지방산 결핍이 유도된 기니피그에서 보라지유와 홍화유 섭취의 표피 과증식 억제 및 세라마이드 대사에 미치는 효과 비교

Comparative effect of dietary borage oil and safflower oil on anti-proliferation and ceramide metabolism in the epidermis of essential fatty acid deficient guinea pigs

  • 이세령 (경희대학교 동서의학대학원 의학영양학과) ;
  • 조윤희 (경희대학교 동서의학대학원 의학영양학과)
  • Lee, Se Ryung (Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Cho, Yunhi (Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University)
  • 투고 : 2015.06.10
  • 심사 : 2015.07.24
  • 발행 : 2015.08.31

초록

본 연구에서는 기니피그에 8주간 필수지방산 결핍 식이 공급에 의해 표피 과증식을 유도한 후 계속된 2주간의 보라지유 또는 홍화유 식이 공급에 의한 과증식 억제 및 Cer, GlcCer, SM의 표피 함량 및 세라마이드 대사 관련 효소들의 단백질 발현 변화를 정상대조군인 BO군 및 필수지방산 결핍 군인 HCO군과 비교하였으며 그 결과는 다음과 같다. 1. 8주간의 필수지방산 결핍 식이 공급 후 계속된 2주간의 보라지유 식이 공급 (HCO + BO군)은 2주간의 홍화유 식이 공급에 (HCO + SO군) 비해 더욱 현저히 표피 과증식을 억제하였다. 2. 10주간 필수지방산 결핍식이를 공급한 HCO군은 정상대조군인 BO군에 비해 Cer의 총 함량 및 Cer1/2/5/6/7, GlcCer-A/B의 함량이 유의적으로 감소되었다. HCO + BO군의 Cer과 GlcCer의 총 함량 및 Cer1/2, GlcCer-A/B, SM1의 함량은 HCO군에 비해 유의적으로 증가한 반면 HCO + SO군의 이들 함량은 HCO군과 유사하였다. GlcCer-C/D, SM의 총 함량 및 SM 2/3의 함량은 군간 변화가 없었다. 3. HCO군에서는 GCase 발현이 감소한 반면 HCO + BO군에서는 현저히 증가하였다. HCO + SO군의 aSMase의 단백질 발현이 HCO군에 비해 유의적으로 증가하였으나 aCDase의 발현 또한 다른 군에 비해 현저히 증가하였다. HCO + BO군과 HCO + SO군 모두 SPT의 단백질 발현이 HCO군에 비해 유의적으로 증가하였다. 결론적으로 표피 과증식이 유도된 기니피그에 보라지유 식이 공급은 GlcCer-A/B을 포함하는 GlcCer 총 함량, SM1 및 GCase의 발현 증가와 더불어 Cer1/2를 포함하는 Cer 총 함량을 증가시켜 궁극적으로 표피 과증식을 현저히 억제하였다.

Purpose: Borage oil (BO) and safflower oil (SO) are efficacious in reversing epidermal hyperproliferation, which is caused by the disruption of epidermal barrier. In this study, we compared the antiproliferative effect of dietary BO and SO. Altered metabolism of ceramide (Cer), the major lipid of epidermal barrier, was further determined by measurement of epidermal levels of individual Cer, glucosylceramide (GlcCer), and sphingomyelin (SM) species, and protein expression of Cer metabolizing enzymes. Methods: Epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut diet (HCO) for 8 weeks. Subsequently, animals were fed diets of either BO (group HCO + BO) or SO (group HCO + SO) for 2 weeks. As controls, animals were fed BO (group BO) or HCO (group HCO) diets for 10 weeks. Results: Epidermal hyperproliferation was reversed in groups HCO + BO (67.6% of group HCO) and HCO + SO (84.5% of group HCO). Epidermal levels of Cer1/2, GlcCer-A/B, and ${\beta}$-glucocerebrosidase (GCase), an enzyme of GlcCer hydrolysis for Cer generation, were higher in group HCO + BO than in group HCO, and increased to levels similar to those of group BO. In addition, epidermal levels of SM1, serine palmitoyltransferase (SPT), and acidic sphingomyelinase (aSMase), enzymes of de novo Cer synthesis and SM hydrolysis for Cer generation, but not of Cer3-7, were higher in group HCO + BO than in group HCO. Despite an increase of SPT and aSMase in group HCO + SO to levels higher than in group HCO, epidermal levels of Cer1-7, GlcCer-A/B, and GCase were similar in these two groups. Notably, acidic ceramidase, an enzyme of Cer degradation, was highly expressed in group HCO + SO. Epidermal levels of GlcCer-C/D and SM-2/3 did not differ among groups. Conclusion: Dietary BO was more prominent for reversing epidermal hyperproliferation by enhancing Cer metabolism with increased levels of Cer1/2, GlcCer-A/B, and SM1 species, and of GCase proteins.

키워드

참고문헌

  1. Elias PM. Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 1983; 80(1 Suppl): 44s-49s.
  2. Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991; 24: 1-26.
  3. Harding CR. The stratum corneum: structure and function in health and disease. Dermatol Ther 2004; 17 Suppl 1: 6-15. https://doi.org/10.1111/j.1396-0296.2004.04S1001.x
  4. Hamanaka S, Hara M, Nishio H, Otsuka F, Suzuki A, Uchida Y. Human epidermal glucosylceramides are major precursors of stratum corneum ceramides. J Invest Dermatol 2002; 119(2): 416-423. https://doi.org/10.1046/j.1523-1747.2002.01836.x
  5. Uchida Y, Hara M, Nishio H, Sidransky E, Inoue S, Otsuka F, Suzuki A, Elias PM, Holleran WM, Hamanaka S. Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J Lipid Res 2000; 41(12): 2071-2082.
  6. Gray GM, Yardley HJ. Lipid compositions of cells isolated from pig, human, and rat epidermis. J Lipid Res 1975; 16(6): 434-440.
  7. Burr GO, Burr MM. Nutrition classics from The Journal of Biological Chemistry 82:345-67, 1929. A new deficiency disease produced by the rigid exclusion of fat from the diet. Nutr Rev 1973;31(8): 248-249.
  8. Wertz PW, Cho ES, Downing DT. Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat. Biochim Biophys Acta 1983; 753(3): 350-355. https://doi.org/10.1016/0005-2760(83)90058-9
  9. Prottey C. Essential fatty acids and the skin. Br J Dermatol 1976; 94(5): 579-585. https://doi.org/10.1111/j.1365-2133.1976.tb05151.x
  10. Ziboh VA, Chapkin RS. Biologic significance of polyunsaturated fatty acids in the skin. Arch Dermatol 1987; 123(12): 1686a-1690. https://doi.org/10.1001/archderm.1987.01660360127024
  11. Barre DE. Potential of evening primrose, borage, black currant, and fungal oils in human health. Ann Nutr Metab 2001; 45(2): 47-57. https://doi.org/10.1159/000046706
  12. Furse RK, Rossetti RG, Zurier RB. Gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory properties, blocks amplification of IL-1 beta production by human monocytes. J Immunol 2001; 167(1): 490-496. https://doi.org/10.4049/jimmunol.167.1.490
  13. Chung S, Kong S, Seong K, Cho Y. Gamma-linolenic acid in borage oil reverses epidermal hyperproliferation in guinea pigs. J Nutr 2002; 132(10): 3090-3097. https://doi.org/10.1093/jn/131.10.3090
  14. Cho Y, Ziboh VA. Nutritional modulation of guinea pig skin hyperproliferation by essential fatty acid deficiency is associated with selective down regulation of protein kinase C-beta. J Nutr 1995; 125(11): 2741-2750.
  15. Mohrhauer H, Holman RT. The Effect of Dose Level of Essential Fatty Acids Upon Fatty Acid Composition of the Rat Liver. J Lipid Res 1963; 4: 151-159.
  16. Kim Y, Song EH, Shin K, Lee Y, Cho Y. Dietary effect of silk protein on epidermal levels of free sphingoid bases and phosphate metabolites in NC/Nga mice. Korean J Nutr 2012; 45(2): 113-120. https://doi.org/10.4163/kjn.2012.45.2.113
  17. Wang LJ, Chen SJ, Chen Z, Cai JT, Si JM. Morphological and pathologic changes of experimental chronic atrophic gastritis (CAG) and the regulating mechanism of protein expression in rats. J Zhejiang Univ Sci B 2006; 7(8): 634-640. https://doi.org/10.1631/jzus.2006.B0634
  18. Takagi Y, Nakagawa H, Yaginuma T, Takema Y, Imokawa G. An accumulation of glucosylceramide in the stratum corneum due to attenuated activity of beta-glucocerebrosidase is associated with the early phase of UVB-induced alteration in cutaneous barrier function. Arch Dermatol Res 2005; 297(1): 18-25. https://doi.org/10.1007/s00403-005-0567-7
  19. Uchida Y, Behne M, Quiec D, Elias PM, Holleran WM. Vitamin C stimulates sphingolipid production and markers of barrier formation in submerged human keratinocyte cultures. J Invest Dermatol 2001; 117(5): 1307-1313. https://doi.org/10.1046/j.0022-202x.2001.01555.x
  20. Mizutani Y, Mitsutake S, Tsuji K, Kihara A, Igarashi Y. Ceramide biosynthesis in keratinocyte and its role in skin function. Biochimie 2009; 91(6): 784-790. https://doi.org/10.1016/j.biochi.2009.04.001
  21. Holleran WM, Takagi Y, Uchida Y. Epidermal sphingolipids: metabolism, function, and roles in skin disorders. FEBS Lett 2006; 580(23): 5456-5466. https://doi.org/10.1016/j.febslet.2006.08.039
  22. Bartke N, Hannun YA. Bioactive sphingolipids: metabolism and function. J Lipid Res 2009; 50 Suppl: S91-S96. https://doi.org/10.1194/jlr.R800080-JLR200
  23. Ohnishi Y, Okino N, Ito M, Imayama S. Ceramidase activity in bacterial skin flora as a possible cause of ceramide deficiency in atopic dermatitis. Clin Diagn Lab Immunol 1999; 6(1): 101-104.
  24. McCullough JL, Schreiber SH, Ziboh VA. Cell proliferation kinetics of epidermis in the essential fatty acid deficient rat. J Invest Dermatol 1978; 70(6): 318-320. https://doi.org/10.1111/1523-1747.ep12543484
  25. Tang W, Ziboh VA. Reversal of epidermal hyperproliferation in essential fatty acid deficient guinea pigs is accompanied by rapid generation of inositol triphosphate. Arch Dermatol Res 1988; 280(5): 286-292. https://doi.org/10.1007/BF00440602
  26. Kim J, Kim H, Jeong H, Kim SH, Park SK, Cho Y. Comparative effect of gromwell (Lithospermum erythrorhizon) extract and borage oil on reversing epidermal hyperproliferation in guinea pigs. Biosci Biotechnol Biochem 2006; 70(9): 2086-2095. https://doi.org/10.1271/bbb.60038
  27. Lampe MA, Williams ML, Elias PM. Human epidermal lipids: characterization and modulations during differentiation. J Lipid Res 1983; 24(2): 131-140.
  28. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, Lehmann JM. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A 1997; 94: 4318-4323. https://doi.org/10.1073/pnas.94.9.4318
  29. McCusker MM, Grant-Kels JM. Healing fats of the skin: the structural and immunologic roles of the ${\omega}$-6 and ${\omega}$-3 fatty acids. Clin Dermatol 2010; 28(4): 440-451. https://doi.org/10.1016/j.clindermatol.2010.03.020
  30. HogenEsch H, Boggess D, Sundberg JP. Changes in keratin and filaggrin expression in the skin of chronic proliferative dermatitis (cpdm) mutant mice. Pathobiology 1999; 67(1): 45-50. https://doi.org/10.1159/000028050

피인용 문헌

  1. Borage Oil Enhances Lamellar Body Content and Alters Fatty Acid Composition of Epidermal Ceramides in Essential Fatty ACID‐DEFICIENT Guinea Pigs vol.56, pp.3, 2015, https://doi.org/10.1002/lipd.12295