Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
권호 표지
DOI QR코드

DOI QR Code

The inhibitory effect of egg white lysosome extract (LOE) on melanogenesis through ERK and MITF regulation

  • Park, Jung Eun (School of Cosmetic Science and Beauty Biotechnology, Semyung University) ;
  • Hwang, Hyung Seo (School of Cosmetic Science and Beauty Biotechnology, Semyung University)
  • Received : 2022.04.07
  • Accepted : 2022.05.17
  • Published : 2022.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Lysosome organelle extract (LOE) was derived from egg whites. The lysosome is an intracellular organelle that contains several hydrolysis enzymes. Previous studies have reported that LOE performs important functions, such as melanin de-colorization and anti-melanin production in B16F10 melanoma cells. However, its principal molecular and cellular mechanisms have not been elucidated till date. In non-cytotoxic conditions, LOE significantly inhibited α-MSH induced melanin synthesis of murine B16F10 cells. The anti-melanogenic activity of LOE was mediated by suppressing the mRNA expression of tyrosinase enzyme, tyrosinase related protein-1/2 (TRP-1/2), and microphthalmia-associated transcription factor (MITF) genes. By performing western blot analysis, we found that LOE significantly attenuated melanogenesis. In this case, LOE helped in increasing extracellular receptor kinase (ERK) phosphorylation in α-MSH induced B16F10 cells. Furthermore, MITF is found to be a key regulatory transcription factor in melanin synthesis; it was down-regulated by LOE through ERK phosphorylation. In this experiment, PD98059 (MEK inhibitor) was used to check whether LOE directly regulated the activity of ERK. Although LOE exerted inhibitory effect on melanin synthesis, we could not observe this effect in PD98059-treated α-MSH induced B16F10. These results strongly indicate that LOE is related to ERK activation and MITF degradation in anti-skin pigmentation. Hence, LOE should be utilized as a whitening agent of skin in the near future.

Keywords

Acknowledgement

This research was financially supported by grants received from Ministry of Trade, Industry and Energy (MOTIE) and Korea Institute for Advancement of Technology (KIAT) (P0006145).

References

  1. D'Mello SAN, Finlay GJ, Baguley BC, Askarian-Amiri ME (2016) Signaling pathways in melanogenesis. Int J Mol Sci 17: 1144. doi: 10.3390/ijms17071144
  2. Murase D, Hachiya A, Amano Y, Ohuchi A, Kitahara T, Takema Y (2009) The essential role of p53 in hyperpigmentation of the skin via regulation of paracrine melanogenic cytokine receptor signaling. J Biol Chem 284: 4343-4353. doi: 10.1074/jbc.M805570200
  3. Busca R, Ballotti R (2000) Cyclic AMP a Key Messenger in the Regulation of Skin Pigmentation. Pigment CELL RES 13: 60-69. doi: 10.1034/j.1600-0749.2000.130203.x
  4. Aroca P, Urabe K, Kobayashi T, Tsukamoto K, Hearing BJ (1993) Melanin biosynthesis patterns following hormonal stimulation. J Biol Chem 268: 25650-25655. doi: 10.1016/s0021-9258(19)74439-1
  5. Kobayashi T, Urabe K, Winder A, Jimenez-Cervantes C, Imokawa G, Brewington T, Hearing VJ (1994) Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. EMBO J 13:5818-5825. doi: 10.1002/j.1460-2075.1994.tb06925.x
  6. Azam MS, Choi J, Lee MS, Kim HR (2017) Hypopigmenting effects of brown algae-derived phytochemicals: A review on molecular mechanisms. Mar Drugs 15: 297. doi: 10.3390/md15100297
  7. Saha B, Singh SK, Sarkar C, Bera R, Ratha J, Tobin DJ, Bhadra R (2006) Activation of the Mitf promoter by lipid-stimulated activation of p38-stress signalling to CREB. Pigment Cell Res 19: 595-605. doi: 10.1111/j.1600-0749.2006.00348.x
  8. Wu M, Hemesath TJ, Takemoto CM, Horstmann MA, Wells AG, Price ER, Fisher DE (2000) c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Genes Dev 14: 301-312. doi: 10.1101/gad.14.3.301
  9. Saftig P, Klumperman J (2009) Lysosome biogenesis and lysosomal membrane proteins: Trafficking meets function. Nat Rev Mol Cell Biol 10: 623-635. doi:10.1038/nrm2745
  10. Ballabio A (2016) The awesome lysosome. EMBO Mol Med 8: 73-76. doi: 10.15252/emmm.201505966
  11. Kroemer G, Jaattela M (2005) Lysosomes and autophagy in cell death control. Nat Rev Cancer 5: 886-897. doi:10.1038/nrc1738
  12. Yoon J, Kim YH, Ahn JY, Lee HC, Oh SJ, Chung BW, Min J (2017) Evaluation of in vitro function by subcellular distribution of lysosomal and peroxisomal protein in Saccharomyces cerevisiae. J Nanosci Nanotechnol 17: 244-250. doi: 10.1166/jnn.2017.12448
  13. Yoon J, Kim YH, Ahn JY, Lee HC, Oh SJ, Chung BW, Min J (2015) Melanin reduction by peroxidase activity in lysosome-related organelle extracts from hen egg whites, HeLa cells, and Saccharomyces cerevisiae. Mol Cell Toxicol 11: 441-447. doi: 10.1007/s13273-015-0047-x
  14. Yoon J, Park JM, Kim KJ, Kim YH, Min J (2009) Antimicrobial activity of the cell organelles, lysosomes, isolated from egg white. J Microbiol Biotechnol 19: 1364-1368. doi: 10.4014/jmb.0905.05053
  15. Choi DH, Jeon G, Yoon J, Min J, Park SJ, Kim JS, Hwang HS (2019) Study on the Whitening Efficacy and Skin Barrier by Lysosome-related Organelle Extract (LOE) from Egg White. J Soc Cosmet Sci Korea 45:389-397. doi: 10.15230/SCSK.2019.45.4.389
  16. Jeon G, Kim C, Cho UM, Hwang ET, Hwang HS, Min J (2021) Melanin-Decolorizing Activity of Antioxidant Enzymes, Glutathione Peroxidase, Thiol Peroxidase, and Catalase. Mol Biotechnol 63: 150-155. doi: 10.1007/s12033-020-00292-6
  17. Tadokoro T, Yamaguchi, Y, Batzer J, Coelho SG, Zmudzka BZ, Miller SA, Wolber R, Beer JZ, Hearing VJ (2005) Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation. J Investig Dermatol 124: 1326-1332. doi: 10.1111/j.0022-202X.2005.23760.x
  18. d'Ischia M, Wakamatsu K, Cicoira F, Mauro ED, Garcia-Borron JC, Commo S, Galvan I, Ghanem G, Kenzo K, Meredith P, Pezzella A, Santato C, Sarna T, Simon JD, Zecca L, Zucca FA, Napolitano A, Ito S (2015) Melanins and melanogenesis: From pigment cells to human health and technological applications. Pigment Cell Melanoma Res 28:520-544. doi: 10.1111/pcmr.12393
  19. Brenner M, Hearing VJ (2008) The protective role of melanin against UV damage in human skin. Photochem Photobiol 84: 539-549. doi: 10.1111/j.1751-1097.2007.00226.x
  20. Burger P, Landreau A, Azoulay S, Michel T, Fernandez X (2016) Skin whitening cosmetics: Feedback and challenges in the development of natural skin lighteners. Cosmetics 3: 36. doi: 10.3390/cosmetics3040036
  21. Couteau C, Coiffard L (2016) Overview of skin whitening agents: Drugs and cosmetic products. Cosmetics 3: 27. doi: 10.3390/cosmetics3030027
  22. Naidoo L, Khoza N, Dlova NC (2016) A fairer face, a fairer tomorrow? A review of skin lighteners. Cosmetics 3: 33. doi: 10.3390/cosmetics3030033
  23. Tsukamoto K, Jackson IJ, Urabe K, Montague PM, Hearing VJ (1992) A second tyrosinase-related protein, TRP2, is a melanogenic enzyme termed DOPAchrome tautomerase. EMBO J 11: 519-526. doi: 10.1002/j.1460-2075.1992.tb05082.x
  24. Su TR, Lin JJ, Tsai CC, Huang TK, Yang ZY, Wu MO, Zheng YQ, Su CC, Wu YJ (2013) Inhibition of melanogenesis by gallic acid: Possible involvement of the PI3K/Akt, MEK/ERK and Wnt/β-catenin signaling pathways in B16F10 cells. Int J Mol Sci 14: 20443-20458. doi: 10.3390/ijms141020443
  25. Khaled M, Larribere L, Bille K, Aberdam E, Ortonne JP, Ballotti R, Bertolotto C (2002) Glycogen synthase kinase 3β is activated by cAMP and plays an active role in the regulation of melanogenesis. J Biol Chem 277: 33690-33697. doi: 10.1074/jbc.M202939200
  26. Kim JH, Kim DH, Cho KM, Kim KH, Kang NJ (2018) Effect of 3,6-anhydro-l-galactose on α-melanocyte stimulating hormone-induced melanogenesis in human melanocytes and a skin-equivalent model. J Cell Biochem 119: 7643-7656. doi: 10.1002/jcb.27112
  27. Jin KS, Oh YN, Hyun SK, Kwon HJ, Kim BW (2014) Betulinic acid isolated from Vitis amurensis root inhibits 3-isobutyl-1-methylxanthine induced melanogenesis via the regulation of MEK/ERK and PI3K/Akt pathways in B16F10 cells. Food Chem Toxicol 68: 38-43. doi: 10.1016/j.fct.2014.03.001
  28. Lei L, Su J, Chen J, Chen W, Chen X, Peng C (2019) The role of lysophosphatidic acid in the physiology and pathology of the skin. Life Sci 220: 194-200. doi: 10.1016/j.lfs.2018.12.040
  29. Nakane S, Tokumura A, Waku K, Sugiura T (2001) Hen egg yolk and white contain high amounts of lysophosphatidic acids, growth factor-like lipids: Distinct molecular species compositions. Lipids 36: 413-419. doi: 10.1007/s11745-001-0737-1
  30. Kim DS, Park SH, Kwon SB, Youn SW, Park KC (2004) Effects of lysophosphatidic acid on melanogenesis. Chem Phys Lipids 127: 199-206. doi: 10.1016/j.chemphyslip.2003.11.002
  31. Serre C, Busuttil V, Botto JM (2018) Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation. Int J Cosmet Sci 40: 328-347. doi: 10.1111/ics.12466