Journal of the Society of Cosmetic Scientists of Korea (대한화장품학회지)

Society of Cosmetic Scientists of Korea (대한화장품학회)
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A Study on the Inhibition of Skin Pigmentation by Lobaric Acid as Protease Activated Receptor-2 Antagonist

Protease Activated Receptor-2의 길항제로서 Lobaric Acid의 피부 색소침착 억제 효능 연구

  • Goo, Jung Hyun (Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University) ;
  • Lee, Ji Eun (Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University) ;
  • Myung, Cheol Hwan (Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University) ;
  • Park, Jong Il (Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University) ;
  • Hwang, Jae Sung (Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University)
  • Received : 2015.06.17
  • Accepted : 2015.07.28
  • Published : 2015.09.30
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Abstract

Melanosome, the pigment granule in melanocyte, determines the color of skin when it moves into the keratinocyte. Inhibition of melanosome transfer from melanocyte to keratinocyte results in skin depigmentation. Protease activated receptor-2 (PAR-2) is involved in signal transduction systems via cell membrane and increases the melasome transfer when it is activated by cleavage of their extracellular amino acid sequence by trypsin or by a peptide such as SLIGKV. Here, we showed that lobaric acid inhibited PAR-2 activation and affected the mobilization of $Ca2^+$. The uptake of fluorescent microspheres and isolated melanosomes from melan-a melanocytes to keratinocytes induced by SLIGKV were inhibited by lobaric acid. Also, confocal microscopy studies illustrated a decreased melanosome transfer to keratinocytes in melanocyte-keratinocyte co-culture system by lobaric acid. In addition, lobaric acid induced visible skin lightening effect in human skin tissue culture model, melanoderm$^{(R)}$. Our data suggest that lobaric acid could be an effective skin lightening agent that works via regulation of phagocytic activity of keratinocytes.

멜라노사이트에서 생성된 멜라노좀은 수상돌기를 따라 케라티노사이트로 이동한다. 세포막을 통한 정보 전달계에 관여하는 protease activated receptor-2 (PAR-2)는 SLIGKV와 같은 펩타이드에 의해 활성화되어 멜라노좀 전달을 증가하는 역할을 한다고 보고되어 있다. 본 연구에서는 새로운 PAR-2의 저해제를 찾고 본 저해제가 멜라노좀의 이동과 색소침착을 저해함을 확인하고자 하였다. PAR-2가 활성화되면 G 단백질이 방출되고, 이때 증가하는 세포 내 칼슘 이온 농도가 lobaric acid에 의하여 감소하는 것을 확인하여 lobaric acid가 PAR-2의 길항제로 작용할 수 있음을 발견하였다. 각질형성세포에서 SLIGKV에 의해 증가된 형광 비드 uptake가 lobaric acid에 의해 억제 되는 것을 확인하였고 또한, 분리된 멜라노좀을 이용한 시험에서도 동일한 경향을 나타내었다. 멜라노사이트와 케라티노사이트를 공동 배양하여 멜라노좀의 이동을 공초점 현미경으로 관찰한 결과, lobaric acid에 의해 멜라노좀의 전달이 억제되었다. 인공피부조직에 lobaric acid를 처리하였을 때 색소 침착이 억제됨을 확인하였고, 또한 Fontana-Masson 염색을 통해 멜라닌의 양이 감소함을 확인하였다. 이상의 결과를 통해 lobaric acid가 PAR-2 길항제로 작용함으로써 케라티노사이트로 멜라노좀 전달을 억제하고 이를 통해 피부 색소 침착을 저해함을 확인할 수 있었다.

Keywords

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