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세신추출물이 α-MSH 자극에 의한 B16F10 세포의 멜라닌생성에 미치는 영향

Studies of Inhibitory Mechanism on Melanogenesis by Partially Purified Asiasari radix in α-MSH Stimulated B16F10 Melanoma Cells

  • 장지연 (부산대학교 한의학전문대학원 경락구조의학부) ;
  • 김하늬 (부산대학교 한의학전문대학원 경락구조의학부) ;
  • 김유리 (부산대학교 한의학전문대학원 경락구조의학부) ;
  • 김병우 (동의대학교 자연과학대학 생명응용과학과) ;
  • 최영현 (동의대학교 한의과대학 생화학교실) ;
  • 최병태 (부산대학교 한의학전문대학원 경락구조의학부)
  • Jang, Ji-Yeon (Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University) ;
  • Kim, Ha-Neui (Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University) ;
  • Kim, Yu-Ri (Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University) ;
  • Kim, Byung-Woo (Department of Life Science and Biotechnology, College of Natural Sciences, Dongeui University) ;
  • Choi, Yung-Hyun (Department of Biochemistry, College of Oriental Medicine, Dongeui University) ;
  • Choi, Byung-Tae (Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University)
  • 투고 : 2010.07.20
  • 심사 : 2010.11.03
  • 발행 : 2010.11.30

초록

$\alpha$-MSH는 세포내 cAMP를 증폭시켜 멜라닌세포의 증식과 색소 증가에 관여한다. 본 연구에서는 $\alpha$-MSH로 자극한 B16F10 세포에서 세신추출물의 hypopigmenting 효과를 조사하고 그 억제기전에 대하여 조사하였다. 세신추출물은 $\alpha$-MSH에 의해 유도된 tyrosinase 활성과 멜라닌생성을 효과적으로 억제시켰으며, 이는 tyrosinase 발현을 조절하는 전사인자인 MITF의 발현억제와 연관성이 있었다. 즉 세신추출물은 MEK/ERK와 PI3K/Akt의 활성화를 통하여 MITF를 조절함으로서 $\alpha$-MSH에 의해 유도되는 tyrosinase, TRP-1, Dct 등 멜라닌생성관련 단백질을 억제함으로서 멜라닌생성을 저해하는 것으로 사료된다.

Recently, it has been found that Asiasari radix showed a hypopigmenting effect on melanogenesis through activation of mitogen-activated protein kinase (MEK)/extracellular signal-activated kinase (ERK) in B16F10 melanoma cells. However, the hypopigmenting effect of A. radix on the $\alpha$-melanocyte stimulating hormone ($\alpha$-MSH)-stimulated melanogenesis has remained unknown. The purpose of this study was to investigate the inhibitory mechanism of the partially purified A. radix (PPAR)-induced hypopigmentating effects on $\alpha$-MSH-stimulated melanogenesis in B16F10 mouse melanoma cells. PPAR strongly inhibited tyrosinase activity and leads to decreased melanin synthesis in $\alpha$-MSH-stimulated B16F10 melanoma cells. PPAR also decreased the $\alpha$-MSH-induced over-expression of the melanogenic enzymes, tyrosinase, tyrosinase-related protein (TRP)-1, dopachrome tautomerase (Dct) and microphthalmia-associated transcription factor (MITF). We further showed that PPAR inhibits $\alpha$-MSH-induced melanogenesis via phosphorylation of MEK/ERK and PI3K/Akt, and that their activation was blocked by MEK inhibitors, PD98059 and PI3K inhibitors, LY294002 in $\alpha$-MSH-stimulated B16F10 melanoma cells. These results suggest that PPAR inhibits $\alpha$-MSH-induced melanogenesis by activation of MEK/ERK and PI3K/Akt through MITF degradation, which may lead to down-regulation of tyrosinase.

키워드

참고문헌

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