Balcos Marie Carmel, Kim Su Yeon, Jeong Hyo-soon, Yun Hye-young, Baek Kwang Jin, Kwon Nyoun Soo, Park Kyoung-chan, Kim Dong-seok
Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
Department of Dermatology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Kyoungki-do 463-707, Korea.
Acta Pharmacol Sin. 2014 Apr;35(4):489-95. doi: 10.1038/aps.2013.174. Epub 2014 Feb 24.
To investigate the effects of docosahexaenoic acid (DHA) on melanin synthesis and related regulatory mechanisms.
B16F10 mouse melanoma cells were exposed to DHA for 3 d, and melanin content and tyrosinase activity were measured. Western blot analysis was used to analyze the protein levels in DHA-mediated signal transduction pathways.
DHA (1-25 μmol/L) did not affect the viability of B16F10 cells, but decreased α-MSH-induced melanin synthesis in a concentration-dependent manner. DHA concentration-dependently reduced tyrosinase activity in the cells, but did not affect mushroom tyrosinase activity in a cell-free system. Furthermore, DHA treatment significantly reduced tyrosinase level without affecting microphthalmia-associated transcription factor (MITF) in the cells. DHA did not activate ERK and Akt in the cells. Pretreatment with the proteasome inhibitor MG132 (80 nmol/L) abolished DHA-induced tyrosinase reduction.
DHA inhibits melanogenesis in B16F10 cells in vitro through increasing tyrosinase degradation. The results suggest that DHA may be a potential agent for treatment of hyperpigmentary disorders of skin.
研究二十二碳六烯酸(DHA)对黑色素合成及相关调控机制的影响。
将B16F10小鼠黑色素瘤细胞暴露于DHA中3天,检测黑色素含量和酪氨酸酶活性。采用蛋白质免疫印迹分析(Western blot分析)来分析DHA介导的信号转导通路中的蛋白质水平。
DHA(1 - 25 μmol/L)不影响B16F10细胞的活力,但以浓度依赖的方式降低α - 促黑素(α - MSH)诱导的黑色素合成。DHA浓度依赖性地降低细胞中的酪氨酸酶活性,但不影响无细胞体系中蘑菇酪氨酸酶的活性。此外,DHA处理显著降低细胞中酪氨酸酶水平,但不影响小眼相关转录因子(MITF)。DHA未激活细胞中的细胞外信号调节激酶(ERK)和蛋白激酶B(Akt)。用蛋白酶体抑制剂MG132(80 nmol/L)预处理可消除DHA诱导的酪氨酸酶减少。
DHA通过增加酪氨酸酶降解在体外抑制B16F10细胞中的黑色素生成。结果表明,DHA可能是治疗皮肤色素沉着过度性疾病的潜在药物。