Choi Yeong-Gon, Bae Eun-Jin, Kim Dong-Seok, Park Seo-Hyoung, Kwon Sun-Bang, Na Jung-Im, Park Kyoung-Chan
Department of Dermatology, Seoul National University College of Medicine, Republic of Korea.
J Dermatol Sci. 2006 Sep;43(3):181-8. doi: 10.1016/j.jdermsci.2006.05.003. Epub 2006 Jun 15.
Melanogenesis is regulated by a series of enzymes under the control of microphthalmia-associated transcription factor (MITF).
The aim of this study was to examine melanosome-associated protein levels in Mel-Ab cells after hinokitiol treatment.
We measured melanin contents and analyzed melanosome-associated protein levels using Western blot and RT-PCR analysis.
Hinokitiol markedly inhibited melanin synthesis and also reduced the protein levels of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP-1), tyrosinase-related protein 2 (TYRP-2) and MITF in Mel-Ab cells. In addition, hinokitiol significantly increased the phosphorylations of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that TYR and MITF mRNA levels were significantly decreased but that levels of TYRP-1 and TYRP-2 mRNA were unaffected by hinokitiol treatment. These results suggest that hinokitiol-induced ERK phosphorylation reduces MITF and TYR transcription, and mediates the action of hinokitiol on melanogenesis. Interestingly, the mRNAs of TYRP-1 and TYRP-2 were unaffected, although the protein levels of TYRP-1 and TYRP-2 were down-regulated. Thus, the effects of hinokitiol on the transcription of TYR may differ from its effects on TYRP-1 and TYRP-2.
Therefore, we suggest that TYRP-1 and TYRP-2 may be regulated by post-translational degradation after hinokitiol treatment.
黑色素生成受小眼畸形相关转录因子(MITF)调控的一系列酶的调节。
本研究旨在检测扁柏酚处理后Mel-Ab细胞中黑素小体相关蛋白水平。
我们使用蛋白质免疫印迹法和逆转录-聚合酶链反应(RT-PCR)分析来测量黑色素含量并分析黑素小体相关蛋白水平。
扁柏酚显著抑制黑色素合成,还降低了Mel-Ab细胞中酪氨酸酶(TYR)、酪氨酸酶相关蛋白1(TYRP-1)、酪氨酸酶相关蛋白2(TYRP-2)和MITF的蛋白水平。此外,扁柏酚显著增加细胞外信号调节激酶1和2(ERK1/2)的磷酸化。此外,逆转录-聚合酶链反应(RT-PCR)分析显示,TYR和MITF的mRNA水平显著降低,但TYRP-1和TYRP-2的mRNA水平不受扁柏酚处理的影响。这些结果表明,扁柏酚诱导的ERK磷酸化降低了MITF和TYR的转录,并介导了扁柏酚对黑色素生成的作用。有趣的是,尽管TYRP-1和TYRP-2的蛋白水平下调,但其mRNA水平未受影响。因此,扁柏酚对TYR转录的影响可能与其对TYRP-1和TYRP-2的影响不同。
因此,我们认为扁柏酚处理后TYRP-1和TYRP-2可能通过翻译后降解进行调控。