Jin Sun Hee, Lee Young Yi, Kang Hee Young
Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea.
Arch Dermatol Res. 2008 Sep;300(8):451-4. doi: 10.1007/s00403-008-0864-z. Epub 2008 May 14.
Cholesterol has been suggested to regulate cell differentiation. In this study, we have examined the effects of cholesterol modulation on pigmentation of skin using a treatment with methyl-beta-cyclodextrin (MbetaCD), a specific cholesterol-binding agent. Treatment with MbetaCD reduced pigmentation in human melanocyte and cultured skin. This decrease in pigmentation was related to the inhibition of the expression of tyrosinase and microphthalmia-associated transcription factor of melanocytes. Stimulation of melanocytes with MbetaCD led to the time-dependent phosphorylation of extracellular signal-regulated kinase (ERK). Furthermore, ERK functionally regulated the MbetaCD-induced melanin formation in melanocytes; a ERK inhibitor, PD98059, almost completely attenuated the MbetaCD-mediated inhibition of melanin synthesis and down-regulation of MITF and tyrosinase expression. These results suggest that cholesterol reduction by MbetaCD inhibit melanin synthesis via ERK activation and subsequent MITF downregulation.
胆固醇被认为可调节细胞分化。在本研究中，我们使用甲基-β-环糊精（MβCD，一种特异性胆固醇结合剂）处理，研究了胆固醇调节对皮肤色素沉着的影响。用MβCD处理可减少人黑素细胞和培养皮肤中的色素沉着。这种色素沉着的减少与黑素细胞中酪氨酸酶和小眼畸形相关转录因子表达的抑制有关。用MβCD刺激黑素细胞导致细胞外信号调节激酶（ERK）的时间依赖性磷酸化。此外，ERK在功能上调节MβCD诱导的黑素细胞中黑色素的形成；ERK抑制剂PD98059几乎完全减弱了MβCD介导的黑色素合成抑制以及MITF和酪氨酸酶表达的下调。这些结果表明，MβCD降低胆固醇通过ERK激活和随后的MITF下调来抑制黑色素合成。
