Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels
Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels
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DOI：
10.3390/ijms20225665
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Lim, Kyung-Min
中科院分区：
文献类型：
--
作者：
Kim, Minjeong;Lee, Chang-Seok;Lim, Kyung-Min
杜鹃花醇（RD）是一种美白化妆品成分，由于 RD 诱发白斑病（RIL）而被撤出市场。尽管人们已经做出了许多尝试来阐明 RIL 的底层机制，但 RIL 尚未被完全理解。事实上，受影响的受试者表现出不均匀的皮肤色素沉着，但其特征与白癜风（一种皮肤色素减退性疾病）不同，暗示着比简单的黑素细胞细胞毒性更复杂的事件。在这里，我们发现杜鹃花醇治疗减少了色素 3D 人类皮肤模型 Melanoderm (TM) 中黑色素细胞的数量，证实了 RD 的黑色素细胞毒性。值得注意的是，在 RD 处理的组织中存活的黑素细胞表现出形态改变，例如树突延长和细胞大小增加。与此一致的是，RD 的亚细胞毒性水平增加了 B16 黑色素瘤细胞中的细胞大小和拉长的树突。 B16 细胞的形态学变化在处理细胞的肌动蛋白和微管蛋白免疫细胞化学中得到进一步证实。更令人兴奋的是，RD 上调了存活的 B16 细胞中酪氨酸酶和 TRP1 的表达。对细胞骨架蛋白 mRNA 表达的评估表明，RD 改变了细胞骨架动态，有利于细胞大小扩张和黑素体成熟。总的来说，这些结果表明 RD 不仅会诱导黑素细胞的细胞毒性，而且甚至在亚细胞毒性水平下也会导致黑素细胞完整性的严重扰动。
Rhododenol (RD), a whitening cosmetic ingredient, was withdrawn from the market due to RD-induced leukoderma (RIL). While many attempts have been made to clarify the mechanism underlying RIL, RIL has not been fully understood yet. Indeed, affected subjects showed uneven skin pigmentation, but the features are different from vitiligo, a skin hypopigmentary disorder, alluding to events more complex than simple melanocyte cytotoxicity. Here, we discovered that rhododenol treatment reduced the number of melanocytes in a pigmented 3D human skin model, Melanoderm (TM), confirming the melanocyte toxicity of RD. Of note, melanocytes that survived in the RD treated tissues exhibited altered morphology, such as extended dendrites and increased cell sizes. Consistently with this, sub-cytotoxic level of RD increased cell size and elongated dendrites in B16 melanoma cells. Morphological changes of B16 cells were further confirmed in the immunocytochemistry of treated cells for actin and tubulin. Even more provoking, RD up-regulated the expression of tyrosinase and TRP1 in the survived B16 cells. Evaluation of mRNA expression of cytoskeletal proteins suggests that RD altered the cytoskeletal dynamic favoring cell size expansion and melanosome maturation. Collectively, these results suggest that RD not only induces cytotoxicity in melanocytes but also can lead to a profound perturbation of melanocyte integrity even at sub-cytotoxic levels.