胎盘提取物通过诱导酪氨酸酶和TRP-1的蛋白酶体依赖性降解来抑制黑色素生成。

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Mie Moriya
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引用次数: 0

摘要

在日本,胎盘提取物(PE)被用作皮肤增白剂,这种材料被用于化妆品和膳食补充剂中。然而,PE抗黑素活性的机制尚不清楚。本研究的目的是阐明PE对B16小鼠黑色素瘤细胞黑素生成的抑制作用机制。研究了马PE (EPE)对酪氨酸酶和黑色素生成蛋白的活性。采用分光光度法测定EPE对酪氨酸酶活性和黑色素含量的影响。该分析表明,EPE以剂量依赖的方式抑制黑色素瘤细胞的黑色素生成,而不影响细胞增殖。EPE对酪氨酸酶活性无直接抑制作用。Western blot分析表明,EPE暴露也导致黑色素瘤细胞中酪氨酸酶和酪氨酸酶相关蛋白1 (TRP-1)蛋白水平降低,但不影响编码这些蛋白的mrna水平。该分析进一步证明,EPE诱导酪氨酸酶和TRP-1的消耗是由EPE诱导蛋白酶体介导的蛋白水解降解引起的。值得注意的是,通过联合暴露于EPE和蛋白酶体抑制剂MG132, EPE诱导的酪氨酸酶和TRP-1的消耗被阻止。类似的实验表明,黑色素瘤细胞暴露于MG132后,EPE对黑色素形成的抑制作用被取消。免疫沉淀分析进一步显示EPE诱导酪氨酸酶和TRP-1泛素化。综上所述,这些结果表明,EPE通过增强这些靶点的泛素化,诱导酪氨酸酶和TRP-1的蛋白酶体降解,导致这些蛋白质的消耗和黑素生成的抑制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Placental Extract Inhibits Melanogenesis by Inducing the Proteasome-Dependent Degradation of Tyrosinase and TRP-1.

Placental extract (PE) is employed as a skin-whitening agent in Japan, where this material is used in cosmetics and dietary supplements. However, the mechanism of PE's anti-melanogenic activity remains poorly understood. The goal of the present study was to elucidate the mechanism of PE's inhibitory effect on melanogenesis in B16 murine melanoma cells. Specifically, the activity of equine PE (EPE) against tyrosinase and melanogenic proteins was evaluated. The effects of EPE on tyrosinase activity and melanin content were assessed spectrophotometrically. This analysis showed that EPE inhibits melanogenesis in melanoma cells in a dose-dependent manner without affecting cell proliferation. EPE did not directly inhibit the enzymatic activity of tyrosinase. Western blot analysis demonstrated that EPE exposure also led to decreases in the protein levels of tyrosinase and tyrosinase-related protein 1 (TRP-1) in melanoma cells, without affecting the levels of the mRNAs encoding these proteins. This analysis further demonstrated that the EPE-induced depletion of tyrosinase and TRP-1 resulted from the induction, by EPE, of proteasome-mediated proteolytic degradation. Notably, the EPE-induced depletion of tyrosinase and TRP-1 was prevented by joint exposure to EPE and the proteasome inhibitor MG132. Similar experiments showed that the exposure of melanoma cells to MG132 abrogates the inhibition of melanogenesis by EPE. Immunoprecipitation analysis further revealed that EPE induces the ubiquitination of tyrosinase and TRP-1. Taken together, these results suggested that EPE induces proteasomal degradation of tyrosinase and TRP-1 by enhancing the ubiquitination of these targets, leading to the depletion of these proteins and the inhibition of melanogenesis.

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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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