胡椒碱通过ERK激活和蛋白酶体降解MITF调节黑色素生成

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI:10.4062/biomolther.2024.065
Jun Hyeong Lee, Jieun Lee, Sukanya Dej-Adisai, Jae Sung Hwang
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引用次数: 0

摘要

黑色素是由黑色素细胞合成的一种生物色素分子。它的作用是保护皮肤免受紫外线辐射。然而,异常的黑色素生成,无论是过多还是缺乏,都会导致白癜风、雀斑、黑素细胞痣甚至黑色素瘤等疾病。黑色素的生物合成途径被称为黑色素生成,受多种转录因子和酶促过程的调节。胡椒碱(PPN)是一种从胡椒中提取的生物碱化合物。研究了其潜在的抗真菌和抗炎作用。我们的假设集中在PPN治疗对黑色素生物合成的抑制。随后,观察到PPN治疗导致黑色素生成的剂量依赖性减少,并伴有酪氨酸酶活性的降低。此外,PPN被发现下调黑素形成相关关键基因的蛋白水平。此外,PPN还能提高ERK的磷酸化水平。为了评估ERK信号在ppn诱导的黑色素形成调控中的作用,我们使用了ERK抑制剂PD98059。PD98059作用于melana细胞后,可恢复胡椒碱诱导的MITF表达水平和黑色素含量的降低。此外,ERK的磷酸化增加了MITF Ser73位点的磷酸化。这种磷酸化的MITF导致泛素化,最终,MITF的蛋白水平通过蛋白酶体降解而降低。同样,当用蛋白酶体抑制剂MG132处理melana细胞时,胡椒碱诱导的MITF表达水平降低和黑色素含量恢复。因此,PPN可以作为一个潜在的候选应用作为皮肤增白剂或在配方减轻色素沉着。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Piperine Regulates Melanogenesis through ERK Activation and Proteasomal Degradation of MITF.

Melanin is a bio-pigment molecule synthesized by melanocytes. Its role is to shield the skin from ultraviolet radiation. Nonetheless, aberrant melanin production, whether excessive or deficient, can lead to conditions such as vitiligo, freckles, melanocytic nevi, and even melanoma. The biosynthetic pathway of melanin is known as melanogenesis, which is regulated by various transcription factors and enzymatic processes. Piperine (PPN), an alkaloid compound extracted from Piper retrofractum Vahl., was investigated for its potential anti-fungal and anti-inflammatory effects. Our hypothesis centered on the inhibition of melanin biosynthesis in response to PPN treatment. Subsequently, it was observed that PPN treatment resulted in a dose-dependent reduction in melanin production, accompanied by a decrease in tyrosinase activity. Furthermore, PPN was found to downregulate the protein levels of key melanogenesis-related genes. Additionally, PPN was observed to elevate the phosphorylation levels of ERK. To assess the role of ERK signaling in PPN-induced melanogenesis regulation, PD98059, an ERK inhibitor, was used. When Melan-A cells were treated with PD98059, the reduced expression level of MITF and melanin content induced by piperine were restored. Additionally, phosphorylation of ERK increased the phosphorylation of MITF at Ser73. This phosphorylated MITF leads to ubiquitination, and ultimately, the protein level of MITF decreases through proteasomal degradation. Likewise, when Melan-A cells were treated with MG132, a proteasomal inhibitor, the reduced expression level of MITF and melanin content induced by piperine were restored. Consequently, PPN can be a potential candidate for application as a skin whitening agent or in formulations to mitigate hyperpigmentation.

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来源期刊
CiteScore
6.60
自引率
8.10%
发文量
72
审稿时长
6-12 weeks
期刊介绍: Biomolecules & Therapeutics (Biomolecules & Therapeutics) (Print ISSN 1976-9148, Online ISSN 2005-4483) is an international, peer-reviewed, open access journal that covers pharmacological and toxicological fields related to bioactive molecules and therapeutics. It was launched in 1993 as "The Journal of Applied Pharmacology (ISSN 1225-6110)", and renamed "Biomolecules & Therapeutics" (Biomol Ther: abbreviated form) in 2008 (Volume 16, No. 1). It is published bimonthly in January, March, May, July, September and November. All manuscripts should be creative, informative, and contribute to the development of new drugs. Articles in the following categories are published: review articles and research articles.
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