评估替尼列汀和雷他列汀对 B16F1 细胞中黑色素吞噬作用清除黑色素小体的影响

IF 3.4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cosmetics Pub Date : 2024-03-01 DOI:10.3390/cosmetics11020035
Seong Hyun Kim, J. Bae, N. Park, Joon Bum Kim, Yong Hwan Kim, So Hyun Kim, Gyeong-Seok Oh, Hee Won Wang, Jeong Ho Chang, Dong-Hyung Cho
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引用次数: 0

摘要

黑色素体是一种特殊的膜结合细胞器,是黑色素储存和运输以及黑色素在黑色素细胞中合成的核心。尽管以前的研究已将黑色素体的降解与自噬联系起来,但其确切的机制仍然难以捉摸。自噬是一个复杂的分解过程,涉及自噬体和溶酶体,在细胞成分降解中发挥着重要作用。在这项研究中,我们采用了一种基于细胞的筛选系统,旨在揭示关键的途径调节因子,从而探索自噬在黑色素体降解中的作用。我们通过对泛素化相关化学库的全面筛选,发现了特异性二肽基肽酶-4 抑制剂,如氢溴酸替尼列汀和磷酸雷他列汀,它们是诱导黑色素吞噬的新型药物。我们发现,用氢溴酸替格列汀或磷酸雷他列汀治疗,不仅能减少α-黑色素细胞刺激素(α-MSH)升高的黑色素含量,还能引发B16F1细胞内的自噬激活。此外,对unc-51-like激酶(ULK1)的靶向抑制能显著减轻氢溴酸替尼列汀和磷酸雷他列汀对α-MSH处理细胞的抗色素沉着作用和自噬诱导。总之,我们的数据为了解黑色素体降解提供了一个新的领域,确定了氢溴酸替格列汀和磷酸瑞格列汀是通过激活自噬诱导黑色素吞噬的有前途的诱导剂。这项研究有助于深入了解细胞降解机制,并为色素沉着的调控提供了潜在的治疗途径。
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Evaluation of Teneligliptin and Retagliptin on the Clearance of Melanosome by Melanophagy in B16F1 Cells
A specialized membrane-bound organelle, named the melanosome, is central to the storage and transport of melanin as well as melanin synthesis in melanocytes. Although previous studies have linked melanosomal degradation to autophagy, the precise mechanisms remain elusive. Autophagy, a complex catabolic process involving autophagosomes and lysosomes, plays a vital role in cellular constituent degradation. In this study, the role of autophagy in melanosomal degradation was explored, employing a cell-based screening system designed to unveil key pathway regulators. We identified specific dipeptidyl peptidase-4 inhibitors, such as teneligliptin hydrobromide and retagliptin phosphate, as novel agents inducing melanophagy through a comprehensive screening of a ubiquitination-related chemical library. We found that treatment with teneligliptin hydrobromide or retagliptin phosphate not only diminishes melanin content elevated by alpha-melanocyte-stimulating hormone (α-MSH) but also triggers autophagy activation within B16F1 cells. In addition, the targeted inhibition of unc-51-like kinase (ULK1) significantly attenuated both the anti-pigmentation effects and autophagy induced by teneligliptin hydrobromide and retagliptin phosphate in α-MSH-treated cells. Collectively, our data demonstrate a new frontier in understanding melanosomal degradation, identifying teneligliptin hydrobromide and retagliptin phosphate as promising inducers of melanophagy via autophagy activation. This study contributes essential insights into cellular degradation mechanisms and offers potential therapeutic avenues in the regulation of pigmentation.
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来源期刊
Cosmetics
Cosmetics Medicine-Surgery
CiteScore
5.20
自引率
12.10%
发文量
108
审稿时长
8 weeks
期刊最新文献
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