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氨基酸转运蛋白 SLC16A10 通过促进苯丙氨酸的转运来促进黑色素生成。

The amino acid transporter SLC16A10 promotes melanogenesis by facilitating the transportation of phenylalanine.

机构信息

Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

Center of Medical Laboratory Animal, Hunan Academy of Chinese Medicine, Changsha, Hunan, China.

出版信息

Exp Dermatol. 2024 Aug;33(8):e15165. doi: 10.1111/exd.15165.

Abstract

Phenylalanine is a crucial amino acid in the process of melanogenesis. However, the exact mechanism by which it is transported into melanocytes has not been disclosed. The aim of this study was to identify and examine the key transporters that are responsible for phenylalanine transportation and evaluate their significance in melanogenesis. The amino acid transporter SLC16A10 was found to be up-regulated in both melasma (GSE72140) and sun-exposed skin (GSE67098). The protein levels of SLC16A10 were proportional to the melanin content in melanocytic nevi, indicating that SLC16A10 was related to melanogenesis. After SLC16A10 overexpression, melanin increased significantly in MNT1 cells. Meanwhile, the expression of melanogenesis-related proteins such as TYR and TYRP1 increased, while their RNA levels did not change. Transcriptomics data indicated that SLC16A10 can enhance the function of ribosome. Furthermore, targeted metabolomics data and ELISA results demonstrated SLC16A10 mainly affected the transport of phenylalanine into the cells. Then, phenylalanine was added to the cell culture medium after SLC16A10 overexpression, melanin synthesis in cells furtherly increased, which verified that SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine. Finally, we found that SLC16A10 expression increased after UVB irradiation. Knockdown SLC16A10 reduced UVB-induced melanin production and phenylalanine uptake by cells. In summary, SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine, and upregulation SLC16A10 is likely responsible for the UVB-induced hyperpigmentation as well.

摘要

苯丙氨酸是黑色素生成过程中的一种关键氨基酸。然而,其进入黑色素细胞的具体运输机制尚未被揭示。本研究旨在鉴定和研究负责苯丙氨酸运输的关键转运体,并评估它们在黑色素生成中的重要性。氨基酸转运蛋白 SLC16A10 在黄褐斑(GSE72140)和暴露于阳光的皮肤(GSE67098)中均上调。SLC16A10 的蛋白水平与黑色素细胞痣中的黑色素含量成正比,表明 SLC16A10 与黑色素生成有关。SLC16A10 过表达后,MNT1 细胞中的黑色素明显增加。同时,黑色素生成相关蛋白如 TYR 和 TYRP1 的表达增加,而其 RNA 水平没有变化。转录组学数据表明 SLC16A10 可以增强核糖体的功能。此外,靶向代谢组学数据和 ELISA 结果表明 SLC16A10 主要影响苯丙氨酸进入细胞的运输。然后,在 SLC16A10 过表达后将苯丙氨酸添加到细胞培养基中,细胞中的黑色素合成进一步增加,这验证了 SLC16A10 通过促进苯丙氨酸的摄取来增强黑色素生成。最后,我们发现 SLC16A10 的表达在 UVB 照射后增加。SLC16A10 的敲低减少了细胞中由 UVB 诱导的黑色素生成和苯丙氨酸摄取。总之,SLC16A10 通过促进苯丙氨酸的摄取来增强黑色素生成,并且 SLC16A10 的上调可能是 UVB 诱导的色素沉着过度的原因之一。

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