Unfolded protein response modulates Tyrosinase levels and melanin production during melanogenesis.

IF 4.6

Journal of dermatological science Pub Date : 2025-01-08 DOI:10.1016/j.jdermsci.2025.01.001

Akari Yamazaki, Issei Omura, Yasunao Kamikawa, Michihiro Hide, Akio Tanaka, Masayuki Kaneko, Kazunori Imaizumi, Atsushi Saito

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引用次数: 0

Abstract

Background: Melanocytes protect the body from ultraviolet radiation by synthesizing melanin. Tyrosinase, a key enzyme in melanin production, accumulates in the endoplasmic reticulum (ER) during melanin synthesis, potentially causing ER stress. However, regulating ER function for melanin synthesis has been less studied than controlling Tyrosinase activity.

Objective: This study investigates the regulatory mechanisms of melanin production, focusing on ER stress and the ER stress-induced response.

Methods: B16 mouse melanoma cells induced to undergo melanogenesis were treated with unfolded protein response (UPR) inhibitors or chemical chaperones, and their effects on melanogenesis were analyzed.

Results: During melanogenesis in B16 cells stimulated by alpha-melanocyte-stimulating hormone (α-MSH), ER stress and UPR activation occurred, accompanied by increased Tyrosinase protein. Reducing IRE1 and ATF6 branch activity lowered melanin levels, while chemical chaperone treatment restored melanin production and increased Tyrosinase levels.

Conclusion: UPR activation, linked to elevated Tyrosinase levels, influences melanin production during melanogenesis. Modulating UPR can regulate melanin synthesis and provides a potential new approach for treating pigmentation disorders.

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未折叠蛋白反应调节酪氨酸酶水平和黑色素生成过程中的黑色素。

背景：黑色素细胞通过合成黑色素保护人体免受紫外线辐射。酪氨酸酶是黑色素生成的关键酶，在黑色素合成过程中在内质网（ER）中积累，可能导致内质网应激。然而，与控制酪氨酸酶活性相比，调节内质网功能对黑色素合成的影响研究较少。目的：研究内质网应激和内质网应激诱导的黑色素生成调控机制。方法：采用未折叠蛋白反应（UPR）抑制剂或化学伴侣对诱导黑色素生成的B16小鼠黑色素瘤细胞进行处理，分析其对黑色素生成的影响。结果：α-MSH刺激B16细胞黑素形成过程中，内质网应激和UPR激活，酪氨酸酶蛋白升高。降低IRE1和ATF6分支活性降低黑色素水平，而化学伴侣处理恢复黑色素生成并增加酪氨酸酶水平。结论：UPR激活与酪氨酸酶水平升高有关，影响黑色素形成过程中黑色素的产生。调节UPR可以调节黑色素的合成，为治疗色素沉着疾病提供了潜在的新途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of dermatological science Dermatology

CiteScore

7.60

自引率

0.00%

发文量