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谷胱甘肽过氧化物酶4(GPX4)在皮肤稳态与疾病中的双刃剑效应

Double-edged sword effect of GPX4 in skin homeostasis and diseases.

作者信息

Xu Hanzhang, Yang Li, Wu Yingli, Lei Hu

机构信息

Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Pathophysiology, Research Unit of Stress and Cancer, Chinese Academy of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Arch Dermatol Res. 2025 Feb 14;317(1):404. doi: 10.1007/s00403-025-03903-x.

Abstract

Glutathione peroxidase 4 (GPX4) is a crucial antioxidant enzyme that plays a vital role in protecting cells from oxidative damage and lipid peroxidation. In the context of skin diseases, GPX4 serves as a key regulator of oxidative stress and inflammation, both of which are significant features of various skin conditions. By preventing lipid peroxidation and maintaining membrane integrity, GPX4 acts as a safeguard against cell death pathways, particularly ferroptosis, in skin diseases. Dysregulation of GPX4 in conditions such as dermatitis, psoriasis, and skin cancer is linked to heightened oxidative stress, inflammation, and tissue damage. Understanding the role of GPX4 and its intricate interactions in skin disease pathogenesis can aid in more effectively targeting oxidative stress and inflammation, leading to promising therapeutic interventions. This review summarizes the role of GPX4 in maintaining skin homeostasis and its involvement in disease, proposing strategies to target GPX4, including its post-translational modifications. Investigate the precise mechanism through which GPX4 influences the onset of skin diseases, and utilize GPX4 agonists or inhibitors as potential treatments.

摘要

谷胱甘肽过氧化物酶4(GPX4)是一种关键的抗氧化酶,在保护细胞免受氧化损伤和脂质过氧化方面发挥着至关重要的作用。在皮肤疾病的背景下,GPX4是氧化应激和炎症的关键调节因子,而氧化应激和炎症是各种皮肤状况的重要特征。通过防止脂质过氧化并维持膜完整性,GPX4在皮肤疾病中作为细胞死亡途径(特别是铁死亡)的一种保护机制。在皮炎、银屑病和皮肤癌等病症中,GPX4的失调与氧化应激加剧、炎症和组织损伤有关。了解GPX4在皮肤疾病发病机制中的作用及其复杂的相互作用,有助于更有效地针对氧化应激和炎症,从而带来有前景的治疗干预措施。本综述总结了GPX4在维持皮肤稳态中的作用及其与疾病的关联,提出了针对GPX4的策略,包括其翻译后修饰。研究GPX4影响皮肤疾病发病的确切机制,并将GPX4激动剂或抑制剂用作潜在治疗方法。

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