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LDHA 作为 T 细胞命运的调节剂及其在疾病中的机制。

LDHA as a regulator of T cell fate and its mechanisms in disease.

机构信息

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.

出版信息

Biomed Pharmacother. 2023 Feb;158:114164. doi: 10.1016/j.biopha.2022.114164. Epub 2023 Jan 4.

Abstract

T cells are the main force of anti-infection and antitumor and are also involved in autoimmune diseases. During the development of these diseases, T cells need to rapidly produce large amounts of energy to satisfy their activation, proliferation, and differentiation. In this review, we introduced lactate dehydrogenase A(LDHA), predominantly involved in glycolysis, which provides energy for T cells and plays a dual role in disease by mediating lactate production, non-classical enzyme activity, and oxidative stress. Mechanistically, the signaling molecule can interact with the LDHA promoter or regulate LDHA activity through post-translational modifications. These latest findings suggest that modulation of LDHA may have considerable therapeutic effects in diseases where T-cell activation is an important pathogenesis.

摘要

T 细胞是抗感染和抗肿瘤的主力军,也参与自身免疫性疾病的发生。在这些疾病的发展过程中,T 细胞需要迅速产生大量能量来满足其激活、增殖和分化的需要。在这篇综述中,我们介绍了糖酵解中起主要作用的乳酸脱氢酶 A(LDHA),它为 T 细胞提供能量,并通过介导乳酸生成、非经典酶活性和氧化应激在疾病中发挥双重作用。在机制上,信号分子可以与 LDHA 启动子相互作用或通过翻译后修饰来调节 LDHA 活性。这些最新发现表明,调节 LDHA 可能在 T 细胞激活是重要发病机制的疾病中具有相当大的治疗效果。

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