The dual missions of FoxO3a in inflammatory diseases: Regulation of antioxidant enzymes and involvement in programmed cell death

IF 4.7 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-04-04 Epub Date: 2025-03-02 DOI:10.1016/j.intimp.2025.114369

Xiangli Ma , Yujie Lin , Ling Zhang , Zhenzhen Huang , Yurong Zhang , Xu Fu , Peiwu Li

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Abstract

The transcription factor FoxO3a plays a crucial role in the process of cells adapting to various stress conditions. Multiple post - translational modifications and epigenetic mechanisms work together to precisely regulate the activity of FoxO3a, influencing its subcellular localization, stability, interactions with other proteins, DNA - binding affinity, and transcriptional regulatory capacity. Under different chemical signal stimuli and subcellular environments, the activation of FoxO3a triggered by oxidative stress can initiate diverse transcriptional programs, which are essential for the body to resist oxidative damage. In the development and progression of inflammatory diseases, FoxO3a exerts an important function by regulating the expression levels of antioxidant enzymes and participating in key physiological processes such as programmed cell death. This article comprehensively reviews the structural characteristics, mechanism of action of FoxO3a, as well as its functions in regulating antioxidant enzymes and programmed cell death. The aim is to deeply explore the potential of FoxO3a as a potential therapeutic target for preventing and treating damages such as inflammatory diseases caused by cellular stress.

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FoxO3a在炎性疾病中的双重使命：调控抗氧化酶和参与程序性细胞死亡

转录因子FoxO3a在细胞适应各种应激条件的过程中起着至关重要的作用。多种翻译后修饰和表观遗传机制共同作用，精确调节FoxO3a的活性，影响其亚细胞定位、稳定性、与其他蛋白质的相互作用、DNA结合亲和力和转录调控能力。在不同的化学信号刺激和亚细胞环境下，氧化应激触发的FoxO3a激活可启动多种转录程序，这些转录程序是机体抵抗氧化损伤所必需的。在炎症性疾病的发生发展过程中，FoxO3a通过调节抗氧化酶的表达水平，参与细胞程序性死亡等关键生理过程发挥重要作用。本文就FoxO3a的结构特点、作用机制及其在调控抗氧化酶和程序性细胞死亡中的作用作一综述。目的是深入探索FoxO3a作为预防和治疗细胞应激引起的炎症性疾病等损伤的潜在治疗靶点的潜力。

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

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.