School of Kinesiology, Shanghai University of Sport, Shanghai, China.
Exercise Biological Center, China Institute of Sport Science, Beijing, China.
Front Immunol. 2024 Jun 28;15:1391355. doi: 10.3389/fimmu.2024.1391355. eCollection 2024.
Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that exhibits Ca permeability. The TRPM2 channel is expressed in various tissues and cells and can be activated by multiple factors, including endogenous ligands, Ca, reactive oxygen species (ROS) and temperature. This article reviews the multiple roles of the TRPM2 channel in physiological and pathological processes, particularly on oxidative stress, inflammation and ischemia-reperfusion (I/R) injury. In oxidative stress, the excessive influx of Ca caused by the activation of the TRPM2 channel may exacerbate cellular damage. However, under specific conditions, activating the TRPM2 channel can have a protective effect on cells. In inflammation, the activation of the TRPM2 channel may not only promote inflammatory response but also inhibit inflammation by regulating ROS production and bactericidal ability of macrophages and neutrophils. In I/R, the activation of the TRPM2 channel may worsen I/R injury to various organs, including the brain, heart, kidney and liver. However, activating the TRPM2 channel may protect the myocardium from I/R injury by regulating calcium influx and phosphorylating proline-rich tyrosine kinase 2 (Pyk2). A thorough investigation of the bidirectional role and regulatory mechanism of the TRPM2 channel in these physiological and pathological processes will aid in identifying new targets and strategies for treatment of related diseases.
瞬时受体电位 melastatin 2（TRPM2）是一种非选择性阳离子通道，具有 Ca 通透性。TRPM2 通道在多种组织和细胞中表达，可被多种因素激活，包括内源性配体、Ca、活性氧（ROS）和温度。本文综述了 TRPM2 通道在生理和病理过程中的多种作用，特别是在氧化应激、炎症和缺血再灌注（I/R）损伤中。在氧化应激中，TRPM2 通道的激活导致 Ca 内流过多，可能加重细胞损伤。然而，在特定条件下，激活 TRPM2 通道对细胞具有保护作用。在炎症中，TRPM2 通道的激活不仅可以促进炎症反应，还可以通过调节巨噬细胞和中性粒细胞的 ROS 产生和杀菌能力来抑制炎症。在 I/R 中，TRPM2 通道的激活可能会使脑、心、肾和肝等各种器官的 I/R 损伤恶化。然而，通过调节 Ca 内流和磷酸化脯氨酸丰富的酪氨酸激酶 2（Pyk2），激活 TRPM2 通道可能会保护心肌免受 I/R 损伤。深入研究 TRPM2 通道在这些生理和病理过程中的双向作用和调节机制，将有助于确定治疗相关疾病的新靶点和策略。
