Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, Poland.
Department of General Orthopaedics, Musculoskeletal Oncology and Trauma Surgery, University of Medical Sciences, 61-701 Poznan, Poland.
Int J Mol Sci. 2021 Jul 16;22(14):7635. doi: 10.3390/ijms22147635.
The transient receptor potential (TRP) melastatin-like subfamily member 2 (TRPM2) is a non-selective calcium-permeable cation channel. It is expressed by many mammalian tissues, including bone marrow, spleen, lungs, heart, liver, neutrophils, and endothelial cells. The best-known mechanism of TRPM2 activation is related to the binding of ADP-ribose to the nudix-box sequence motif (NUDT9-H) in the C-terminal domain of the channel. In cells, the production of ADP-ribose is a result of increased oxidative stress. In the context of endothelial function, TRPM2-dependent calcium influx seems to be particularly interesting as it participates in the regulation of barrier function, cell death, cell migration, and angiogenesis. Any impairments of these functions may result in endothelial dysfunction observed in such conditions as atherosclerosis or hypertension. Thus, TRPM2 seems to be an attractive therapeutic target for the conditions connected with the increased production of reactive oxygen species. However, before the application of TRPM2 inhibitors will be possible, some issues need to be resolved. The main issues are the lack of specificity, poor membrane permeabilization, and low stability in in vivo conditions. The article aims to summarize the latest findings on a role of TRPM2 in endothelial cells. We also show some future perspectives for the application of TRPM2 inhibitors in cardiovascular system diseases.
瞬时受体电位（TRP）melastatin 样亚家族成员 2（TRPM2）是一种非选择性钙通透阳离子通道。它在许多哺乳动物组织中表达，包括骨髓、脾脏、肺、心脏、肝脏、中性粒细胞和内皮细胞。TRPM2 激活的最著名机制与 ADP-核糖与通道 C 末端结构域中的 nudix 盒序列基序（NUDT9-H）结合有关。在细胞中，ADP-核糖的产生是氧化应激增加的结果。在内皮功能方面，TRPM2 依赖性钙内流似乎特别有趣，因为它参与调节屏障功能、细胞死亡、细胞迁移和血管生成。这些功能的任何损伤都可能导致动脉粥样硬化或高血压等疾病中观察到的内皮功能障碍。因此，TRPM2 似乎是与活性氧物质产生增加相关疾病的有吸引力的治疗靶点。然而，在能够应用 TRPM2 抑制剂之前，需要解决一些问题。主要问题是缺乏特异性、膜通透性差和体内条件下稳定性低。本文旨在总结 TRPM2 在内皮细胞中的作用的最新发现。我们还展示了 TRPM2 抑制剂在心血管系统疾病中的应用的一些未来展望。
