Department of Emergency, SSL Central Hospital of Dongguan City, 1 Xianglong Road, Dongguan, 523326, Guangdong, People's Republic of China.
J Bioenerg Biomembr. 2023 Jun;55(3):207-217. doi: 10.1007/s10863-023-09968-5. Epub 2023 Jun 2.
Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel, was significantly upregulated in the blood of patients with sepsis. This study focuses on the preliminary exploration of the probable regulatory mechanism of TRPM7 in sepsis-induced myocardial injury (SIMI). HL-1 cardiac muscle cell line was treated with lipopolysaccharide (LPS) to mimic SIMI in vitro, and TRPM7 level was assessed. The impacts of TRPM7 knockdown on cellular inflammation response, oxidative stress, apoptosis, endoplasmic reticulum (ER) stress, and ferroptosis were identified. In order to explore the mechanism, ER stress agonist tunicamycin (TM) or ferroptosis inducer erastin was applied to treat HL-1 cells. The influences of TM and erastin on the aforementioned aspects were evaluated. TRPM7 was elevated in response to LPS stimulation, and its knockdown reduced the secretion of inflammatory factors and oxidative stress degree. Moreover, TRPM7 knockdown significantly suppressed cell apoptosis, ER stress, and ferroptosis. TM and erastin reversed the functions of TRPM7 knockdown, indicating ER stress and ferroptosis mediated in the regulation of TRPM7. This research proposes the possibility of TRPM7 as a marker or target for SIMI, and provides theoretical support for follow-up research.
瞬时受体电位 melastatin 7（TRPM7）是一种非选择性阳离子通道，在脓毒症患者的血液中显著上调。本研究主要探讨 TRPM7 在脓毒症诱导的心肌损伤（SIMI）中可能的调控机制。采用脂多糖（LPS）处理 HL-1 心肌细胞系模拟 SIMI，检测 TRPM7 水平。研究 TRPM7 敲低对细胞炎症反应、氧化应激、细胞凋亡、内质网（ER）应激和铁死亡的影响。为了探讨其机制，用 ER 应激激动剂衣霉素（TM）或铁死亡诱导剂 erastin 处理 HL-1 细胞。评估 TM 和 erastin 对上述方面的影响。LPS 刺激可导致 TRPM7 上调，其敲低可减少炎症因子的分泌和氧化应激程度。此外，TRPM7 敲低显著抑制细胞凋亡、ER 应激和铁死亡。TM 和 erastin 逆转了 TRPM7 敲低的作用，表明 ER 应激和铁死亡介导了 TRPM7 的调控。本研究提出了 TRPM7 作为 SIMI 标志物或靶点的可能性，为后续研究提供了理论支持。
