Nong Xiting, Li Nan, Wang Xiang, Li Heng, Wu Xiaoping, Li Ming, Hao Wenqing, Yang Guang
Department of Endocrinology, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
Department of Radiology, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
J Clin Biochem Nutr. 2023 Sep;73(2):131-137. doi: 10.3164/jcbn.22-104. Epub 2023 Aug 11.
The tripartite motif 62 is an E3 ubiquitin ligase protein that regulates cellular processes, including differentiation, immunity, development and apoptosis, leading to various disease states, such as cancer and inflammatory diseases. However, the role and mechanism of the tripartite motif 62 in the process of diabetic-induced cognitive impairment have not been reported. Therefore, the aim of this study was to investigate the role and mechanism of the tripartite motif 62 in diabetic-induced cognitive impairment. The results showed that the expression of the tripartite motif 62 was up-regulated in diabetic mice. Silencing of TRIM62 increased body weight and decreased fasting blood glucose in diabetic mice. In addition, knockdown of the tripartite motif 62 inhibited STZ-induced inflammation, apoptosis and oxidative stress. Further studies showed that the TLR4/NF-κB pathway and NLRP3 inflammasomes were involved in the regulation of diabetic mice by the tripartite motif 62. More importantly, inhibition of the tripartite motif 62 improved cognitive impairment and learning ability in mice. In conclusion, inhibition of TRIM62 inhibits STZ-induced inflammation, cell apoptosis and oxidative stress, and improves the cognitive ability of mice. Therefore, the tripartite motif 62 may be an important target for the treatment of diabetes-induced cognitive impairment.
三重基序62是一种E3泛素连接酶蛋白，可调节包括分化、免疫、发育和细胞凋亡在内的细胞过程，导致各种疾病状态，如癌症和炎症性疾病。然而，三重基序62在糖尿病诱导的认知障碍过程中的作用和机制尚未见报道。因此，本研究的目的是探讨三重基序62在糖尿病诱导的认知障碍中的作用和机制。结果显示，三重基序62在糖尿病小鼠中的表达上调。沉默TRIM62可增加糖尿病小鼠的体重并降低空腹血糖。此外，敲低三重基序62可抑制链脲佐菌素诱导的炎症、细胞凋亡和氧化应激。进一步研究表明，TLR4/NF-κB信号通路和NLRP3炎性小体参与了三重基序62对糖尿病小鼠的调控。更重要的是，抑制三重基序62可改善小鼠的认知障碍和学习能力。总之，抑制TRIM62可抑制链脲佐菌素诱导的炎症、细胞凋亡和氧化应激，并提高小鼠的认知能力。因此，三重基序62可能是治疗糖尿病诱导的认知障碍的重要靶点。
