Department of Emergency, First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Department of Emergency, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, China.
Cell Mol Neurobiol. 2021 Mar;41(2):341-351. doi: 10.1007/s10571-020-00855-w. Epub 2020 Apr 25.
Tripartite motif-containing 22 (TRIM22) has been documented to participate in numerous cellular activities during human diseases. However, whether TRIM22 is involved in the regulation of neuronal survival during the progression of cerebral ischemia/reperfusion (I/R) injury remains unknown. In the present study, treatment of HCN-2 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) markedly upregulated TRIM22 expression. A significant increase in TRIM22 expression was observed in the ischemic cortex tissues from middle cerebral artery occlusion/reperfusion mice. OGD/R inhibited the viability and induced the apoptosis of HCN-2 cells, which was accompanied by an increase in caspase-3 activity and an increase in LDH release. Furthermore, OGD/R increased the levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, and monocyte chemoattractant protein-1 and induced NLRP3 inflammasome activation, as evidenced by increases in NACHT, LRR and PYD domains-containing protein 3, apoptosis-associated speck-like protein containing a caspase recruitment domain and cleaved caspase-1 expression and caspase-1 activity. However, these changes induced by OGD/R were blocked by silencing of TRIM22. In addition, TRIM22 regulated NF-κB activity in HCN-2 cells undergoing OGD/R stimulation. Furthermore, inhibition of NF-κB by pyrrolidine dithiocarbamate inhibited OGD/R-induced NLRP3 inflammasome activation in HCN-2 cells. Taken together, silencing of TRIM22 protects neurons against OGD/R-induced apoptosis and inflammation. The anti-inflammatory effect of TRIM22 knockdown was the consequence of inhibition of NF-κB/NLRP3 axis. TRIM22 may be a potential target for treating cerebral I/R injury.
三结构域蛋白 22（TRIM22）已被证明参与人类疾病过程中的多种细胞活动。然而，TRIM22 是否参与脑缺血/再灌注（I/R）损伤过程中神经元存活的调节尚不清楚。在本研究中，用氧葡萄糖剥夺/复氧（OGD/R）处理 HCN-2 细胞可显著上调 TRIM22 的表达。在大脑中动脉闭塞/再灌注小鼠的缺血皮质组织中观察到 TRIM22 表达的显著增加。OGD/R 抑制 HCN-2 细胞的活力并诱导其凋亡，同时伴随着 caspase-3 活性的增加和 LDH 释放的增加。此外，OGD/R 增加了肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6 和单核细胞趋化蛋白-1 的水平，并诱导 NLRP3 炎性体激活，表现为 NACHT、LRR 和 PYD 结构域包含蛋白 3、含衔接蛋白募集结构域的凋亡相关斑点样蛋白和裂解的 caspase-1 的表达和 caspase-1 活性的增加。然而，OGD/R 诱导的这些变化被沉默 TRIM22 所阻断。此外，TRIM22 调节 HCN-2 细胞在 OGD/R 刺激下的 NF-κB 活性。此外，NF-κB 的抑制剂吡咯烷二硫代氨基甲酸酯抑制了 HCN-2 细胞中 OGD/R 诱导的 NLRP3 炎性体激活。综上所述，沉默 TRIM22 可保护神经元免受 OGD/R 诱导的凋亡和炎症。TRIM22 敲低的抗炎作用是抑制 NF-κB/NLRP3 轴的结果。TRIM22 可能是治疗脑 I/R 损伤的潜在靶点。
