Neurotoxicity induced by glutamate (Glu) is often used to study the signaling mechanism of neurological disorders. The identification of specific genetic factors that cause Glu-induced neurotoxicity provides evidence for the common pathways of neuronal apoptosis and inflammation. TRIM27 has been found to induce apoptosis and inflammation. Nevertheless, there is little evidence that TRIM27 is associated with Glu-induced neurotoxicity. We found that TRIM27 expression was increased in epilepsy patients and in HT22 cells following Glu treatment. Glu-mediated cell apoptosis, decreased PPARγ expression, and increased levels of cleaved Caspase-3 and IL-1β expression in HT22 cells were significantly inhibited by TRIM27 knockdown. TRIM27 overexpression significantly induced cell apoptosis and expression of cleaved Caspase-3 and IL-1β, but inhibited PPARγ expression in HT22 cells, which were reversed by ROZ, suggesting the involvement of PPARγ in TRIM27-mediated cell apoptosis and inflammation in HT22 cells. Mechanically, TRIM27 ubiquitinates and degrades PPARγ, following induces cleaved Caspase-3 and IL-1β expression. Clinically, increased expression of TRIM27 in epilepsy patients was associated with decreased PPARγ expression. Taken together, our study suggests that TRIM27-mediated ubiquitination of PPARγ promotes Glu-induced HT22 cell apoptosis and IL-1β release.

谷氨酸 (Glu) 诱导的神经毒性通常用于研究神经系统疾病的信号传导机制。导致 Glu 诱导的神经毒性的特定遗传因素的鉴定为神经元凋亡和炎症的常见途径提供了证据。已发现 TRIM27 可诱导细胞凋亡和炎症。然而，几乎没有证据表明 TRIM27 与 Glu 诱导的神经毒性有关。我们发现癫痫患者和 Glu 治疗后 HT22 细胞中的 TRIM27 表达增加。TRIM27 敲低可显着抑制 HT22 细胞中 Glu 介导的细胞凋亡、PPARγ 表达降低以及裂解的 Caspase-3 和 IL-1β 表达水平升高。TRIM27 过表达显着诱导细胞凋亡和裂解 Caspase-3 和 IL-1β 的表达，但抑制了 HT22 细胞中 PPARγ 的表达，这被 ROZ 逆转，表明 PPARγ 参与了 TRIM27 介导的 HT22 细胞凋亡和炎症。在机械上，TRIM27 泛素化并降解 PPARγ，随后诱导裂解的 Caspase-3 和 IL-1β 表达。临床上，癫痫患者中 TRIM27 表达的增加与 PPARγ 表达的降低有关。总之，我们的研究表明，TRIM27 介导的 PPARγ 泛素化促进了 Glu 诱导的 HT22 细胞凋亡和 IL-1β 释放。癫痫患者中 TRIM27 表达的增加与 PPARγ 表达的降低有关。总之，我们的研究表明，TRIM27 介导的 PPARγ 泛素化促进了 Glu 诱导的 HT22 细胞凋亡和 IL-1β 释放。癫痫患者中 TRIM27 表达的增加与 PPARγ 表达的降低有关。总之，我们的研究表明，TRIM27 介导的 PPARγ 泛素化促进了 Glu 诱导的 HT22 细胞凋亡和 IL-1β 释放。