Zhang Jing, Han Ying, Zhao Yang, Li Qin-Rui, Jin Hong-Fang, Du Jun-Bao, Qin Jiong
Department of Pediatrics, Peking University First Hospital Beijing, PR China.
Department of Pediatrics, Peking University People's Hospital Beijing, PR China.
Int J Clin Exp Pathol. 2019 Feb 1;12(2):599-605. eCollection 2019.
TRIB3 (tribblespseudokinase 3) is a pseudokinase that affects several cellular functions, and its expression is increased during endoplasmic reticulum stress (ER stress). How recurrent seizures affect the regulation of TRIB3 in the hippocampus during epilepsy remains unclear. In this study, we investigated the role of TRIB3 in the kainic acid (KA)-induced seizures and related brain injury. In a rat model of kainic acid-induced seizures, neuronal excitotoxic injury and apoptosis, and increases in the expression of TRIB3 and ER stress markers glucose-regulated protein 78 (GRP78) and C/EBP homologous binding protein (CHOP) were observed in the hippocampus by 24 h to 30 d after KA administration. Furthermore, phosphorylation of AKT, which is inhibited by TRIB3, was decreased in the hippocampus after KA-evoked seizure. These results indicate that ER stress, TRIB3 and AKT signaling are involved in the acute and prolonged hippocampal injury following KA induced seizure, suggesting that the ER stress-associated gene TRIB3 plays an important role in neuronal apoptosis after seizure.
TRIB3（ Tribbles假激酶3）是一种影响多种细胞功能的假激酶，在内质网应激（ER应激）期间其表达会增加。癫痫发作期间反复癫痫发作如何影响海马体中TRIB3的调节仍不清楚。在本研究中，我们研究了TRIB3在海藻酸（KA）诱导的癫痫发作及相关脑损伤中的作用。在海藻酸诱导的癫痫发作大鼠模型中，在给予KA后24小时至30天，海马体中观察到神经元兴奋性毒性损伤和凋亡，以及TRIB3和ER应激标志物葡萄糖调节蛋白78（GRP78）和C/EBP同源结合蛋白（CHOP）的表达增加。此外，KA诱发癫痫发作后，海马体中被TRIB3抑制的AKT磷酸化水平降低。这些结果表明，ER应激、TRIB3和AKT信号通路参与了KA诱导癫痫发作后的急性和长期海马体损伤，提示ER应激相关基因TRIB3在癫痫发作后的神经元凋亡中起重要作用。
