Department of Neurology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou 563003, P.R. China.
Exp Anim. 2023 Nov 9;72(4):475-489. doi: 10.1538/expanim.23-0019. Epub 2023 Jun 1.
Epilepsy is the most common chronic disorder in the nervous system, mainly characterized by recurrent, periodic, unpredictable seizures. Post-translational modifications (PTMs) are important protein functional regulators that regulate various physiological and pathological processes. It is significant for cell activity, stability, protein folding, and localization. Phosphoglycerate kinase (PGK) 1 has traditionally been studied as an important adenosine triphosphate (ATP)-generating enzyme of the glycolytic pathway. PGK1 catalyzes the reversible transfer of a phosphoryl group from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP, producing 3-phosphoglycerate (3-PG) and ATP. In addition to cell metabolism regulation, PGK1 is involved in multiple biological activities, including angiogenesis, autophagy, and DNA repair. However, the exact role of PGK1 succinylation in epilepsy has not been thoroughly investigated. The expression of PGK1 succinylation was analyzed by Immunoprecipitation. Western blots were used to assess the expression of PGK1, angiostatin, and vascular endothelial growth factor (VEGF) in a rat model of lithium-pilocarpine-induced acute epilepsy. Behavioral experiments were performed in a rat model of lithium-pilocarpine-induced acute epilepsy. ELISA method was used to measure the level of S100β in serum brain biomarkers' integrity of the blood-brain barrier. The expression of the succinylation of PGK1 was decreased in a rat model of lithium-pilocarpine-induced acute epilepsy compared with the normal rats in the hippocampus. Interestingly, the lysine 15 (K15), and the arginine (R) variants of lentivirus increased the susceptibility in a rat model of lithium-pilocarpine-induced acute epilepsy, and the K15 the glutamate (E) variants, had the opposite effect. In addition, the succinylation of PGK1 at K15 affected the expression of PGK1 succinylation but not the expression of PGK1total protein. Furthermore, the study found that the succinylation of PGK1 at K15 may affect the level of angiostatin and VEGF in the hippocampus, which also affects the level of S100β in serum. In conclusion, the mutation of the K15 site of PGK1 may alter the expression of the succinylation of PGK1 and then affect the integrity of the blood-brain barrier through the angiostatin / VEGF pathway altering the activity of epilepsy, which may be one of the new mechanisms of treatment strategies.
癫痫是神经系统最常见的慢性疾病，主要表现为反复发作、周期性、不可预测的癫痫发作。翻译后修饰（PTMs）是重要的蛋白质功能调节剂，调节各种生理和病理过程。它对细胞活动、稳定性、蛋白质折叠和定位都很重要。磷酸甘油酸激酶（PGK）1 一直被研究为糖酵解途径中重要的三磷酸腺苷（ATP）生成酶。PGK1 催化 1,3-双磷酸甘油酸（1,3-BPG）向 ADP 的磷酸基团可逆转移，生成 3-磷酸甘油酸（3-PG）和 ATP。除了细胞代谢调节外，PGK1 还参与多种生物学活性，包括血管生成、自噬和 DNA 修复。然而，PGK1 琥珀酰化在癫痫中的确切作用尚未被彻底研究。通过免疫沉淀分析 PGK1 琥珀酰化的表达。Western blot 用于评估锂-匹罗卡品诱导的急性癫痫大鼠模型中 PGK1、血管抑素和血管内皮生长因子（VEGF）的表达。在锂-匹罗卡品诱导的急性癫痫大鼠模型中进行行为实验。酶联免疫吸附试验（ELISA）法用于测量血清脑生物标志物中 S100β 水平，以评估血脑屏障的完整性。与正常大鼠相比，锂-匹罗卡品诱导的急性癫痫大鼠模型中海马中 PGK1 琥珀酰化的表达降低。有趣的是，慢病毒的赖氨酸 15（K15）和精氨酸（R）变体增加了锂-匹罗卡品诱导的急性癫痫大鼠模型的易感性，而 K15 谷氨酸（E）变体则产生相反的效果。此外，PGK1 在 K15 处的琥珀酰化影响 PGK1 琥珀酰化的表达，但不影响 PGK1 总蛋白的表达。此外，研究发现 PGK1 在 K15 处的琥珀酰化可能会影响海马中血管抑素和 VEGF 的水平，这也会影响血清中 S100β 的水平。总之，PGK1 的 K15 位点突变可能会改变 PGK1 琥珀酰化的表达，然后通过血管抑素/VEGF 通路影响血脑屏障的完整性，改变癫痫的活性，这可能是治疗策略的新机制之一。
