In a previous study, we observed the effect of phosphoglycerate mutase 1 (PGAM1) on proliferating cells and neuroblasts in the subgranular zone of mouse dentate gyrus. In the present study, we examined the roles of PGAM1 in the HT22 hippocampal cell line and in gerbil hippocampus after H2O2-induced oxidative stress and after ischemia/reperfusion, respectively. Control-PGAM1 and Tat-PGAM1 proteins were synthesized using Tat-1 expression vector since Tat-1 fusion proteins can easily cross the blood-brain barrier and cell membranes. We found that transduction of Tat-PGAM1 protein into HT22 cells was dose- and time-dependent. Delivery of the protein to the cytoplasm was confirmed by western blotting and immunocytochemistry. Treatment of HT22 cells with Tat-PGAM1 protein showed a concentration-dependent reduction in cell damage and decreased formation of reactive oxygen species after H2O2 exposure. Tat-PGAM1 administration significantly ameliorated the ischemia-induced hyperactivity in gerbils at 1 day after ischemia/reperfusion. Additionally, a pronounced decrease in neuronal damage and reactive gliosis were observed in the hippocampal CA1 region of the Tat-PGAM1-treated group at 4 days after ischemia/reperfusion compared to that in the vehicle (Tat peptide) or control-PGAM1-treated groups. Administration of Tat-PGAM1 mitigated the changes in ATP content, succinate dehydrogenase activity, pH, and 4-hydroxynonenal levels in the hippocampus at 4 and 7 days after ischemia/reperfusion compared to that in the vehicle-treated group. In addition, administration of Tat-PGAM1 significantly ameliorated the ischemia-induced increases of lactate levels in the hippocampus at 15 min and 6 h after ischemia/reperfusion than in the vehicle or control-PGAM1-treated groups. These results suggest that Tat-PGAM1 can be used as a therapeutic agent to prevent neuronal damage from oxidative stress or ischemia.

中文翻译：

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磷酸甘油酸突变酶1通过促进能量利用来减少缺血/再灌注后海马中的神经元损伤。

在以前的研究中，我们观察到磷酸甘油酸突变酶1（PGAM1）对小鼠齿状回亚颗粒区增殖细胞和成神经细胞的影响。在本研究中，我们分别研究了H2O2诱导的氧化应激和缺血/再灌注后PGAM1在HT22海马细胞系和沙鼠海马中的作用。使用Tat-1表达载体合成了Control-PGAM1和Tat-PGAM1蛋白，因为Tat-1融合蛋白可以轻松穿过血脑屏障和细胞膜。我们发现，Tat-PGAM1蛋白转导进入HT22细胞是剂量和时间依赖性的。通过蛋白质印迹和免疫细胞化学证实了蛋白质向细胞质的递送。用Tat-PGAM1蛋白处理HT22细胞后，H2O2暴露后细胞损伤的浓度依赖性降低，而活性氧的形成减少。Tat-PGAM1给药可显着改善缺血/再灌注后1天缺血诱导的沙土鼠多动症。此外，与溶媒（Tat肽）或对照组-PGAM1处理组相比，在缺血/再灌注后4天，在Tat-PGAM1处理组的海马CA1区观察到神经元损伤和反应性神经胶质细胞减少明显。与溶媒治疗组相比，在缺血/再灌注后第4天和第7天，给予Tat-PGAM1可减轻海马中ATP含量，琥珀酸脱氢酶活性，pH和4-羟基壬烯水平的变化。此外，与溶媒或对照组PGAM1处理组相比，给予Tat-PGAM1可以显着改善缺血/再灌注后15分钟和6小时的局部缺血诱导的海马乳酸水平增加。这些结果表明，Tat-PGAM1可用作预防氧化应激或缺血引起的神经元损伤的治疗剂。