Miao Qi, Ge Meihong, Huang Lili
Department of Education and Science, The Second Peoples' Hospital of Nantong, Nantong, Jiangsu Province, China.
ICU, The Second Peoples' Hospital of Nantong, Nantong, Jiangsu Province, China.
Neurochem Res. 2017 May;42(5):1515-1523. doi: 10.1007/s11064-017-2208-x. Epub 2017 Feb 27.
Guanylate binding protein 2 (GBP2) is one member of GBP family. Recently, GBP2 has been proposed to be a novel target of anti-cancer drugs. However, the role of GBP2 in the traumatic brain injury (TBI) is very limited. In this study, we sought to define GBP2's role in brain injury. GBP2 protein levels were significantly increased in the brain 3 days after injury, suggesting a functional role for GBP2 in TBI. Neuronal cells overexpressing GBP2 exhibited up-regulation of co-location of GBP2 and NeuN following TBI, suggesting that GBP2 potentiates the neuron apoptosis. To confirm the role of GBP2 in neuron apoptosis process, we employed a highly potent inhibitor of GBP2 (GBP2 RNAi). In HO-stimulated PC12 cells, in vitro blockade of GBP2 activity using GBP2 RNAi markedly attenuated the neuron apoptosis number. GBP2 RNAi also inhibited the expression levels of active caspase3 and p-Stat1. Furthermore, we found the expression of p-Stat1 in line with GBP2 and GBP2 interacted with p-Stat1 following TBI. The Jak2 inhibitor, AG490 inhibited this interaction and decreased the active caspase3 expression as well as promoted the functional recovery. Taken together, these data suggest that GBP2 RNAi has a protective effect in a rat TBI. This study demonstrates that GBP2 is an important positive regulator of TBI and is a promising therapeutic target for brain injury.
鸟苷酸结合蛋白2（GBP2）是GBP家族的成员之一。最近，GBP2被认为是抗癌药物的一个新靶点。然而，GBP2在创伤性脑损伤（TBI）中的作用非常有限。在本研究中，我们试图确定GBP2在脑损伤中的作用。损伤后3天，大脑中GBP2蛋白水平显著升高，提示GBP2在TBI中具有功能作用。过表达GBP2的神经元细胞在TBI后GBP2与NeuN的共定位上调，提示GBP2增强神经元凋亡。为了证实GBP2在神经元凋亡过程中的作用，我们使用了一种高效的GBP2抑制剂（GBP2 RNAi）。在HO刺激的PC12细胞中,使用GBP2 RNAi体外阻断GBP2活性可显著减少神经元凋亡数量。GBP2 RNAi还抑制了活性caspase3和p-Stat1的表达水平。此外，我们发现p-Stat1的表达与GBP2一致，且TBI后GBP2与p-Stat1相互作用。Jak2抑制剂AG490抑制了这种相互作用，降低了活性caspase3的表达，并促进了功能恢复。综上所述，这些数据表明GBP2 RNAi对大鼠TBI具有保护作用。本研究表明，GBP2是TBI的重要正调节因子，是脑损伤有前景的治疗靶点。
