title: Up-regulation of GBP2 is Associated with Neuronal Apoptosis in Rat Brain Cortex Following Traumatic Brain Injury.
abstract: 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 H2O2-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.
authors.affiliation: Department of Education and Science, The Second Peoples' Hospital of Nantong, Nantong, Jiangsu Province, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Miao
authors.affiliation: ICU, The Second Peoples' Hospital of Nantong, Nantong, Jiangsu Province, China.
authors.forename: Meihong
authors.initials: M
authors.lastname: Ge
authors.affiliation: ICU, Affiliated of Nantong University, Nantong, Jiangsu Province, China. HLLfy123456@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D000070642:Brain Injuries, Traumatic / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C086640:Gbp2 protein, rat; D019204:GTP-Binding Proteins
keywords: Apoptosis; GBP2; P-Stat1; Traumatic brain injury