Downregulation of UBE2Q1 is associated with neuronal apoptosis in rat brain cortex following traumatic brain injury
Downregulation of UBE2Q1 is associated with neuronal apoptosis in rat brain cortex following traumatic brain injury
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UBE2Q1 下调与脑外伤后大鼠大脑皮层神经元凋亡相关
DOI：
10.1002/jnr.23305
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发表时间：
2014-01
影响因子：
4.2
通讯作者：
Jiang Junkang
中科院分区：
文献类型：
--
作者：
Wan Chunhua;Chen Jian;Hu Baoying;Zou Huifei;Li Aihong;Guo Aihang;Jiang Junkang
泛素蛋白酶体系统 (UPS) 的异常功能与各种神经系统疾病的病理学有关。尽管据报道，各种 UPS 成分的表达在创伤性脑损伤 (TBI) 后发生了显着改变，但有关该主题的详细信息仍不清楚。在这项研究中，我们利用微阵列检测发现了一个编码泛素结合酶 E2Q1 (UBE2Q1) 的基因，该基因在 TBI 期间显着下调。蛋白质印迹和免疫组织化学分析证实，与对侧和假手术组相比，病变部位附近的同侧大脑皮层中 UBE2Q1 的表达降低。双重免疫荧光染色显示UBE2Q1主要在神经元细胞核中表达，少数在正常皮质星形胶质细胞中表达。此外，我们观察到脑外伤后 UBE2Q1 阳性神经元的数量显着减少。此外，我们发现 TBI 导致大脑皮层中 p53、bax、p21 和活性 caspase 3 的水平显着增加，这与 UBE2Q1 表达下降相关。我们还发现UBE2Q1的敲除明显增加了p53的水平，而过表达UBE2Q1则减弱了PC12神经元细胞中的p53水平。因此，干扰 UBE2Q1 会增强 H2O2 诱导的 PC12 细胞凋亡。综上所述，我们的研究结果表明，UBE2Q1 可能通过调节 p53 信号传导在 TBI 的神经病理过程中发挥重要作用。 © 2013 Wiley 期刊公司。
Aberrant functionality of the ubiquitin proteasome system (UPS) has been implicated in the pathology of various neurological disorders. Although it has been reported that the expressions of various UPS components were altered significantly following traumatic brain injury (TBI), detailed information on the subject remains largely unclear. In the study, using microarray assay, we identified a gene encoding ubiquitin‐conjugating enzyme E2Q1 (UBE2Q1) that was significantly downregulated during TBI. Western blot and immunohistochemical analyses verified the reduced expression of UBE2Q1 in ipsilateral brain cortex adjacent to the lesion site compared with the contralateral and sham‐operated ones. Double‐immunofluorescence staining indicated that UBE2Q1 was expressed mainly in the nucleus of neurons, with a minority in astrocytes in normal cortex. In addition, we observed a remarkable reduction in the number of UBE2Q1‐positive neurons following brain trauma. Furthermore, we showed that TBI resulted in a significant increase in the levels of p53, bax, p21 and active caspase 3 in brain cortex, which was correlated with decreased expression of UBE2Q1. We also found that knockdown of UBE2Q1 apparently increased the level of p53, whereas overexpressing UBE2Q1 attenuated cellular p53 level in PC12 neuronal cells. Accordingly, interference with UBE2Q1 augmented H2O2‐induced apoptosis of PC12 cells. Taken together, our findings indicate that UBE2Q1 might play an important role in the neuropathological process of TBI through modulating p53 signaling. © 2013 Wiley Periodicals, Inc.
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影响因子：
2.9
作者：
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通讯作者：
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影响因子：
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作者：
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