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Downregulation of UBE2Q1 is associated with neuronal apoptosis in rat brain cortex following traumatic brain injury
Authors:Baoying Hu  Huifei Zou  Aihong Li  Aihang Guo  Junkang Jiang
Affiliation:1. Medical College, Nantong University, Nantong, People's Republic of China;2. Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China;3. School of Public Health, Nantong University, Nantong, People's Republic of China
Abstract: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.
Keywords:UBE2Q1  traumatic brain injury  neuronal apoptosis  p53  rat
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