Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8286330 | Redox Biology | 2018 | 15 Pages |
Abstract
Cellular oxidative stress plays a vital role in the pathological process of neural damage in cerebral ischemia/reperfusion (I/R). The breast cancer susceptibility protein 1 (BRCA1), a tumor suppressor, can modulate cellular antioxidant response and DNA repair. Yet the role of BRCA1 in cerebral I/R injury has not been explored. In this study, we observed that BRCA1 was mainly expressed in neurons and was up-regulated in response to I/R insult. Overexpression of BRCA1 attenuated reactive oxygen species production and lipid peroxidation. Enhanced BRCA1 expression promoted DNA double strand break repair through non-homologous end joining pathway. These effects consequently led to neuronal cell survival and neurological recovery. Mechanically, BRCA1 can interact with the nuclear factor (erythroid-derived 2)-like 2 (NRF2) through BRCA1 C-terminal (BRCT) domain. The cross-talk between BRCT and NRF2 activated the NRF2/Antioxidant Response Element signaling pathway and thus protected injured neurons during cerebral I/R. In conclusion, enhanced BRCA1 after cerebral I/R injury may attenuate or prevent neural damage from I/R via NRF2-mediated antioxidant pathway. The finding may provide a potential therapeutic target against ischemic stroke.
Keywords
CA1BRCA1 C-terminalGPX3GPx4BRCTGCLMGCLCDSBsDcxCaMKIIBERGFPGFAPcornu Ammonis 1amyotrophic lateral sclerosisAlzheimer diseaseALSbase excision repairCNSdoublecortincentral nervous systemdouble strand breaksAREGlial fibrillary acidic proteingreen fluorescent proteincalcium/calmodulin-dependent protein kinase IIBRCA1Glutathione peroxidase 3glutathione peroxidase 4
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Authors
Pengfei Xu, Qian Liu, Yi Xie, Xiaolei Shi, Yunzi Li, Mengna Peng, Hongquan Guo, Rui Sun, Juanji Li, Ye Hong, Xinfeng Liu, Gelin Xu,