Breast cancer susceptibility protein 1 (BRCA1) rescues neurons from cerebral ischemia/reperfusion injury through NRF2-mediated antioxidant pathway

Redox Biology
Pengfei XuGelin Xu

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.

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Citations

Mar 21, 2019·Journal of Cellular and Molecular Medicine·Lingbo KongDingjun Hao
Dec 22, 2019·Brain Sciences·Masanori KuriharaAtsushi Iwata
Mar 21, 2020·Frontiers in Molecular Neuroscience·Liquan WuLijuan Gu
Nov 4, 2020·The Journal of Clinical Investigation·Yi XieXinfeng Liu
Aug 11, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Dai-Qiang LiuDa-Wei Ye
Aug 4, 2021·Molecular and Cellular Neurosciences·Vien NguyenYerem Yeghiazarians
Sep 1, 2021·Journal of Neuroinflammation·Pengfei XuWei Hu

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Methods Mentioned

BETA
transfection
MDA
dissection
electrophoresis
Assay
PCR
pull-down
Protein Assay
nuclear translocation

Software Mentioned

SPSS
Image J
Image
maze
Pro Plus
comet assay software project ( CASP )
ANY

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