| First Author | Yu S | Year | 2020 |
| Journal | Neuroscience | Volume | 436 |
| Pages | 154-166 | PubMed ID | 32311410 |
| Mgi Jnum | J:293150 | Mgi Id | MGI:6445760 |
| Doi | 10.1016/j.neuroscience.2020.04.014 | Citation | Yu S, et al. (2020) Downregulation of BACH1 Protects AGAINST Cerebral Ischemia/Reperfusion Injury through the Functions of HO-1 and NQO1. Neuroscience 436:154-166 |
| abstractText | Cerebral ischemia/reperfusion (I/R) usually leads to the exacerbation of brain injury. In the present research, the effect of BTB and CNC homology 1 (BACH1) on cerebral I/R injury was studied. Mice model of middle cerebral artery occlusion/reperfusion (MCAO/R) and Neuro-2a (N2a) cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) were established to investigate the role of BACH1. It was found that MCAO/R mice expressed much higher BACH1 in the brain tissues accompanied with severe cerebral infarction, whereas downregulation of BACH1 reduced the infarction in MCAO/R mice. TUNEL staining showed that the downregulation of BACH1 inhibited apoptosis in brain tissues of MCAO/R mice. The expression of cleaved caspase-3 and cleaved PARP were also decreased by the downregulation of BACH1. Reactive oxygen species (ROS) and 3-nitrotyrosine (3-NT) staining showed that the downregulation of BACH1 reduced the levels of ROS and 3-NT. Moreover, less malondialdehyde (MDA) and more superoxide dismutase (SOD), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were detected in MCAO/R mice pretreated with BACH1 shRNA, indicating that the downregulation of BACH1 reduced the oxidative stress. Similar conclusions were obtained from the further studies on N2a cells of OGD/R. We found that the downregulation of BACH1 reduced cell damage, oxidative stress and apoptosis in N2a cells. It was also demonstrated that the downregulation of BACH1 functioned through HO-1 and NQO1, which played important roles in protecting against cerebral I/R injury. Thus, BACH1 might be a potential therapeutic target for preventing cerebral I/R injury. |
