Downregulation of BACH1 Protects AGAINST Cerebral Ischemia/Reperfusion Injury through the Functions of HO-1 and NQO1

  • Neuroscience. 2020 Jun 1:436:154-166. doi: 10.1016/j.neuroscience.2020.04.014.
Shan Yu  1 ,  Jingjie Zhai  2 ,  Jing Yu  3 ,  Qiwei Yang  4 ,  Jinghui Yang  5
Affiliations
  • 1. Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130033, People's Republic of China.
  • 2. Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun 130021, People's Republic of China.
  • 3. Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun 130033, People's Republic of China.
  • 4. Central Laboratory, The Second Hospital of Jilin University, Changchun 130041, People's Republic of China.
  • 5. Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, People's Republic of China. Electronic address: [email protected].
PMID: 32311410 DOI: 10.1016/j.neuroscience.2020.04.014
Abstract

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.

Keywords
BACH1; apoptosis; cerebral ischemia/reperfusion injury; oxidative stress.
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