| First Author | Sui X | Year | 2021 |
| Journal | Exp Neurol | Volume | 339 |
| Pages | 113642 | PubMed ID | 33600816 |
| Mgi Jnum | J:307700 | Mgi Id | MGI:6706977 |
| Doi | 10.1016/j.expneurol.2021.113642 | Citation | Sui X, et al. (2021) Neuroprotective roles of HAX-1 in ischemic neuronal injury. Exp Neurol 339:113642 |
| abstractText | Hematopoietic cell-specific protein 1 associated protein X-1 (HAX-1) is a novel mitochondrial protein that regulates oxidative stress-induced apoptosis. However, the roles of HAX-1 in ischemic neuronal injury have not been thoroughly elucidated. In this study, the expression and roles of HAX-1 after ischemic stress were investigated using in vivo and in vitro models. The effect of oxidative stress on the regulation of HAX-1 was examined using knockout mice lacking nicotinamide-adenine dinucleotide phosphate oxidase 2 (NOX2), which is a major source of reactive oxygen species (ROS) after cerebral ischemia. Male C57BL/6 J mice were subjected to transient forebrain ischemia induced by 22-min occlusion of the bilateral common carotid arteries, and striatum samples were analyzed. For in vitro ischemic experiments, oxygen and glucose deprivation (OGD) in a rat pheochromocytoma cell line was utilized. Western blotting and immunofluorescence analysis revealed HAX-1 expression in neuronal mitochondria, which was significantly decreased after ischemia in vivo and in vitro. In NOX2 knockout mice, ischemia-induced decrease in HAX-1 expression and ischemic neuronal injury was significantly alleviated compared to those in wild-type mice. Inhibition of HAX-1 using small interfering RNA significantly increased injury in cultured cells after OGD. These findings suggest that HAX-1 has a neuroprotective effect against ischemic neuronal injury, and downregulation of HAX-1 by NOX2-produced ROS induces apoptosis after cerebral ischemia. |
