Brain ischemic injury is associated with clinical emergencies such as acute ischemic and hemorrhagic stroke, head trauma, prolonged severe hypotension and cardiac arrest. Ischemic preconditioning (IPC) is the most powerful endogenous mechanism against ischemic injury. However, the majority of IPC treatments are invasive and thus impractical in the clinical setting. Identifying the endogenous neuroprotective mechanism induced by IPC is important for developing new strategies to reduce stroke severity. Zinc finger protein 667 (ZNF667) is a novel zinc finger protein that is upregulated by myocardial IPC. However, its functional role in neuronal ischemia has not been elucidated. In this study, the changes of ZNF667 expression on cerebral IPC and its potential neuroprotective function were investigated. The cerebral ischemia model was established by ameliorated four‑vessel occlusion in rats. The northern blot results demonstrated that ZNF667 expression was increased in the hippocampus and cortex at 12 and 24 h after cerebral ischemic pretreatment. To investigate the neuroprotective function of ZNF667, enhanced green fluorescent protein (EGFP)‑ZNF667 fusion protein was expressed in C2C12 and brain astrocytoma cells and its subcellular localization was detected by confocal microscopy. EGFP‑ZNF667 fusion proteins were localized in the nucleus of C2C12 and brain astrocytoma cells, indicating that ZNF667 may act as a transcription factor in neural cells. To mimic oxidative stress associated with ischemia/reperfusion injury, hydrogen peroxide (H2O2) was used to treat cells. Cell viability was measured by the lactate dehydrogenase (LDH) and WST‑1 assays. A decrease in viability was detected in C2C12 and astrocytoma cells following H2O2 treatment, whereas ZNF667 gene overexpression significantly improved cell viability following H2O2 treatment. These results suggested that ZNF667 plays a neuroprotective role by acting as a transcription factor in cerebral IPC.

Related Articles