Zinc finger protein 667 expression is upregulated by cerebral ischemic preconditioning and protects cells from oxidative stress

Abstract

Abstract. 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 (H 2 O 2 ) 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 H 2 O 2 treatment, whereas ZNF667 gene overexpression significantly improved cell viability following H 2 O 2 treatment. These results suggested that ZNF667 plays a neuroprotective role by acting as a transcription factor in cerebral IPC.

lncRNA ZNF667‐AS1 (NR_036521.1) inhibits the progression of colorectal cancer via regulating ANK2/JAK2 expression

“…ZNF667 is a member of the zinc finger protein C2H2 family, which was initially found to be significantly overexpressed in myocardial ischemia tissues (Lei et al, 2007;Yuan, Huang, Yuan, Zhao, & Jiang, 2013). Zhao et al (2017) stated that the low-expressed lncRNA ZNF667-AS1 is an independent prognostic factor for CRC and inhibits the proliferation of CRC cells.…”

ZNF667 Serves as a Putative Oncogene in Human Hepatocellular Carcinoma

“…Being a member of C2H2 zinc finger protein family, Zinc finger protein 667 (ZNF667) was initially found to be a significantly over-expressed protein during myocardial ischemic preconditioning [11, 12]. Enhancing expression of ZNF667 can inhibit the apoptosis via inhibiting Bax and Fas expression [13, 14].…”

Aberrant hypermethylation-mediated downregulation of antisense lncRNA ZNF667-AS1 and its sense gene ZNF667 correlate with progression and prognosis of esophageal squamous cell carcinoma

“…ZNF667 is a novel zinc finger protein, which was found to be upregulated by myocardial ischemic preconditioning (IPC); and it played a neuroprotective role by acting as a transcription factor in cerebral IPC 25 . ZNF667 was also detected to inhibit the expression and the promoter activity of the rat proapoptotic gene Bax gene, and at the same time prevented apoptosis of H9c2 cells, induced by H2O2 and Dox 26 .…”