Thioredoxin-Interacting Protein Mediates Apoptosis in Early Brain Injury after Subarachnoid Haemorrhage
AbstractEarly brain injury (EBI) is considered to be the major factor associated with high morbidity and mortality after subarachnoid haemorrhage (SAH). Apoptosis is the major pathological mechanism of EBI, and its pathogenesis has not been fully clarified. Here, we report that thioredoxin-interacting protein (TXNIP), which is induced by protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK), participates in EBI by promoting apoptosis. By using adult male Sprague-Dawley rats to establish SAH models, as well as Terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining, immunofluorescence, and western blot, we found that TXNIP expression significantly increased after SAH in comparison to the sham group and peaked at 48 h (up to 3.2-fold). Meanwhile, TXNIP was widely expressed in neurons and colocalized with TUNEL-positive cells in the hippocampus and cortex of SAH rats. After administration of TXNIP inhibitor-resveratrol (60 mg/kg), TXNIP small interfering RNA (siRNA) and the PERK inhibitor GSK2656157, TXNIP expression was significantly reduced, accompanied by an attenuation of apoptosis and prognostic indicators, including SAH grade, neurological deficits, brain water content, and blood-brain barrier (BBB) permeability. Collectively, these results suggest that TXNIP may participate in EBI after SAH by mediating apoptosis. The blockage of TXNIP induced by PERK could be a potential therapeutic strategy for SAH treatment. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 1875 KB)
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
Zhao, Q.; Che, X.; Zhang, H.; Tan, G.; Liu, L.; Jiang, D.; Zhao, J.; Xiang, X.; Sun, X.; He, Z. Thioredoxin-Interacting Protein Mediates Apoptosis in Early Brain Injury after Subarachnoid Haemorrhage. Int. J. Mol. Sci. 2017, 18, 854.
Zhao Q, Che X, Zhang H, Tan G, Liu L, Jiang D, Zhao J, Xiang X, Sun X, He Z. Thioredoxin-Interacting Protein Mediates Apoptosis in Early Brain Injury after Subarachnoid Haemorrhage. International Journal of Molecular Sciences. 2017; 18(4):854.Chicago/Turabian Style
Zhao, Qing; Che, Xudong; Zhang, Hongxia; Tan, Guanping; Liu, Liu; Jiang, Dengzhi; Zhao, Jun; Xiang, Xiang; Sun, Xiaochuan; He, Zhaohui. 2017. "Thioredoxin-Interacting Protein Mediates Apoptosis in Early Brain Injury after Subarachnoid Haemorrhage." Int. J. Mol. Sci. 18, no. 4: 854.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.