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Int. J. Mol. Sci. 2017, 18(4), 854; doi:10.3390/ijms18040854

Thioredoxin-Interacting Protein Mediates Apoptosis in Early Brain Injury after Subarachnoid Haemorrhage

Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
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Academic Editor: Christo Christov
Received: 20 February 2017 / Revised: 11 April 2017 / Accepted: 13 April 2017 / Published: 18 April 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Early 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
Keywords: thioredoxin-interacting protein; subarachnoid haemorrhage; early brain injury; apoptosis; protein kinase RNA-like ER kinase thioredoxin-interacting protein; subarachnoid haemorrhage; early brain injury; apoptosis; protein kinase RNA-like ER kinase
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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.

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