Mol Cell Biochem. 2019 Jan;450(1-2):149-158. doi: 10.1007/s11010-018-3381-1. Epub 2018 Jun 15.

Thioredoxin-interacting protein mediates mitochondrion-dependent apoptosis in early brain injury after subarachnoid hemorrhage.

Liang Y1, Che X1, Zhao Q1, Darwazeh R1, Zhang H1, Jiang D1, Zhao J1, Xiang X1, Qin W1, Liu L1, He Z2.

Author information

1Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.2Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. geno_he@163.com.

Abstract

Early brain injury (EBI) was reported to be the primary cause of high mortality and poor outcomes in subarachnoid hemorrhage (SAH) patients, and apoptosis is regarded as the most important physiopathologic mechanism during EBI. Recently, our team found that thioredoxin-interacting protein (TXNIP) links endoplasmic reticulum stress (ER stress) to neuronal apoptosis and aggravates EBI. However, the other underlying mechanisms remain unknown. Mitochondria are considered to be the central points in integrating apoptotic cell death. However, whether crosstalk between TXNIP and the mitochondria-mediated intrinsic apoptotic pathway is effective on EBI has not been previously reported. Therefore, we created an endovascular perforation SAH model in Sprague-Dawley rats to determine the possible mechanism. We found that TXNIP expression in apoptotic neurons significantly increased in the SAH group compared with the sham group. In addition, increased TXNIP expression was accompanied by remarkable changes in mitochondrial-related antiapoptotic and proapoptotic factors. Furthermore, resveratrol (RES, a TXNIP inhibitor) administration significantly downregulated the expression of TXNIP and mitochondria-related proapoptotic factors. Additionally, it attenuated SAH prognostic indicators, such as brain edema, blood-brain barrier permeability, and neurological deficits. Therefore, our study further confirms that TXNIP may participate in neuronal apoptosis through the mitochondrial signaling pathway and that TXNIP may be a target for SAH treatment.

KEYWORDS:

Apoptosis; Early brain injury; Mitochondria; Subarachnoid hemorrhage; Thioredoxin-interacting protein

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