TT01001 attenuates oxidative stress and neuronal apoptosis by preventing mitoNEET-mediated mitochondrial dysfunction after subarachnoid hemorrhage in rats

被引:15
|
作者
Shi, Guangyao [1 ]
Cui, Lei [2 ]
Chen, Rui [3 ]
Liang, Shaodong [4 ]
Wang, Chunlei [5 ]
Wu, Pei [5 ]
机构
[1] Nanchang Univ, Queen Mary Coll, Nanchang, Jiangxi, Peoples R China
[2] Harbin Med Univ, Dept Nephrol, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China
[3] Heilongjiang Farms & Land Reclamat Beian Adm, Dept Neurol, Cent Hosp, Beian, Peoples R China
[4] Mudanjiang Med Univ, Dept Neurosurg, Hongqi Hosp, Mudanjiang, Peoples R China
[5] Harbin Med Univ, Dept Neurosurg, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China
基金
黑龙江省自然科学基金; 中国国家自然科学基金;
关键词
apoptosis; early brain injury; mitochondrial dysfunction; oxidative stress; subarachnoid hemorrhage; EARLY BRAIN-INJURY;
D O I
10.1097/WNR.0000000000001492
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Oxidative stress and neuronal apoptosis are considered crucial therapeutic targets against early brain injury (EBI) after subarachnoid hemorrhage (SAH). Emerging evidence indicates that mitochondrial dysfunction is the main reason for oxidative stress and neuronal apoptosis. MitoNEET, an outer mitochondrial membrane protein, has been shown to regulate mitochondrial function. However, whether mitoNEET activation attenuates oxidative stress and neuronal apoptosis after SAH remains unknown. This study was therefore conducted to verify the neuroprotective role of mitoNEET in EBI after SAH in rats. A total of 93 rats were subjected to an endovascular perforation model of SAH. TT01001, a selective agonist of mitoNEET, was administered intraperitoneally 1 h after SAH induction. Neurological tests, immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining, dihydroergotamine (DHE) staining, and western blot experiments were performed. The results showed that MitoNEET is expressed in neurons, but significantly decreased at 24 h after SAH induction. Activating mitoNEET with TT01001 significantly improved the neurological deficits, and reduced oxidative stress and neuronal apoptosis as measured by DHE and TUNEL staining, when compared with the SAH+vehicle group. Furthermore, TT01001 treatment decreased the expression of the proapoptotic marker, Bax, while increasing the expression of the antiapoptotic marker, Bcl-2. Together, our results suggested that mitoNEET activation with TT01001 reduced oxidative stress injury and neuronal apoptosis by improving mitochondrial dysfunction in EBI after SAH.
引用
收藏
页码:845 / 850
页数:6
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