期刊
NEUROSCIENCE LETTERS
卷 507, 期 2, 页码 118-123出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2011.11.058
关键词
Hypoxia-ischemia; Mammalian target of rapamycin; Hypoxia-inducible factor-1 alpha; Vascular endothelial growth factor; Apoptosis
资金
- National Natural Science Foundation of China [30825039, 31171020, 30973236, 81172174]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT0935]
The mammalian target of rapamycin (mTOR) exerts neuroprotective effects under hypoxic or ischemic conditions. To explore whether mTOR participates in neuroprotective signaling through regulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF) and neuronal apoptosis in developing rat brain with hypoxia-ischemia (HI), we operated on postnatal day 10 rats by ligating the common carotid artery followed by exposure to systemic hypoxia. Brains were collected at various intervals to detect the expression of mTOR, phosphorylated mTOR (p-mTOR), HIF-1 alpha, VEGF and cleaved caspase 3 (CC3), using immunohistochemistry and Western blot analysis. We also used terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) to detect neuronal apoptosis. The p-mTOR protein expression increased at 2 h after HI, peaked at 8 h, lasted 24 h, and then dropped to the basal level. Also, the expression of HIF-1 alpha and VEGF was significantly enhanced and peaked at 8 h after HI. Up-regulated expression of CC3 was observed at 2 h, peaked at 24 h, and lasted 72 h after HI. Increased neuronal apoptosis is associated with reduced HIF-1 alpha and VEGF expression. Furthermore, pretreatment with rapamycin, a mTOR specific inhibitor, significantly inhibited HIF-1 alpha and VEGF protein after HI. The expression of CC3 and the number of TUNEL-positive cells were up-regulated at 8 h and down-regulated at 24 h after HI in the rapamycin-treated group. Our findings suggest that mTOR may participate in the regulation of HIF-1 alpha, VEGF and neuronal apoptosis, serving neuroprotective functions after HI in developing rat brain. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据