期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 436, 期 4, 页码 655-659出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.05.142
关键词
CART; BDNF; CREB; Cerebral ischemia; Endoplasmic reticulum stress; Neuron
资金
- National Natural Science Foundation of China [81171081]
- Research Fund for the Doctoral Program of Higher Education [20090001110060]
- Major National Basic Research Grant of China [2010CB912504]
Cocaine and amphetamine regulated transcript (CART), a neuropeptide, has shown strong neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury in vivo and in vitro. Here, we report a new effect of CART on ER stress which is induced by cerebral I/R in a rat model of middle cerebral artery occlusion (MCAO) or by oxygen and glucose deprivation (OGD) in cultured cortical neurons, as well as a new functionality of BDNF in the neuroprotection by CART against the ER stress in cerebral I/R. The results showed that CART was effective in reducing the neuronal apoptosis and expression of ER stress markers (GRP78, CHOP and cleaved caspase12), and increasing the BDNF expression in I/R injury rat cortex both in vivo and in vitro. In addition, the effects of CART on ischemia-induced neuronal apoptosis and ER stress were suppressed by tyrosine receptor kinase B (TrkB) IgG, whereas the effects of CART on BDNF transcription, synthesis and secretion were abolished by CREB siRNA. This work suggests that CART is functional in inhibiting the cerebral I/R-induced ER stress and neuronal apoptosis by facilitating the transcription, synthesis and secretion of BDNF in a CREB-dependent way. (c) 2013 Elsevier Inc. All rights reserved.
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