CART attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion

被引：51

作者：

Qiu, Bin ^{[1
]}

Hu, Shengdi ^{[1
]}

Liu, Libing ^{[2
]}

Chen, Man ^{[1
]}

Wang, Lai ^{[1
]}

Zeng, Xianwei ^{[2
]}

Zhu, Shigong ^{[1
]}

机构：

[1] Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100191, Peoples R China

[2] Weifang Med Univ, Dept Anesthesiol, Weifang, Shandong, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2013年 / 436卷 / 04期

基金：

中国国家自然科学基金;

关键词：

CART; BDNF; CREB; Cerebral ischemia; Endoplasmic reticulum stress; Neuron; NEUROTROPHIC FACTOR; ERK ACTIVATION; CELL-DEATH; STROKE; BRAIN; TRANSCRIPT; PROTECTS; NEUROPROTECTION; EXPRESSION; CASPASE-12;

D O I：

10.1016/j.bbrc.2013.05.142

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：655 / 659

页数：5

共 24 条

[1]

Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12 [J].