2-(4-Methoxyphenyl) ethyl-2-acetamido-2-deoxy-β-D-pyranoside confers neuroprotection in cell and animal models of ischemic stroke through calpain1/PKA/CREB-mediated induction of neuronal glucose transporter 3
2-(4-Methoxyphenyl) ethyl-2-acetamido-2-deoxy-β-D-pyranoside confers neuroprotection in cell and animal models of ischemic stroke through calpain1/PKA/CREB-mediated induction of neuronal glucose transporter 3
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2-(4-甲氧基苯基)乙基-2-乙酰氨基-2-脱氧-β-D-吡喃糖苷通过钙蛋白酶1/PKA/CREB介导的神经元葡萄糖转运蛋白3的诱导，在缺血性中风的细胞和动物模型中提供神经保护作用
DOI：
10.1016/j.taap.2014.03.025
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发表时间：
2014-06-15
影响因子：
3.8
通讯作者：
Ding, Fei
中科院分区：
文献类型：
--
作者：
Yu, Shu;Cheng, Qiong;Ding, Fei
红景天苷是一种天然的神经保护剂，其类似物2-（4-甲氧基苯基）乙基-2-乙酰氨基-2-脱氧-β-D-吡喃糖苷（SalA-4 g）已在本实验室合成。在这项研究中，我们表明，SalA-4 g促进神经元的存活和抑制神经元凋亡的原代海马神经元暴露于氧和葡萄糖剥夺（OGD）和大鼠缺血短暂大脑中动脉闭塞（MCAO），分别，和SalA-4 g是更神经保护比红景天苷。我们进一步发现，SalA-4g增加了OGD损伤的原代海马神经元的葡萄糖摄取，并增加了缺血脑中葡萄糖转运蛋白3（GLUT 3）的表达和募集。信号转导分析显示，SalA-4 g可激活OGD损伤海马神经元CREB的磷酸化，增加PM Rh的表达，而H-89抑制PKA/CREB可减轻OGD损伤海马神经元葡萄糖摄取和GLUT 3表达的增加，阻断SalA-4 g的保护作用。此外，SalA-4 g可抑制OGD损伤的原代海马神经元胞内Ca ~（2+）内流和calpain 1的激活。我们的研究结果表明，SalA-4 g的神经保护作用可能是通过增加葡萄糖摄取和升高GLUT 3的表达，通过calpain 1/PKA/CREB途径。(C)2014爱思唯尔公司All rights reserved.
Salidroside is proven to be a neuroprotective agent of natural origin, and its analog, 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-beta-D-pyranoside (named SalA-4 g), has been synthesized in our lab. In this study, we showed that SalA-4 g promoted neuronal survival and inhibited neuronal apoptosis in primary hippocampal neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to ischemia by transient middle cerebral artery occlusion (MCAO), respectively, and that SalA-4 g was more neuroprotective than salidroside. We further found that SalA-4g elevated glucose uptake in OGD-injured primary hippocampal neurons and increased the expression and recruitment of glucose transporter 3 (GLUT3) in ischemic brain. Signaling analysis revealed that SalA-4 g triggered the phosphorylation of CREB, and increased the expression of PM Rh in primary hippocampal neurons exposed to OGD injury, while inhibition of PKA/CREB by H-89 alleviated the elevation in glucose uptake and GLUT3 expression, and blocked the protective effects of SalA-4 g. Moreover, SalA-4 g was noted to inhibit intracellular Ca2+ influx and calpain1 activation in OGD-injured primary hippocampal neurons. Our results suggest that SalA-4 g neuroprotection might be mediated by increased glucose uptake and elevated GLUT3 expression through calpain1/PKA/CREB pathway. (C) 2014 Elsevier Inc. All rights reserved.