Tissue-type plasminogen activator mediates neuroglial coupling in the central nervous system.
Tissue-type plasminogen activator mediates neuroglial coupling in the central nervous system.
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DOI：
10.1016/j.neuroscience.2013.10.060
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发表时间：
2014-01-17
期刊：
影响因子：
3.3
通讯作者：
Yepes, M.
中科院分区：
文献类型：
--
作者：
An, J.;Haile, W. B.;Wu, F.;Torre, E.;Yepes, M.
关键词：
神经元、星形胶质细胞和内皮细胞之间的相互作用起着将能量供应与神经元活动变化耦合的核心作用。长期以来，人们认为葡萄糖是神经元能量的唯一来源。然而，越来越多的实验证据表明，由血管周围星形胶质细胞有氧糖酵解产生的乳酸也是神经元活动的能量来源，特别是当血管内空间的葡萄糖供应中断时。腺苷一磷酸活化蛋白激酶（AMPK）是一种进化上保守的激酶，其通过诱导葡萄糖摄取和激活糖酵解途径将细胞活性与能量消耗偶联。血脑屏障（BBB）对葡萄糖的摄取是由转运蛋白GLUT 1介导的，GLUT 1在内皮细胞和星形胶质细胞终末足过程中大量表达。组织型纤溶酶原激活物（tPA）是一种丝氨酸蛋白酶，存在于内皮细胞、星形胶质细胞和神经元中。神经元tPA的遗传过表达或用重组tPA（rtPA）处理保护神经元免受代谢应激或兴奋性毒性的有害影响，这是通过独立于tPA将纤溶酶原切割成纤溶酶的能力的机制实现的。这里提出的工作表明，暴露于代谢应激诱导tPA从神经元，但不是从星形胶质细胞的快速释放。这种tPA诱导AMPK活化、GLUT 1的膜募集和GLUT 1介导的星形胶质细胞和内皮细胞中的葡萄糖摄取。我们的数据表明，这是由星形胶质细胞的乳酸的合成和释放，并通过单羧酸转运蛋白-2（MCT-2）的这种乳酸的摄取促进暴露于代谢应激的神经元的存活。
The interaction between neurons, astrocytes and endothelial cells plays a central role coupling energy supply with changes in neuronal activity. For a long time it was believed that glucose was the only source of energy for neurons. However, a growing body of experimental evidence indicates that lactic acid, generated by aerobic glycolysis in perivascular astrocytes, is also a source of energy for neuronal activity, particularly when the supply of glucose from the intravascular space is interrupted. Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved kinase that couples cellular activity with energy consumption via induction of the uptake of glucose and activation of the glycolytic pathway. The uptake of glucose by the blood-brain barrier (BBB) is mediated by the transporter GLUT1, which is abundantly expressed in endothelial cells and astrocytic end-feet processes. Tissue-type plasminogen activator (tPA) is a serine proteinase that is found in endothelial cells, astrocytes and neurons. Genetic overexpression of neuronal tPA or treatment with recombinant tPA (rtPA) protects neurons from the deleterious effects of metabolic stress or excitotoxicity, via a mechanism independent of tPA’s ability to cleave plasminogen into plasmin. The work presented here shows that exposure to metabolic stress induces the rapid release of tPA from neurons but not from astrocytes. This tPA induces AMPK activation, membrane recruitment of GLUT1, and GLUT1-mediated glucose uptake in astrocytes and endothelial cells. Our data indicate that this is followed by the synthesis and release of lactic acid from astrocytes, and that the uptake of this lactic acid via the monocarboxylate transporter-2 (MCT-2) promotes survival in neurons exposed to metabolic stress.
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影响因子：
6.3
作者：
Bak, Lasse K.;Schousboe, Arne;Waagepetersen, Helle S.
通讯作者：
Waagepetersen, Helle S.
影响因子：
5.3
作者：
Bushong, EA;Martone, ME;Ellisman, MH
通讯作者：
Ellisman, MH
影响因子：
15.9
作者：
Yepes, M;Sandkvist, M;Lawrence, DA
通讯作者：
Lawrence, DA
DOI：
10.1073/pnas.91.22.10625
发表时间：
1994-10-25
影响因子：
11.1
作者：
PELLERIN, L;MAGISTRETTI, PJ
通讯作者：
MAGISTRETTI, PJ
影响因子：
56.9
作者：
FOX, PT;RAICHLE, ME;DENCE, C
通讯作者：
DENCE, C