Activation of ERK and Akt signaling in focal cerebral ischemia:: Modulation by TGF-α and involvement of NMDA receptor
Activation of ERK and Akt signaling in focal cerebral ischemia:: Modulation by TGF-α and involvement of NMDA receptor
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DOI：
10.1006/nbdi.2002.0553
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发表时间：
2002-12-01
影响因子：
6.1
通讯作者：
Planas, AM
中科院分区：
文献类型：
--
作者：
Friguls, B;Petegnief, V;Planas, AM
脑缺血激活ERK和Akt通路。我们研究了这些激活是否受到保护性生长因子转化生长因子-α（TGF-α）治疗的影响，以及它们是否通过N-甲基D-天冬氨酸（NMDA）受体介导。将大鼠大脑中动脉闭塞，1小时后研究信号传导。非竞争性NMDA受体拮抗剂MK-801在闭塞前腹腔注射，而在其他大鼠中，TGF-α在闭塞前后脑室注射。缺血引起ERK磷酸化的细胞核，定位在内皮细胞和神经元。ERK的磷酸化被TGF-α阻止，但在细胞核和细胞质中被MK-801增强。此外，MK-801而不是TGF-α增加p-Akt。结果表明，防止ERK激活与TGF-α的保护作用有关，而MK-801的保护作用与促生存Akt的激活有关。虽然结果支持NMDA受体信号传导排除Akt激活，但我们没有发现证据支持它是缺血诱导的ERK磷酸化的基础。这项研究表明，神经保护的结果从死亡和生存信号通路之间的良好平衡。(C)2003 Elsevier Science（美国）。
Cerebral ischemia activates ERK and Akt pathways. We studied whether these activations were affected by treatment with the protective growth factor transforming growth factor-alpha (TGF-alpha), and whether they were mediated through N-methyl D-aspartate (NMDA) receptors. The middle cerebral artery was occluded in rats and signaling was studied 1 h later. Noncompetitive NMDA receptor antagonist MK-801 was injected i.p. before the occlusion, whereas in other rats TGF-alpha was given intraventricularly before and after occlusion. Ischemia caused ERK phosphorylation in the nucleus, localized in the endothelium and neurons. Phosphorylation of ERK was prevented by TGF-alpha, but it was enhanced in the nucleus and cytoplasm by MK-801. Also, MK-801 but not TGF-a increased p-Akt. Results suggest that preventing ERK activation is related to the protective effect of TGF-alpha, whereas the protective effect of MK-801 is associated with activation of pro-survival Akt. While results support that NMDA receptor signaling precludes Akt activation, we did not find evidence to support that it underlies ischemia-induced ERK phosphorylation. This study illustrates that neuroprotection results from a fine balance between death and survival signaling pathways. (C) 2003 Elsevier Science (USA).