Overexpression of cellular prion protein alters postischemic Erk1/2 phosphorylation but not Akt phosphorylation and protects against focal cerebral ischemia.
Overexpression of cellular prion protein alters postischemic Erk1/2 phosphorylation but not Akt phosphorylation and protects against focal cerebral ischemia.
复制标题
细胞朊病毒蛋白的过度表达会改变缺血后 Erk1/2 磷酸化，但不会改变 Akt 磷酸化，并可预防局灶性脑缺血。
DOI：
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发表时间：
2008
影响因子：
2.8
通讯作者：
M. Bähr
中科院分区：
文献类型：
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作者：
J. Weise;T. Doeppner;T. Müller;A. Wrede;W. Schulz;I. Zerr;O. Witte;M. Bähr
目的
细胞朊蛋白（PrPC）的生理功能尚不清楚。越来越多的证据表明，PrPC具有神经保护特性，其缺失增加了对局灶性脑缺血的易感性。本研究的目的是阐明PrPC过表达在体内缺血性脑损伤中的作用。
方法
对PrPC过表达（TG 35）和野生型（WT）小鼠进行90分钟的短暂局灶性脑缺血，随后在损伤后24小时进行梗塞体积分析。为了确定PrPC过表达对调节缺血性细胞死亡的重要信号通路的影响，我们使用定量Western Blot分析研究了缺血后Akt和Erk 1/2的激活和表达。
结果
TG 35小鼠显示出明显较小的梗死体积，并显示出减少早期缺血后Erk 1/2磷酸化，这是一种已知加剧短暂脑缺血后神经元损伤的途径。相比之下，PrPC过表达没有改变缺血后Akt磷酸化，其作用是抗凋亡，并在PrPC敲除动物中减少。
结论
这些结果表明，PrPC过表达减少有害的Erk 1/2激活，但不影响Akt激活短暂脑缺血后，提示不同的胞质信号通路在PrPC介导的神经保护的作用。
PURPOSE
The physiological function of the cellular prion protein (PrPC) is still unclear. A growing body of evidence suggests that PrPC has neuroprotective properties and that its deletion increases susceptibility to focal cerebral ischemia. The purpose of this study was to elucidate the role of PrPC overexpression in ischemic brain injury in vivo.
METHODS
PrPC overexpressing (TG35) and wild type (WT) mice were subjected to a 90-minute transient focal cerebral ischemia followed by infarct volume analysis 24 hours after lesion. To identify effects of PrPC overexpression on signalling pathways important for the regulation of ischemic cell death, we studied postischemic activation and expression of Akt and Erk1/2 using quantitative Western Blot analysis.
RESULTS
TG35 mice displayed significantly smaller infarct volumes and showed reduced early postischemic Erk1/2 phosphorylation, a pathway known to exacerbate neuronal injury following transient cerebral ischemia. In contrast, PrPC overexpression did not change postischemic Akt phosphorylation, which acts anti-apoptotic and is reduced in PrPC knockout animals.
CONCLUSIONS
These results demonstrate that PrPC overexpression reduces deleterious Erk1/2 activation but does not affect Akt activation after transient cerebral ischemia, suggesting a role for distinct cytosolic signalling pathways in PrPC mediated neuroprotection.