Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injury
Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injury
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DOI：
10.1111/j.1460-9568.2007.05720.x
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Dietrich, W. Dalton
中科院分区：
文献类型：
--
作者：
Atkins, Coleen M.;Oliva, Anthony A., Jr.;Dietrich, W. Dalton
创伤性脑损伤(TBI)导致明显的海马区病理改变和海马依赖性记忆丧失，低温治疗可减轻这两种情况。为阐明低温对大鼠颅脑损伤后的分子调控机制，采用大鼠中度矢状旁液冲击性脑损伤模型。脑温度在伤前30min和伤后4h内维持在常温或低温状态。用Western blotting检测同侧海马区。我们发现低温可增强细胞外信号调节蛋白1/2(ERK1/2)及其下游效应蛋白P90核糖体S6激酶(P90RSK)和转录因子cAMP反应元件结合蛋白。另一种p90RSK底物Bad的磷酸化也随着低温的增加而增加。ERK1/2通过丝裂原活化蛋白激酶相互作用蛋白1(Mnk1)和翻译因子真核细胞起始因子4E(EIF4E)的磷酸化来调节mRNA的翻译。低温还增强了Mnk1和eIF4E的磷酸化。增强ERK1/2的激活及其下游信号通路可能是亚低温治疗改善脑损伤后功能转归的分子机制之一。
Traumatic brain injury (TBI) results in significant hippocampal pathology and hippocampal-dependent memory loss, both of which are alleviated by hypothermia treatment. To elucidate the molecular mechanisms regulated by hypothermia after TBI, rats underwent moderate parasagittal fluid-percussion brain injury. Brain temperature was maintained at normothermic or hypothermic temperatures for 30 min prior and up to 4 h after TBI. The ipsilateral hippocampus was assayed with Western blotting. We found that hypothermia potentiated extracellular signal-regulated kinase 1/2 (ERK1/2) activation and its downstream effectors, p90 ribosomal S6 kinase (p90RSK) and the transcription factor cAMP response element-binding protein. Phosphorylation of another p90RSK substrate, Bad, also increased with hypothermia after TBI. ERK1/2 regulates mRNA translation through phosphorylation of mitogen-activated protein kinase-interacting kinase 1 (Mnk1) and the translation factor eukaryotic initiation factor 4E (eIF4E). Hypothermia also potentiated the phosphorylation of both Mnk1 and eIF4E. Augmentation of ERK1/2 activation and its downstream signalling components may be one molecular mechanism that hypothermia treatment elicits to improve functional outcome after TBI.