p38MAPK regulation of transcription factor targets in muscle and heart of the hibernating bat, Myotis lucifugus
p38MAPK regulation of transcription factor targets in muscle and heart of the hibernating bat, Myotis lucifugus
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DOI：
10.1002/cbf.1416
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发表时间：
2007-11-01
影响因子：
3.6
通讯作者：
Storey, Kenneth B.
中科院分区：
文献类型：
--
作者：
Eddy, Sean F.;Storey, Kenneth B.
哺乳动物冬眠结合了一个深刻的净代谢率抑制与选择性上调的关键基因，其蛋白质产物解决特定的代谢需要的冬眠。参与调控冬眠应答基因表达的信号转导途径和转录因子是人们感兴趣的研究课题。本研究表明，p38丝裂原活化蛋白激酶（p38（MAPK））和选择的下游转录因子（CREB，ATF-2，麋鹿-1）在冬眠期间的骨骼肌代谢反应的小棕蝠，鼠耳蝠lucifugus的重要作用。蛋白质印迹法被用来量化的总蛋白和水平的磷酸化，活性形式的p38（MARK），CREB，ATF-2和麋鹿-1在骨骼肌和心脏的常温和冬眠蝙蝠。在心脏中，p38（MAPK）通路在麻痹期间没有明显激活，但骨骼肌在麻痹状态与唤醒状态相比，磷酸化p38（T180/YI 82）、CREBS 133、ATF-（2 T69/71）和Elk-1（S383）的量显示出强烈的增加（2.2-11倍）。相比之下，在冬眠期间，心脏中Elk-1的总水平和磷酸化水平都降低到仅为正常体温值的30%。这些数据暗示p38（MAPK）及其转录因子靶点CREB、ATF-2和Elk-1在冬眠期间骨骼肌维持中的作用。版权所有（C）2007约翰威利父子有限公司
Mammalian hibernation combines a profound net metabolic rate suppression with the selective up-regulation of key genes whose protein products address specific metabolic needs of the hibernator. The signal transduction pathways and transcription factors involved in regulating hibernation-responsive gene expression are of great interest. The present study suggests an important role for the p38 mitogen-activated protein kinase (p38(MAPK)) and selected downstream transcription factors under its control (CREB, ATF-2, Elk-1) in the metabolic response by skeletal muscle during hibernation of little brown bats, Myotis lucifugus. Western blotting was used to quantify both total protein and levels of the phosphorylated, active forms of p38(MARK), CREB, ATF-2 and Elk-1 in both skeletal muscle and heart of euthermic and hibernating bats. The p38(MAPK) pathway was not apparently activated in heart during torpor but skeletal muscle showed strong increases (2.2-11-fold) in the amounts of phosphorylated p38(T180/YI82), CREBS133, ATF-(2T69/71) and Elk-1(S383) in the torpid versus aroused state. By contrast both total and phosphorylated levels of Elk-1 in heart were reduced during hibernation to just 30% of the euthermic values. These data implicate p38(MAPK) and its transcription factor targets, CREB, ATF-2 and Elk-1 in skeletal muscle maintenance during hibernation. Copyright (C) 2007 John Wiley & Sons, Ltd.