Hypothermia produces rat liver proteomic changes as in hibernating mammals but decreases endoplasmic reticulum chaperones
Hypothermia produces rat liver proteomic changes as in hibernating mammals but decreases endoplasmic reticulum chaperones
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DOI：
10.1016/j.cryobiol.2012.05.004
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发表时间：
2012-10-01
期刊：
影响因子：
2.7
通讯作者：
Matsumoto, Ken-ichi
中科院分区：
文献类型：
--
作者：
Oda, Teiji;Shimizu, Kouji;Matsumoto, Ken-ichi
低温在临床上用于在主动脉/复杂先天性心脏手术或复苏后脑病期间保护脑等器官免受缺血损伤。低温保护的主要机制是抑制新陈代谢，然而，降温的多效性作用尚不完全清楚。在这里，我们使用了一个大鼠模型系统来评估深低温引起的代谢变化。用基于荧光的二维差示凝胶电泳(DGE)和基质辅助激光解吸/电离飞行时间(MALDI-TOF/TOF)串联质谱仪鉴定低温诱导的变化。将大鼠随机分为常温对照组(37℃，n=6)和亚低温组(23℃，n=6)。作为基因本体论(GO)术语和途径的丰富分析，差异表达蛋白质的功能图谱被执行。我们发现，深低温麻醉大鼠肝脏内质网和线粒体的蛋白质以及参与ATP结合、氨基酸代谢和尿素循环的蛋白质、氧化应激反应、抗细胞凋亡、细胞凋亡负性调节的蛋白质均显著下调。除了内质网伴侣外，低温大鼠蛋白质组的变化与其他正在冬眠的哺乳动物的蛋白质组变化相似。(C)2012 Elsevier Inc.保留所有权利。
Hypothermia is used in the clinic for protection of organs such as the brain against ischemic injury during aortic/complex congenital cardiac surgery or post-resuscitation encephalopathy. The principal mechanism of hypothermic protection is suppression of metabolism, however, the pleiotropic effects of cooling are incompletely understood. Here, we used a rat model system to evaluate metabolic changes induced by deep hypothermia. The hypothermia-induced changes were identified using fluorescence-based two-dimensional (2-D) difference gel electrophoresis (DIGE) and matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF/TOF) tandem mass spectrometry. Rats were randomly assigned to a normothermic control group (37 degrees C, n = 6) or hypothermia group (23 degrees C, n = 6) that received surface cooling for 3 h. Liver tissue was excised for assessment. Functional profiling of differently expressed proteins was performed as an enrichment analysis of Gene Ontology (GO) terms and pathways. We found that the livers of anesthetized rats with deep hypothermia showed significant downregulation of proteins in the endoplasmic reticulum and mitochondria, and of those involved in ATP binding, amino acid metabolism and urea cycle, response to oxidative stress, anti-apoptosis, negative regulation of apoptosis. The changes in the proteome of the hypothermic rats showed similarities, except with regard to endoplasmic reticulum chaperones, to those identified elsewhere in mammals undergoing hibernation. (C)2012 Elsevier Inc. All rights reserved.