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内毒素血症期间心肌蛋白质变化的蛋白质组学分析

Proteomics analysis of changes in myocardial proteins during endotoxemia.

作者信息

Robichaud Sophie, Lalu Manoj, Udenberg Tanner, Schulz Richard, Sawicki Grzegorz

机构信息

Department of Pathology and Laboratory Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada.

出版信息

J Proteomics. 2009 May 2;72(4):648-55. doi: 10.1016/j.jprot.2009.01.010.

DOI:10.1016/j.jprot.2009.01.010
PMID:19367682
Abstract

Marked contractile failure of the heart is important in both sepsis and endotoxemia, and an understanding of its molecular basis is lacking. We investigated changes in rat myocardial proteins in endotoxemia. Rats were injected with lipopolysaccharide (LPS) and sacrificed 3, 6, 12 and 24 h later. Control rats were injected with a vehicle and sacrificed 6 h later.In the LPS-6 h and LPS-12 h groups, plasma nitrites (NO(x)(-)), were elevated while mean arterial blood pressure (MAP) was depressed as compared to the controls. In the LPS-24 h group, plasma (NO(x)(-)) was returning to the base level whereas MAP was still decreased in comparison to the control group. Six proteins showed changes between groups. All six proteins were decreased in abundance in the LPS-6 h group vs. control. Of the six proteins, three were normalized in the LPS-24 h group: albumin, heat shock protein 27 and triosephosphate isomerase. The three other did not normalize: glyceraldehyde 3-phosphate dehydrogenase, H+-transporting ATP synthase and dienoyl-CoA isomerase. A decrease in abundance of metabolic enzymes may be the result of mitochondrial damage and this decrease could play a protective role against the hypermetabolic state associated with the later stages of sepsis and endotoxemia.

摘要

明显的心脏收缩功能衰竭在脓毒症和内毒素血症中都很重要,而对其分子基础的了解尚缺。我们研究了内毒素血症大鼠心肌蛋白的变化。给大鼠注射脂多糖(LPS),并在3、6、12和24小时后处死。对照大鼠注射赋形剂并在6小时后处死。与对照组相比,LPS-6小时和LPS-12小时组的血浆亚硝酸盐(NO(x)(-))升高,而平均动脉血压(MAP)降低。在LPS-24小时组,血浆(NO(x)(-))恢复到基础水平,而与对照组相比MAP仍降低。六组蛋白在各实验组间表现出变化。与对照组相比,LPS-6小时组的所有六种蛋白丰度均降低。在这六种蛋白中,三种在LPS-24小时组恢复正常:白蛋白、热休克蛋白27和磷酸丙糖异构酶。另外三种未恢复正常:甘油醛-3-磷酸脱氢酶、H +转运ATP合酶和二烯酰辅酶A异构酶。代谢酶丰度的降低可能是线粒体损伤的结果,这种降低可能对脓毒症和内毒素血症后期相关的高代谢状态起到保护作用。

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引用本文的文献

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Circ Heart Fail. 2015 Sep;8(5):988-96. doi: 10.1161/CIRCHEARTFAILURE.115.002383. Epub 2015 Aug 5.
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Skeletal muscle dysfunction is associated with derangements in mitochondrial bioenergetics (but not UCP3) in a rodent model of sepsis.在脓毒症啮齿动物模型中,骨骼肌功能障碍与线粒体生物能量学紊乱(而非解偶联蛋白3)相关。
Am J Physiol Endocrinol Metab. 2015 May 1;308(9):E713-25. doi: 10.1152/ajpendo.00562.2014. Epub 2015 Feb 24.
3
Ameliorated stress related proteins are associated with improved cardiac function by sarcoplasmic reticulum calcium ATPase gene transfer in heart failure.
改善的应激相关蛋白通过肌浆网钙 ATP 酶基因转移与心力衰竭的心脏功能改善相关。
J Geriatr Cardiol. 2012 Sep;9(3):269-77. doi: 10.3724/SP.J.1263.2012.05299.
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Proteome reference map and regulation network of neonatal rat cardiomyocyte.新生儿大鼠心肌细胞蛋白质组参考图谱和调控网络。
Acta Pharmacol Sin. 2011 Sep;32(9):1116-27. doi: 10.1038/aps.2011.86. Epub 2011 Aug 15.
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Proteomics and mass spectrometry: what have we learned about the heart?蛋白质组学与质谱分析:我们对心脏有了哪些了解?
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