Early Ischaemic Preconditioning of Spinal Cord Enhanced the Binding Profile of Heat Shock Protein 70 with Neurofilaments and Promoted its Nuclear Translocation after Thoraco-abdominal Aortic Occlusion in Pigs
Early Ischaemic Preconditioning of Spinal Cord Enhanced the Binding Profile of Heat Shock Protein 70 with Neurofilaments and Promoted its Nuclear Translocation after Thoraco-abdominal Aortic Occlusion in Pigs
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DOI：
10.1016/j.ejvs.2011.12.028
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发表时间：
2012-04-01
影响因子：
5.7
通讯作者：
Matsagkas, M. I.
中科院分区：
文献类型：
--
作者：
Kyrou, I. E.;Papakostas, J. C.;Matsagkas, M. I.
目的：热休克蛋白70 （Hsp70）在正常神经元中被大量检测到，这种基础含量可以保护细胞免受有害条件的侵害，而不需要额外的合成。在此，我们在早期缺血预处理（IPC）实验模型中研究了这些基础水平的Hsp70的潜在保护作用，表明该蛋白可能作为第一个保护窗口的作用。设计、材料和方法：42头猪建立胸腹主动脉阻塞模型。采用两组12只动物进行神经学评价。其余5组30只进行免疫沉淀和免疫组织化学研究。这些实验分别研究了Hsp70/细胞骨架元件的结合关系和Hsp70的细胞分布。结果：IPC缺血组神经功能评分明显高于缺血组，提示IPC具有保护作用（P = 0.003）。免疫沉淀显示，早期IPC显著增加了Hsp70/神经丝的结合谱（P = 0.025）。此外，观察到Hsp70易位到细胞核中，这种易位一直保持到持续缺血。结论：这些结果表明，Hsp70可能在脊髓早期损伤中发挥重要作用，在损伤开始时保护神经丝，确保细胞核的功能和完整性。(C) 2012年欧洲血管外科学会。Elsevier Ltd.出版。版权所有。
Objective(s): Heat shock protein 70 (Hsp70) is detected in substantial amounts in normal neurons and this basal content may protect a cell against harmful conditions without the need for additional synthesis. Herein, we investigate the potential protective role of these basal levels of Hsp70, in an early ischaemic preconditioning (IPC) experimental model, suggesting a possible role of this protein as a first window of protection.Design, material and methods: Forty-two pigs were used in an experimental thoraco-abdominal aortic occlusion model. Twelve animals (two groups) were used for neurological evaluation. The remaining 30 animals (five groups) were used for immunoprecipitation and immunohistochemical studies. These were performed to study the binding relationship of Hsp70/cytoskeleton elements and the cellular distribution of Hsp70, respectively.Results: The IPC ischaemia-group showed significant better neurologic scores compared with those of the ischaemia group, indicating a protective role for IPC (P = 0.003). The immunoprecipitations demonstrated that early IPC increased significantly the binding profile of Hsp70/neurofilaments (P = 0.025). In addition, translocation of Hsp70 into the nucleus was observed, which was conserved until the sustained ischaemia.Conclusions: These results indicate that Hsp70 may have an important role in early IPC of the spinal cord, by protecting neurofilaments and by ensuring the functionality and the integrity of the nucleus, at the time the intensive insult begins. (C) 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.