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基于质谱的硒蛋白鉴定和分析:评估鲸模型中心肌病进展的工具。

Selenium protein identification and profiling by mass spectrometry: A tool to assess progression of cardiomyopathy in a whale model.

机构信息

Chemical Sciences Division, National Institute of Standards and Technology, Hollings Marine Laboratory, 331 Fort Johnson Road, Charleston, SC 29412, USA.

Georgia Aquarium, 225 Baker Street NW, Atlanta, GA 30313, USA.

出版信息

J Trace Elem Med Biol. 2017 Dec;44:40-49. doi: 10.1016/j.jtemb.2017.05.005. Epub 2017 Jun 6.

Abstract

Non-ischemic cardiomyopathy is a leading cause of congestive heart failure and sudden cardiac death in humans and in some cases the etiology of cardiomyopathy can include the downstream effects of an essential element deficiency. Of all mammal species, pygmy sperm whales (Kogia breviceps) present the greatest known prevalence of cardiomyopathy with more than half of examined individuals indicating the presence of cardiomyopathy from gross and histo-pathology. Several factors such as genetics, infectious agents, contaminants, biotoxins, and inappropriate dietary intake (vitamins, selenium, mercury, and pro-oxidants), may contribute to the development of idiopathic cardiomyopathy in K. breviceps. Due to the important role Se can play in antioxidant biochemistry and protein formation, Se protein presence and relative abundance were explored in cardiomyopathy related cases. Selenium proteins were separated and detected by multi-dimension liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS), Se protein identification was performed by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS), and Se protein profiles were examined in liver (n=30) and heart tissue (n=5) by SEC/UV/ICP-MS detection. Data collected on selenium proteins was evaluated in the context of individual animal trace element concentration, life history, and histological information. Selenium containing protein peak profiles varied in presence and intensity between animals with no pathological findings of cardiomyopathy and animals exhibiting evidence of cardiomyopathy. In particular, one class of proteins, metallothioneins, was found to be associated with Se and was in greater abundance in animals with cardiomyopathy than those with no pathological findings. Profiling Se species with SEC/ICP-MS proved to be a useful tool to identify Se protein pattern differences between heart disease stages in K. breviceps and an approach similar to this may be applied to other species to study Se protein associations with cardiomyopathy.

摘要

非缺血性心肌病是人类充血性心力衰竭和心源性猝死的主要原因,在某些情况下,心肌病的病因可能包括必需元素缺乏的下游影响。在所有哺乳动物物种中,侏抹香鲸(Kogia breviceps)表现出最高的心肌病患病率,超过一半的受检个体通过大体和组织病理学检查显示存在心肌病。遗传因素、感染因子、污染物、生物毒素和不当的饮食摄入(维生素、硒、汞和促氧化剂)等多种因素可能导致 K. breviceps 特发性心肌病的发生。由于硒在抗氧化生物化学和蛋白质形成中可以发挥重要作用,因此研究了心肌病相关病例中硒蛋白的存在和相对丰度。通过多维液相色谱电感耦合等离子体质谱(LC-ICP-MS)分离和检测硒蛋白,通过液相色谱电喷雾串联质谱(LC-ESI-MS/MS)进行硒蛋白鉴定,通过 SEC/UV/ICP-MS 检测在肝脏(n=30)和心脏组织(n=5)中检查硒蛋白谱。根据个体动物微量元素浓度、生活史和组织学信息评估收集到的硒蛋白数据。在没有心肌病病理发现的动物和表现出心肌病证据的动物之间,含硒蛋白的峰谱在存在和强度上存在差异。特别是,一类蛋白质,金属硫蛋白,与硒有关,并且在患有心肌病的动物中比在没有病理发现的动物中更为丰富。使用 SEC/ICP-MS 对硒物种进行分析是一种有用的工具,可以确定 K. breviceps 中心脏病不同阶段的硒蛋白模式差异,并且类似的方法可以应用于其他物种,以研究硒蛋白与心肌病的关系。

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