Are animal models predictive for human postmortem muscle protein degradation?
Are animal models predictive for human postmortem muscle protein degradation?
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DOI：
10.1007/s00414-017-1643-1
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发表时间：
2017-11
影响因子：
2.1
通讯作者：
Pittner S
中科院分区：
文献类型：
--
作者：
Ehrenfellner B;Zissler A;Steinbacher P;Monticelli FC;Pittner S
死后间隔（PMI）的精确判定是法医案件工作的一个关键方面。尽管目前有多种方法可用，但案件的高度异质性以及相应的死后变化常常限制了许多方法的有效性和充分性。最近，有人提出了一种通过分析肌肉蛋白质死后变化来估计死亡时间的新方法。然而，有必要提高其可靠性和准确性，特别是通过分析蛋白质降解的可能影响因素。理想情况下，这需要在标准化动物模型上进行研究，然而，这需要通过比较人类和动物组织，在这种特定的蛋白质降解图谱的情况下进行验证。只有当蛋白质降解事件在不同物种中以可比的方式发生时，相应的研究结果才能从动物模型充分应用到人类身上。因此，对两种常用动物模型（小鼠和猪）的样本以及具有差异很大的PMI的代表性蛋白质图谱的法医案例进行了分析。尽管物种之间存在生理和物理差异，但蛋白质印迹分析显示，大多数所研究的蛋白质具有相似的模式。甚至大多数降解事件也是以可比的方式发生的。然而，在其他一些方面，人类和动物的图谱存在明显差异。这一系列实验的结果清楚地表明，在考虑使用动物模型时，比较研究非常重要。尽管动物模型可以反映人类蛋白质降解过程的基本原理，但我们也了解到在不同哺乳动物物种中，就蛋白质特异性和方法功能性而言，所开发方法应用的困难和局限性。
A most precise determination of the postmortem interval (PMI) is a crucial aspect in forensic casework. Although there are diverse approaches available to date, the high heterogeneity of cases together with the respective postmortal changes often limit the validity and sufficiency of many methods. Recently, a novel approach for time since death estimation by the analysis of postmortal changes of muscle proteins was proposed. It is however necessary to improve the reliability and accuracy, especially by analysis of possible influencing factors on protein degradation. This is ideally investigated on standardized animal models that, however, require legitimization by a comparison of human and animal tissue, and in this specific case of protein degradation profiles. Only if protein degradation events occur in comparable fashion within different species, respective findings can sufficiently be transferred from the animal model to application in humans. Therefor samples from two frequently used animal models (mouse and pig), as well as forensic cases with representative protein profiles of highly differing PMIs were analyzed. Despite physical and physiological differences between species, western blot analysis revealed similar patterns in most of the investigated proteins. Even most degradation events occurred in comparable fashion. In some other aspects, however, human and animal profiles depicted distinct differences. The results of this experimental series clearly indicate the huge importance of comparative studies, whenever animal models are considered. Although animal models could be shown to reflect the basic principles of protein degradation processes in humans, we also gained insight in the difficulties and limitations of the applicability of the developed methodology in different mammalian species regarding protein specificity and methodic functionality.
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DOI：
10.1186/1747-5341-4-2
发表时间：
2009-01-15
期刊：
Philosophy, ethics, and humanities in medicine : PEHM
影响因子：
--
作者：
Shanks N;Greek R;Greek J
通讯作者：
Greek J
影响因子：
2.2
作者：
Introna, Francesco;De Donno, Antonio;Campobasso, Carlo P.
通讯作者：
Campobasso, Carlo P.
影响因子：
2.2
作者：
MADEA, B
通讯作者：
MADEA, B
影响因子：
2.1
作者：
Poloz, Yekaterina O.;O'Day, Danton H.
通讯作者：
O'Day, Danton H.
影响因子：
2.2
作者：
Henssge, Claus;Madea, Burkhard
通讯作者：
Madea, Burkhard