Postmortem proteomics to discover biomarkers for forensic PMI estimation.

International journal of legal medicine 2019 May

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The assessment of postmortem degradation of skeletal muscle proteins has emerged as a novel approach to estimate the time since death in the early to mid-postmortem phase (approximately 24 h postmortem (hpm) to 120 hpm). Current protein-based methods are limited to a small number of skeletal muscle proteins, shown to undergo proteolysis after death. In this study, we investigated the usability of a target-based and unbiased system-wide protein analysis to gain further insights into systemic postmortem protein alterations and to identify additional markers for postmortem interval (PMI) delimitation. We performed proteomic profiling to globally analyze postmortem alterations of the rat and mouse skeletal muscle proteome at defined time points (0, 24, 48, 72, and 96 hpm), harnessing a mass spectrometry-based quantitative proteomics approach. Hierarchical clustering analysis for a total of 579 (rat) and 896 (mouse) quantified proteins revealed differentially expressed proteins during the investigated postmortem period. We further focused on two selected proteins (eEF1A2 and GAPDH), which were shown to consistently degrade postmortem in both rat and mouse, suggesting conserved intra- and interspecies degradation behavior, and thus preserved association with the PMI and possible transferability to humans. In turn, we validated the usefulness of these new markers by classical Western blot experiments in a rat model and in human autopsy cases. Our results demonstrate the feasibility of mass spectrometry-based analysis to discover novel protein markers for PMI estimation and show that the proteins eEF1A2 and GAPDH appear to be valuable markers for PMI estimation in humans.

Citation

Kyoung-Min Choi, Angela Zissler, Eunjung Kim, Bianca Ehrenfellner, Eunji Cho, Se-In Lee, Peter Steinbacher, Ki Na Yun, Jong Hwan Shin, Jin Young Kim, Walter Stoiber, Heesun Chung, Fabio Carlo Monticelli, Jae-Young Kim, Stefan Pittner. Postmortem proteomics to discover biomarkers for forensic PMI estimation. International journal of legal medicine. 2019 May;133(3):899-908