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01-05-2021 | Original Article

PP2A-C may be a promising candidate for postmortem interval estimation

Authors: Jing Wang, Gang Chen, Hongyan Qian, Qing Shang, Jing Xiao, Min Liang, Baoyao Gao, Tao Li, Xinshe Liu

Published in: International Journal of Legal Medicine | Issue 3/2021

Abstract

Determining the postmortem interval (PMI) is an important task in forensic pathology. However, a reliable means of determining the PMI between 24 h and approximately 7 days after death has not yet been established. A previous study demonstrated that subunit A of protein phosphatase 2A (PP2A-A) is a promising candidate to estimate the PMI during the first 96 h. However, more detailed work is still needed to investigate PP2A’s function in PMI estimation. PP2A is a serine/threonine phosphatase consisting of three subunits (PP2A-A, PP2A-B, and PP2A-C), and its activation is reflected by Tyr-307 phosphorylation of the catalytic subunit (P-PP2A-C). In this study, we speculated that the other two subunits of PP2A and the activation of PP2A may play different roles in estimating the PMI. For this purpose, mice were euthanized and stored at different temperatures (4, 15, and 25 °C). At each temperature, the musculus vastus lateralis was collected at different time points (0, 24, 48, and 96 h) to investigate the degradation of PP2A-B, PP2A-C, and P-PP2A-C (Tyr-307). Homocysteine (Hcy) was used to establish a hyperhomocysteinemia animal model to explore the effects of plasma Hcy on PMI estimation. The data showed not only that PP2A-C was more stable than PP2A-B, but also that it was not affected by homocysteine (Hcy). These characteristics make PP2A-C a promising candidate for short-term (24 h to 48 h) PMI estimation.

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Crostack C, Sehner S, Raupach T, Anders S (2017) Re-establishment of rigor mortis: evidence for a considerably longer post-mortem time span. Int J Legal Med 131:1039–1042CrossRef

Henssge C, Althaus L, Bolt J, Freislederer A, Haffner HT, Henssge CA, Hoppe B, Schneider V (2000) Experiences with a compound method for estimating the time since death. Int J Legal Med 113:303–319CrossRef

M. B (2005) Is there recent progress in the estimation of the postmortem interval by means of thanatochemistry? Forensic Sci Int 151:139–149CrossRef

Lv Y-H, Ma J-L, Pan H, Zhang H, Li W-C, Xue A-M, Wang H-J, Ma K-J, Chen L (2016) RNA degradation as described by a mathematical model for postmortem interval determination. J Forensic Legal Med 44:43–52

Oehmichen M (1980) Enzyme alterations in brain tissue during the early postmortal interval with reference to the histomorphology: review of the literature. Z Rechtsmed 85:81–95CrossRef

Pittner S, Ehrenfellner B, Zissler A, Racher V, Trutschnig W, Bathke AC, Sänger AM, Stoiber W, Steinbacher P, Monticelli FC (2017) First application of a protein-based approach for time since death estimation. Int J Legal Med 131:479–483CrossRef

Zissler A, Ehrenfellner B, Foditsch EE, Monticelli FC, Pittner S (2018) Does altered protein metabolism interfere with postmortem degradation analysis for PMI estimation? Int J Legal Med 132:1349–1356CrossRef

Henssge C, Althaus L, Bolt J, Freislederer A, Haffner HT, Henssge CA, Hoppe B, Schneider V (2000) Experiences with a compound method for estimating the time since death. II. Integration of non-temperature-based methods. Int J Legal Med 113:320–331CrossRef

Brooks JW (2016) Postmortem changes in animal carcasses and estimation of the postmortem interval. Vet Pathol 53:929–940CrossRef

10.

Kumar S, Ali W, Singh US, Kumar A, Bhattacharya S, Verma AK (2015) The effect of elapsed time on the cardiac troponin-T (cTnT) proteolysis in case of death due to burn: a study to evaluate the potential forensic use of cTnT to determine the postmortem interval. Sci Justice 55:189–194CrossRef

11.

Kumar S, Ali W, Singh US, Kumar A, Bhattacharya S, Verma AK, Rupani R (2016) Temperature-dependent postmortem changes in human cardiac troponin-T (cTnT): An approach in estimation of time since death. J Forensic Sci 61:S241–S245CrossRef

12.

Lee D-G, Yang KE, Hwang JW, Kang H-S, Lee S-Y, Choi S, Shin J, Jang I-S, An HJ, Chung H, Jung H-I, Choi J-S (2016) Degradation of kidney and psoas muscle proteins as indicators of post-mortem interval in a rat model, with use of lateral flow technology. PLoS One 11:e0160557CrossRef

13.

Ansari KA, Rand A, Hendrickson H, Bentley MD (1976) Qualitative and quantitative studies on human myelin basic protein in situ with respect to time interval between death and autopsy. J Neuropathol Exp Neurol 35:180–190CrossRef

14.

Ross B, Dawson D, Dewar D, Macrae M, Knowler J, McCulloch J (1993) Effects of post-mortem delay on high affinity forskolin binding sites and adenylate cyclase activity in rat and human striatum and cerebral cortex. Brain Res 629(2):225–230

15.

Goggins M, Scott JM, Weir DG (1998) Regional differences in protein Carboxymethylation in post-mortem human brain. Clin Sci 94:677–685CrossRef

16.

Procopio N, Williams A, Chamberlain AT, Buckley M (2018) Forensic proteomics for the evaluation of the post-mortem decay in bones. J Proteomics 177:21–30

17.

Bolton SN, Whitehead MP, Dudhia J, Baldwin TC, Sutton R (2015) Investigating the postmortem molecular biology of cartilage and its potential forensic applications. J Forensic Sci 60:1061–1067CrossRef

18.

Vass AA, Barshick SA, Sega G, Caton J, Synstelien JA (2002) Decomposition chemistry of human remains: a new methodology for determining the postmortem interval. J Forensic Sci 47:542–553CrossRef

19.

Pittner S, Monticelli FC, Pfisterer A, Zissler A, Sanger A (2016) Postmortem degradation of skeletal muscle proteins: a novel approach to determine the time since death. Int J Legal Med 130(2):421–431

20.

Tomita Y, Nihira M, Ohno Y, Sato S (2004) Ultrastructural changes during in situ early postmortem autolysis in kidney, pancreas, liver, heart and skeletal muscle of rats. Legal Med 6:25–31CrossRef

21.

Ehrenfellner B, Zissler A, Steinbacher P, Monticelli FC, Pittner S (2017) Are animal models predictive for human postmortem muscle protein degradation? Int J Legal Med 131:1615–1621CrossRef

22.

Choi K-M, Zissler A, Kim E, Ehrenfellner B, Cho E, Lee S-i, Steinbacher P, Yun KN, Shin JH, Kim JY, Stoiber W, Chung H, Monticelli FC, Kim J-Y, Pittner S (2019) Postmortem proteomics to discover biomarkers for forensic PMI estimation. Int J Legal Med 133:899–908CrossRef

23.

He W, Yan X, Pan S (2018) Amphetamine neurotoxicity in PC12 cells through the PP2A/AKT/GSK3beta pathway. Neurotox Res 34:233–240CrossRef

24.

Janssens V, Goris J (2001) Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J 353:417–439CrossRef

25.

Creighton MT, Kolton A, Kataya ARA, Maple-Grodem J, Averkina IO, Heidari B, Lillo C (2017) Methylation of protein phosphatase 2A — influence of regulators and environmental stress factors. Plant Cell Environ 40:2347–2358CrossRef

26.

Zhang C, Tian Q, Wei W, Peng JH, Liu GP, Zhou XW, Wang Q, Wang DW, Wang JZ (2008) Homocysteine induces tau phosphorylation by inactivating protein phosphatase 2A in rat hippocampus. Neurobiol Aging 29:1654–1665CrossRef

27.

Sangodkar J, Farrington CC, McClinch K, Galsky MD, Kastrinsky DB, Narla G (2016) All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase. FEBS J 283:1004–1024CrossRef

28.

Chen G, Li T, Xiao J, Wang J, Shang Q, Qian H, Qiao C, Zhang P, Chen T, Liu X (2020) Ifenprodil attenuates methamphetamine-induced behavioral sensitization through the GluN2B-PP2A-AKT Cascade in the dorsal striatum of mice. Neurochem Res 45:891–901CrossRef

29.

Poloz YO, O’Day DH (2009) Determining time of death: temperature-dependent postmortem changes in calcineurin a, MARCKS, CaMKII, and protein phosphatase 2A in mouse. Int J Legal Med 123:305–314CrossRef

30.

Skovierova H, Vidomanova E, Mahmood S, Sopkova J, Drgova A, Cervenova T, Halasova E, Lehotsky J (2016) The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int J Mol Sci 17(10):1733

31.

Pittner S, Ehrenfellner B, Monticelli FC, Zissler A, Sänger AM, Stoiber W, Steinbacher P (2016) Postmortem muscle protein degradation in humans as a tool for PMI delimitation. Int J Legal Med 130:1547–1555CrossRef

32.

Slupe AM, Merrill RA, Strack S (2011) Determinants for substrate specificity of protein phosphatase 2A. Enzyme Res 2011:398751CrossRef

33.

LeNoue-Newton M, Watkins GR, Zou P, Germane KL, McCorvey LR, Wadzinski BE, Spiller BW (2011) The E3 ubiquitin ligase- and protein phosphatase 2A (PP2A)-binding domains of the Alpha4 protein are both required for Alpha4 to inhibit PP2A degradation. J Biol Chem 286:17665–17671CrossRef

34.

Wang Y, Zhang Y, Hu W, Xie S, Gong CX, Iqbal K, Liu F (2015) Rapid alteration of protein phosphorylation during postmortem: implication in the study of protein phosphorylation. Sci Rep 5:15709CrossRef

35.

Zhang C-x, Wang Z-y, Li Z, Du M-t, Zhang D-q (2016) Effect of salting temperature on the protein phosphorylation of mutton. Modern Food Sci Technol 32:215–221

36.

Rabaneda LG, Geribaldi-Doldán N, Murillo-Carretero M, Carrasco M, Martínez-Salas JM, Verástegui C, Castro C (2016) Altered regulation of the Spry2/Dyrk1A/PP2A triad by homocysteine impairs neural progenitor cell proliferation. Biochimica et Biophysica Acta (BBA) – Mole Cell Res 1863(12):3015–3026

37.

Chai GS, Jiang X, Ni ZF, Ma ZW, Xie AJ, Cheng XS, Wang Q, Wang JZ, Liu GP (2013) Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine. J Neurochem 124:388–396CrossRef

38.

Guo J, Xu C, Ni S, Zhang S, Li Q, Zeng P, Pi G, Liu E, Sun D-S, Liu Y (2019) Elevation of pS262-tau and demethylated PP2A in retina occurs earlier than in hippocampus during hyperhomocysteinemia. J Alzheimers Dis 68(1):367–381

39.

Chu D, Tan J, Xie S, Jin N, Yin X, Gong CX, Iqbal K, Liu F (2016) GSK-3beta is dephosphorylated by PP2A in a Leu309 methylation-independent manner. J Alzheimers Dis 49:365–375CrossRef

40.

Wang R, Reddy PH (2017) Role of glutamate and NMDA receptors in Alzheimer’s disease. J Alzheimers Dis 57:1041–1048CrossRef

41.

Bryant JC, Westphal RS, BE W (1999) Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Balpha subunit. Biochem J 339:241–246CrossRef

42.

Kang S, Kassam N, Gauthier ML, O’Day DH (2003) Post-mortem changes in calmodulin binding proteins in muscle and lung. Forensic Sci Int 131:140–147CrossRef

Title: PP2A-C may be a promising candidate for postmortem interval estimation
Authors: Jing Wang
Gang Chen
Hongyan Qian
Qing Shang
Jing Xiao
Min Liang
Baoyao Gao
Tao Li
Xinshe Liu
Publication date: 01-05-2021
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Legal Medicine / Issue 3/2021
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-020-02466-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

PP2A-C may be a promising candidate for postmortem interval estimation

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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