The Use of Protein Markers for the Estimation of the Postmortem Interval

Chapter
First Online:
Part of the Forensic Pathology Reviews book series (FPR, volume 6)

Abstract

The postmortem interval (PMI) is a critical variable in any death ­investigation. The goal is to elucidate a new and precise biochemical method for PMI determination in humans. Specific protein tissue markers show predictable and precise postmortem degradation patterns that could be utilized to develop a new method for PMI determination. We provide a compilation of available research in this field and review the use of calmodulin-binding proteins as PMI markers. Finally, we propose the development of a portable, hand-held device that will allow the use of protein markers for PMI determination at the scene of a crime.

Keywords

Postmortem interval Protein Degradation Calmodulin Calpain 
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References

  1. 1.
    Arbuzova A, Schmitz AAP, Vergères G (2002) Cross-talk unfolded: MARCKS proteins. Biochem J 362(1):1–12PubMedCrossRefGoogle Scholar
  2. 2.
    Bandman E, Zdanis D (1988) An immunological method to assess protein degradation in post-mortem muscle. Meat Sci 22(1):1–19CrossRefGoogle Scholar
  3. 3.
    Bee G, Anderson AL, Lonergan SM et al (2007) Rate and extent of pH decline affect proteolysis of cytoskeletal proteins and water-holding capacity in pork. Meat Sci 76(2):359–365CrossRefGoogle Scholar
  4. 4.
    Coe JI (1993) Postmortem chemistry update: emphasis on forensic application. Am J Forensic Med Pathol 14:91–117PubMedCrossRefGoogle Scholar
  5. 5.
    Cohen P, Klee CB (1988) Calmodulin. Elsevier, AmsterdamGoogle Scholar
  6. 6.
    Crecelius A, Götz A, Arzberger T et al (2008) Assessing quantitative post-mortem changes in the gray matter of the human frontal cortex proteome by 2-D DIGE. Proteomics 8(6):1276–1291PubMedCrossRefGoogle Scholar
  7. 7.
    Dosemeci A, Reese TS, Petersen J et al (2000) A novel particulate form of Ca2+/CaMKII-dependent protein kinase II in neurons. J Neurosci 20(9):3076–3084PubMedGoogle Scholar
  8. 8.
    Dong Z, Saikumar P, Weinberg JM et al (2006) Calcium in cell injury and death. Annu Rev Pathol 1:405–434PubMedCrossRefGoogle Scholar
  9. 9.
    Dulong S, Goudenege S, Vuillier-Devillers K et al (2004) Myristoylated alanine-rich C kinase substrate (MARCKS) is involved in myoblast fusion through its regulation by protein kinase Cα and calpain proteolytic cleavage. Biochem J 382(3):1015–1023PubMedCrossRefGoogle Scholar
  10. 10.
    Fountoulakis M, Hardmeier R, Höger H et al (2001) Postmortem changes in the level of brain proteins. Exp Neurol 167(1):86–94PubMedCrossRefGoogle Scholar
  11. 11.
    Franzén B, Yang Y, Sunnemark D et al (2003) Dihydropyrimidinase related protein-2 as a biomarker for temperature and time dependent post mortem changes in the mouse brain proteome. Proteomics 3(10):1920–1929PubMedCrossRefGoogle Scholar
  12. 12.
    Fritz JD, Greaser ML (1991) Changes in titin and nebulin in postmortem bovine muscle as revealed by gel electrophoresis, western blotting and immunofluorescence microscopy. J Food Sci 56:607–615CrossRefGoogle Scholar
  13. 13.
    Geesink GH, Koohmaraie M (1999) Effect of calpastatin on degradation of myofibrillar proteins by μ-calpain under postmortem conditions. J Anim Sci 77(10):2685–2692PubMedGoogle Scholar
  14. 14.
    Geesink GH, Kuchay S, Chishti AH (2006) μ-Calpain is essential for postmortem proteolysis of muscle proteins. J Anim Sci 84(10):2834–2840PubMedCrossRefGoogle Scholar
  15. 15.
    Geesink GH, Taylor RG, Koohmaraie M (2005) Calpain 3/p94 is not involved in postmortem proteolysis. J Anim Sci 83(7):1646–1652PubMedGoogle Scholar
  16. 16.
    Goll DE, Thompson VF, Li H et al (2003) The calpain system. Physiol Rev 83(3):731–801PubMedGoogle Scholar
  17. 17.
    Goni-Oliver P, Avila J, Hernandez F (2009) Calpain-mediated cleavage of GSK-3 in post-mortem brain samples. J Neurosci Res 87:1156–1161PubMedCrossRefGoogle Scholar
  18. 18.
    Grange-Midroit M, García-Sevilla JA, Ferrer-Alcón M et al (2002) G protein-coupled receptor kinases, β-arrestin-2 and associated regulatory proteins in the human brain: Postmortem changes, effect of age and subcellular distribution. Mol Brain Res 101(1–2):39–51PubMedCrossRefGoogle Scholar
  19. 19.
    Hajimohammadreza I, Raser KJ, Nath R et al (1997) Neuronal nitric oxide synthase and calmodulin-dependent protein kinase IIα undergo neurotoxin-induced proteolysis. J Neurochem 69(3):1006–1013PubMedCrossRefGoogle Scholar
  20. 20.
    Ho CY, Stromer MH, Robson RM (1994) Identification of the 30 kDa polypeptide in post mortem skeletal muscle as a degradation product of troponin-T. Biochimie 76(5):369–375PubMedCrossRefGoogle Scholar
  21. 21.
    Ho C, Stromer MH, Robson RM (1996) Effect of electrical stimulation on postmortem titin, nebulin, desmin, and troponin-T degradation and ultrastructural changes in bovine longissimus muscle. J Anim Sci 74(7):1563–1575PubMedGoogle Scholar
  22. 22.
    Ho C, Stromer MH, Rouse G et al (1997) Effects of electrical stimulation and postmortem storage on changes in titin, nebulin, desmin, troponin-T, and muscle ultrastructure in bos indicus crossbred cattle. J Anim Sci 75(2):366–376PubMedGoogle Scholar
  23. 23.
    Huff-Lonergan E, Mitsuhashi T, Beekman DD et al (1996a) Proteolysis of specific muscle structural proteins by μ-calpain at low pH and temperature is similar to degradation in postmortem bovine muscle. J Anim Sci 74(5):993–1008PubMedGoogle Scholar
  24. 24.
    Huff-Lonergan E, Mitsuhashi T, Parrish FC Jr et al (1996b) Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting comparisons of purified myofibrils and whole muscle preparations for evaluating titin and nebulin in postmortem bovine muscle. J Anim Sci 74(4):779–785PubMedGoogle Scholar
  25. 25.
    Huff-Lonergan E, Parrish FC Jr, Robson RM (1995) Effects of postmortem aging time, animal age, and sex on degradation of titin and nebulin in bovine longissimus muscle. J Anim Sci 73(4):1064–1073PubMedGoogle Scholar
  26. 26.
    Hunsucker SW, Solomon B, Gawryluk J et al (2008) Assessment of post-mortem-induced changes to the mouse brain proteome. J Neurochem 105(3):725–737PubMedCrossRefGoogle Scholar
  27. 27.
    Hwang IH, Park BY, Kim JH et al (2005) Assessment of postmortem proteolysis by gel-based proteome analysis and its relationship to meat quality traits in pig longissimus. Meat Sci 69(1):79–91CrossRefGoogle Scholar
  28. 28.
    Ilian MA, Bekhit AE, Bickerstaffe R (2004) The relationship between meat tenderization, myofibril fragmentation and autolysis of calpain 3 during post-mortem aging. Meat Sci 66(2):387–397CrossRefGoogle Scholar
  29. 29.
    Irving EA, Nicoll J, Graham DI et al (1996) Increased tau immunoreactivity in oligodendrocytes following human stroke and head injury. Neurosci Lett 213(3):189–192PubMedGoogle Scholar
  30. 30.
    Jia X, Ekman M, Grove H, Færgestad EM et al (2007) Proteome changes in bovine longissimus thoracis muscle during the early postmortem storage period. J Proteome Res 6(7):2720–2731PubMedCrossRefGoogle Scholar
  31. 31.
    Jia X, Hildrum KI, Westad F et al (2006a) Changes in enzymes associated with energy metabolism during the early post mortem period in longissimus thoracis bovine muscle analyzed by proteomics. J Proteome Res 5(7):1763–1769PubMedCrossRefGoogle Scholar
  32. 32.
    Jia X, Hollung K, Therkildsen M et al (2006b) Proteome analysis of early post-mortem changes in two bovine muscle types: M. longissimus dorsi and M. semitendinosis. Proteomics 6(3):936–944PubMedCrossRefGoogle Scholar
  33. 33.
    Johnson GVW, Greenwood JA, Costello AC et al (1991) The regulatory role of calmodulin in the proteolysis of individual neurofilament proteins by calpain. Neurochem Res 16(8):869–873PubMedCrossRefGoogle Scholar
  34. 34.
    Jones RJ, Jourd’heuil D, Salerno JC et al (2007) iNOS regulation by calcium/calmodulin-dependent protein kinase II in vascular smooth muscle. Am J Physiol Heart Circ Physiol 292(6):2634–2642CrossRefGoogle Scholar
  35. 35.
    Kang S, Kassam N, Gauthier ML et al (2003) Post-mortem changes in calmodulin binding proteins in muscle and lung. Forensic Sci Int 131(2–3):140–147PubMedCrossRefGoogle Scholar
  36. 36.
    Koohmaraie M, Geesink GH (2006) Contribution of postmortem muscle biochemistry to the delivery of consistent meat quality with particular focus on the calpain system. Meat Sci 74(1):34–43CrossRefGoogle Scholar
  37. 37.
    Kuai J, Liu Y, Zhang Y (2008) A study on the relationship between the degradation of tubulin in cardiac muscle and lung of rat and the postmortem interval. Chin J Forensic Med 23(2):96–98Google Scholar
  38. 38.
    Lametsch R, Karlsson A, Rosenvold K et al (2003) Postmortem proteome changes of porcine muscle related to tenderness. J Agric Food Chem 51(24):6992–6997PubMedCrossRefGoogle Scholar
  39. 39.
    Larsen K, Lygren B, Sjaastad I et al (2008) Diastolic dysfunction in alveolar hypoxia: A role for interleukin-18- mediated increase in protein phosphatase 2A. Cardiovasc Res 80(1):47–54PubMedCrossRefGoogle Scholar
  40. 40.
    Li J, Gould TD, Yuan P et al (2003) Post-mortem interval effects on the phosphorylation of signaling proteins. Neuropsychopharmacology 28(6):1017–1025PubMedCrossRefGoogle Scholar
  41. 41.
    Li X, Greenwood AF, Powers R et al (1996) Effects of postmortem interval, age, and alzheimer’s disease on G-proteins in human brain. Neurobiol Aging 17(1):115–122PubMedCrossRefGoogle Scholar
  42. 42.
    Liu F, Iqbal-Grundke I, Iqbal K et al (2005a) Truncation and activation of calcineurin A by calpain I in alzheimer disease brain. J Biol Chem 280(45):37755–37762PubMedCrossRefGoogle Scholar
  43. 43.
    Liu L, Cheng J, Wang F (2005b) An experimental study on relationship between degradation of thyroglobulin and postmortem interval by immunohistochemistry. Chin J Forensic Med 20(5):265–267Google Scholar
  44. 44.
    Liu Y, Kuai J-X, Zhang Y-W et al (2008a) The relationship between the degradation of actin and the postmortem interval in rats. J Forensic Med 24(3):165–167Google Scholar
  45. 45.
    Liu Y, Kuai J-X, Zhang Y-W (2008b) A study on the content changes of tubulin in liver, spleen and kidney of rats killed by bleeding. Chin J Forensic Med 23(5):315–317Google Scholar
  46. 46.
    MacDonnell SM, Weisser-Thomas J, Kubo H et al (2009) CaMKII negatively regulates calcineurin-NFAT signaling in cardiac myocytes. Circ Res 105(4):316–325PubMedCrossRefGoogle Scholar
  47. 47.
    Melody JL, Lonergan SM, Rowe LJ et al (2003) Early postmortem biochemical factors influence tenderness and water-holding capacity of three porcine muscles. J Anim Sci 82(4):1195–1205Google Scholar
  48. 48.
    Morioka M, Hamada J, Ushio Y et al (1999) Potential role of calcineurin for brain ischemia and traumatic injury. Prog Neurobiol 58(1):1–30PubMedCrossRefGoogle Scholar
  49. 49.
    Morzel M, Terlouw C, Chambon C et al (2008) Muscle proteome and meat eating qualities of longissimus thoracis of “blonde d’aquitaine” young bulls: A central role of HSP27 isoforms. Meat Sci 78(3):297–304CrossRefGoogle Scholar
  50. 50.
    Obasanjo-Blackshire K, Mesquita R, Jabr RI et al (2006) Calcineurin regulates NFAT-dependent iNOS expression and protection of cardiomyocytes: Co-operation with src tyrosine kinase. Cardiovasc Res 71(4):672–683PubMedCrossRefGoogle Scholar
  51. 51.
    Park BY, Kim NK, Lee CS et al (2007) Effect of fiber type on postmortem proteolysis in longissimus muscle of landrace and korean native black pigs. Meat Sci 77(4):482–491CrossRefGoogle Scholar
  52. 52.
    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 Leg Med 123(4):305–314CrossRefGoogle Scholar
  53. 53.
    Rhee MS, Ryu YC, Imm JY et al (2000) Combination of low voltage electrical stimulation and early postmortem temperature conditioning on degradation of myofibrillar proteins in korean native cattle (hanwoo). Meat Sci 55(4):391–396CrossRefGoogle Scholar
  54. 54.
    Rowe LJ, Maddock KR, Lonergan SM et al (2004) Oxidative environments decrease tenderization of beef steaks through inactivation of μ-calpain. J Anim Sci 82(11):3254–3266PubMedGoogle Scholar
  55. 55.
    Sabucedo AJ, Furton KG (2003) Estimation of postmortem interval using the protein marker cardiac troponin I. Forensic Sci Int 134(1):11–16PubMedCrossRefGoogle Scholar
  56. 56.
    Sanoudou D, Kang PB, Haslett JN et al (2004) Transcriptional profile of postmortem skeletal muscle. Physiol Genomics 16:222–228PubMedGoogle Scholar
  57. 57.
    Schwab C, Bondada V, Sparks DL et al (1994) Postmortem changes in the levels and localization of microtubule-associated proteins (tau, MAP2 and MAP1B) in the rat and human hippocampus. Hippocampus 4(2):210–225PubMedCrossRefGoogle Scholar
  58. 58.
    Seki K, Chen H, Huang K (1995) Dephosphorylation of protein kinase C substrates, neurogranin, neuromodulin, and MARCKS, by calcineurin and protein phosphatases 1 and 2A. Arch Biochem Biophys 316(2):673–679PubMedCrossRefGoogle Scholar
  59. 59.
    Shi Y (2009) Serine/threonine phosphatases: mechanism through structure. Cell 139(3):468–484PubMedCrossRefGoogle Scholar
  60. 60.
    Shibasaki F, McKeon F (1995) Calcineurin functions in Ca2+−activated cell death in mammalian cells. J Cell Biol 131(3):735–473PubMedCrossRefGoogle Scholar
  61. 61.
    Shioda N, Moriguchi S, Shirasaki Y et al (2006) Generation of constitutively active calcineurin by calpain contributes to delayed neuronal death following mouse brain ischemia. J Neurochem 98(1):310–320PubMedCrossRefGoogle Scholar
  62. 62.
    Skelding KA, Rostas JAP (2009) Regulation of CaMKII in vivo: the importance of targeting and the intracellular microenvironment. Neurochem Res 34(10):1792–1804PubMedCrossRefGoogle Scholar
  63. 63.
    Sorimachi Y, Harada K, Yoshida K (1996) Involvement of calpain in postmortem proteolysis in the rat brain. Forensic Sci Int 81(2–3):165–174PubMedCrossRefGoogle Scholar
  64. 64.
    Sturner WQ (1963) The vitreous humour: postmortem potassium changes. Lancet 1:807–808PubMedCrossRefGoogle Scholar
  65. 65.
    Tao-Cheng J, Gallant PE, Brightman MW et al (2007) Structural changes at synapses after delayed perfusion fixation in different regions of the mouse brain. J Comp Neurol 501(5):731–740PubMedCrossRefGoogle Scholar
  66. 66.
    Tao-Cheng J, Vinade L, Smith C et al (2001) Sustained elevation of calcium induces Ca2+/calmodulin-dependent protein kinase II clusters in hippocampal neurons. Neuroscience 106(1):69–78PubMedCrossRefGoogle Scholar
  67. 67.
    Tavichakorntrakool R, Prasongwattana V, Sriboonlue P et al (2008) Serial analyses of postmortem changes in human skeletal muscle: a case study of alterations in proteome profile, histology, electrolyte contents, water composition, and enzyme activity. Proteomics Clin Appl 2(9):1255–1264CrossRefGoogle Scholar
  68. 68.
    Taylor RG, Geesink GH, Thompson VF et al (1995) Is Z-disk degradation responsible for postmortem tenderization? J Anim Sci 73(5):1351–1367PubMedGoogle Scholar
  69. 69.
    Thaik-Oo M, Tanaka E, Tsuchiya T et al (2002) Estimation of postmortem interval from hypoxic inducible levels of vascular endothelial growth factor. J Forensic Sci 47(1):186–189PubMedGoogle Scholar
  70. 70.
    Thelen M, Rosen A, Nairn AC et al (1991) Regulation by phosphorylation of reversible association of a myristoylated protein kinase C substrate with the plasma membrane. Nature 351(6324):320–322PubMedCrossRefGoogle Scholar
  71. 71.
    Van Zwieten EJ, Ravid R, Van Der Sluis PJ et al (1991) Increased vasopressin immunoreactivity in the rat brain after a postmortem interval of 6 hours. Brain Res 550(2):263–267PubMedCrossRefGoogle Scholar
  72. 72.
    Vass AA, Barshick S, Sega G et al (2002) Decomposition chemistry of human remains: a new methodology for determining the postmortem interval. J Forensic Sci 47(3):542–553PubMedGoogle Scholar
  73. 73.
    Veiseth E, Shackelford SD, Wheeler TL et al (2004) Indicators of tenderization are detectable by 12 h postmortem in ovine longissimus. J Anim Sci 82(5):1428–1436PubMedGoogle Scholar
  74. 74.
    Verkhratsky A (2007) Calcium and cell death. Subcell Biochem 45:465–480PubMedCrossRefGoogle Scholar
  75. 75.
    Vila-Petroff M, Salas MA, Said M et al (2007) CaMKII inhibition protects against necrosis and apoptosis in irreversible ischemia-reperfusion injury. Cardiovasc Res 73(4):689–698PubMedCrossRefGoogle Scholar
  76. 76.
    Walker G, Pfeilschifter J, Otten U et al (2001) Proteolytic cleavage of inducible nitric oxide synthase (iNOS) by calpain I. Biochim Biophys Acta Gen Subj 1568(3):216–224CrossRefGoogle Scholar
  77. 77.
    Wehner F, Steinriede A, Martin D (2006) Two-tailed delimitation of the time of death by immunohistochemical detection of somatostatin and GFAP. Forensic Sci Med Pathol 2(4):241–248CrossRefGoogle Scholar
  78. 78.
    Wehner F, Wehner H, Schieffer MC et al (2000) Delimitation of the time of death by immunohistochemical detection of thyroglobulin. Forensic Sci Int 110(3):199–206PubMedCrossRefGoogle Scholar
  79. 79.
    Wehner F, Wehner H, Schieffer MC et al (1999) Delimitation of the time of death by immunohistochemical detection of insulin in pancreatic β-cells. Forensic Sci Int 105(3):161–169PubMedCrossRefGoogle Scholar
  80. 80.
    Wehner F, Wehner H, Subke J (2001a) Delimitation of the time of death by immunohistochemical detection of glucagon in pancreatic α-cells. Forensic Sci Int 124(2–3):192–199PubMedCrossRefGoogle Scholar
  81. 81.
    Wehner F, Wehner H, Subke J (2001b) Delimitation of the time of death by immunohistochemical detection of calcitonin. Forensic Sci Int 122(2–3):89–94PubMedCrossRefGoogle Scholar
  82. 82.
    Wu H, Tomizawa K, Oda Y et al (2004) Critical role of calpain-mediated cleavage of calcineurin in excitotoxic neurodegeneration. J Biol Chem 279(6):4929–4940PubMedCrossRefGoogle Scholar
  83. 83.
    Xiao JH, Chen YC (2005) A study on the relationship between the degradation of protein and the postmortem interval. Fa Yi Xue Za Zhi 21(2):110–112PubMedGoogle Scholar
  84. 84.
    Zheng X, Zhang Y, Zhi X (2006) Estimation of postmortem interval by determination of troponin I using western blot technique in human pectoralis major. Chin J Forensic Med 21(3):146–148Google Scholar
  85. 85.
    Zhou L, Zhu D (2009) Neuronal nitric oxide synthase: Structure, subcellular localization, regulation, and clinical implications. Nitric Oxide Biol Chem 20(4):223–230CrossRefGoogle Scholar
  86. 86.
    Zolk O, Schenke C, Sarikas A (2006) The ubiquitin-proteasome system: focus on the heart. Cardiovasc Res 70(3):410–421PubMedCrossRefGoogle Scholar
  87. 87.
    Espeel M, Hashimoto T, De Craemer D, Roels F (1990) Immunocytochemical detection of peroxisomal beta-oxidation enzymes in cryostat and paraffin sections of human post mortem liver. Histochem J 22(1):57–62PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Cell and Systems BiologyUniversity of TorontoTorontoCanada
  2. 2.Department of BiologyUniversity of TorontoMississaugaCanada

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