Skip to main content

Advertisement

Log in

Estimates of exposure to cold before death from immunohistochemical expression patterns of HSP70 in glomerular podocytes

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

Environmental factors such as outside temperature at the time of death are very important for forensic diagnoses and police investigations. In particular, death in a cold environment is associated with factors of forensic interest, including hypothermia, drowning in cold water, or postmortem body movement by a suspect. Hypothermia raises a special problem because of the difficulty of evaluation during autopsy. We describe here a unique method of estimating antemortem environmental temperature, involving the immunohistochemical analysis of HSP70 expression patterns in glomerular podocytes. Using this method, we found that HSP70 was present in glomerular podocytes at autopsy and that HSP70 was highly expressed, mainly in the nucleus of podocytes, in deaths associated with exposure to cold. Interestingly, this expression pattern was specific to death in a cold environment, including hypothermia and drowning in cold water. Analysis of the pattern of HSP70 expression in glomeruli may therefore be very useful in forensic diagnosis, for determining whether the antemortem environmental temperature was low. Moreover, immunohistochemical and real-time PCR assays of the molecular mechanism of HSP70 and HSF1 expression in glomeruli following exposure to cold indicated that HSP70 was rapidly translocated to the nucleus of podocytes following exposure to cold, but without new protein synthesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Turk EE (2010) Hypothermia. Forensic Sci Med Pathol 6:106–115

    Article  PubMed  Google Scholar 

  2. Wischnewski S (1895) A new feature of death due to hypothermia [in German]. Bote Gericht Med 3:12–20

    Google Scholar 

  3. Hirvonen J (1976) Necropsy findings in fatal hypothermia cases. Forensic Sci 8(2):155–164

    Article  CAS  PubMed  Google Scholar 

  4. Kinzinger R, Risse M, Püschel K (1991) Irrational behavior in exposure to cold. Paradoxical undressing in hypothermia [in German]. Arch Kriminol 187(2):47–56

    CAS  PubMed  Google Scholar 

  5. Rothschild MA, Schneider (1995) “Terminal burrowing behavior”—a phenomenon of lethal hypothermia. Int J Leg Med 107:250–256

    Article  CAS  Google Scholar 

  6. Duguid H, Simpson RG, Stowers JM (1961) Accidental hypothermia. Lancet 278:1213–1219

    Article  Google Scholar 

  7. Mant AK (1969) Autopsy diagnosis of accidental hypothermia. J Forensic Med 16:126–129

    CAS  PubMed  Google Scholar 

  8. Büchner F (1943) Die pathologie der Unterkühlung. [in German]. Klin Wochenschr 22:89–92

    Article  Google Scholar 

  9. Preuβ J, Dettmeyer R, Lignitz E, Madea B (2004) Fatty degeneration in renal tubule epithelium in accidental hypothermia victims. Forensic Sci Int 141:131–135

    Article  Google Scholar 

  10. Yoshida C, Ishikawa T, Michiue T, Quan L, Maeda H (2011) Postmortem biochemistry and immunohistochemistry of chromogranin A as a stress marker with special regard to fatal hypothermia and hypothermia. Int J Legal Med 125(1):11–20

    Article  PubMed  Google Scholar 

  11. Palmiere C, Mangin P (2012) Postmortem biochemical investigations in hypothermia fatalities. Int J Legal Med. doi:10.1007/s00414-012-0738-y

  12. Preuβ J, Dettmeyer R, Poster S, Lignitz E, Madea B (2008) The expression of heat shock protein 70 in kidneys in cases of death due to hypothermia. Forensic Sci Int 176:248–252

    Article  Google Scholar 

  13. Gotohoda T, Kubo S, Kitamura O, Ishigami A, Tokunaga I (2001) Neuronal changes in the arcuate and hypoglossal nuclei of brain stem induced by head injury. Int J Legal Med 115:121–127

    Article  Google Scholar 

  14. Marschall S, Rothschild MA, Bohnert M (2006) Expression of heat-shock protein 70 (Hsp70) in the respiratory tract and lungs of fire victims. Int J Legal Med 120:355–359

    Article  CAS  PubMed  Google Scholar 

  15. Fekete A, Vanny A, Ver A, Rusai K, Müller V, Reusz G, Tulassay T, Szabo AJ (2006) Sex differences in heat shock protein 72 expression and localization in rats following renal ischemia-reperfusion injury. Am J Physiol Ren Physiol 291:F806–F811

    Article  CAS  Google Scholar 

  16. Ganter MT, Ware LB, Howard M, Roux J, Gartland B, Matthay MA, Fleshner M, Pittet JF (2006) Extracellular heat shock protein 72 is a marker of the stress protein response in acute lung injury. Am J Physiol Lung Cell Mol Physiol 291:L354–L361

    Article  CAS  PubMed  Google Scholar 

  17. McClung JP, Hasday JD, He JR, Montain SJ, Cheuvront SN, Sawka MN, Singh IS (2008) Exercise-heat acclimation in humans alters baseline levels and ex vivo heat inducibility of hsp72 and hsp90 in peripheral blood mononuclear cells. Am J Physiol Regul Integr Comp Physiol 294:R185–R191

    Article  CAS  PubMed  Google Scholar 

  18. Sreedharan R, Riordan M, Thullin G, Why SV, Siegel NJ, Kashgarian M (2011) The maximal cytoprotective function of the heat shock protein 27 is dependent on heat shock protein 70. Biochim Biophys Acta 1813:129–135

    Article  CAS  PubMed  Google Scholar 

  19. Tulapurkar ME, Asiegbu BE, Singh IS, Hasday JD (2009) Hyperthermia in the febrile range induces HSP72 expression proportional to exposure temperature but not to HSF-1 DNA-binding activity in human lung epithelial A549 cells. Cell Stress Chaperones 14:499–508

    Article  CAS  PubMed  Google Scholar 

  20. Galbo H, Houston ME, Christensen NJ, Holst JJ, Nielsen B, Nygaard E, Suzuki J (1979) The effect of water temperature on the hormonal response to prolonged swimming. Acta Physiol Scand 105(3):326–337

    Article  CAS  PubMed  Google Scholar 

  21. Miyatake N, Sakano N, Murakami S (2012) The relation between ambulance transports stratified by heat stroke and air temperature in all 47 prefectures of Japan in August, 2009: ecological study. Environ Health Prev Med 17:77–80

    Article  PubMed  Google Scholar 

  22. Barutta F, Pinach S, Giunti S, Vittone F, Forbes JM, Chiarle R, Arnstein M, Perin PC, Camussi G, Cooper ME, Gruden G (2008) Heat shock protein expression in diabetic nephropathy. Am J Physiol Ren Physiol 295:F1817–F1824

    Article  CAS  Google Scholar 

  23. Su J, Li SJ, Chen ZH, Zeng CH, Zhou H, Li LS, Liu ZH (2010) Evaluation of podocyte lesion in patients with diabetic nephropathy: Wilms’ tumor-1 protein used as a podocyte marker. Diabetes Res Clin Prac 87:167–175

    Article  CAS  Google Scholar 

  24. Caruccio L, Bae S, Liu AYC, Chen KY (1997) The heat-shock transcription factor HSF1 is rapidly activated by either hyper- or hypo-osmotic stress in mammalian cells. Biochem J 327:341–347

    CAS  PubMed  Google Scholar 

  25. Pirkkala L, Nykänen P, Sistonen L (2001) Roles of the heat shock transcription factors in regulation of the heat shock response and beyond. FASEB J 15:1118–1131

    Article  CAS  PubMed  Google Scholar 

  26. Neuhofer W, Müller E, Grünbein R, Thurau K, Beck FX (1999) Influence of NaCl, urea, potassium, and pH on HSP72 expression in MDCK cells. Pflügers Arch-Eur J Physiol 439:195–200

    Article  CAS  Google Scholar 

  27. Song L, Xu Z, Zhang C, Qiao X, Huang C (2009) Up-regulation of the HSP72 by Foxa1 in MCF-7 human breast cancer cell line. Biochem Biophys Res Commun 386:30–34

    Article  CAS  PubMed  Google Scholar 

  28. Ohtsuka K, Laszlo A (1992) The relationship between Hsp70 localization and heat resistance. Exp Cell Res 202:507–518

    Article  CAS  PubMed  Google Scholar 

  29. Morcillo G, Gorab E, Tanguay R, Diez J (1997) Specific intranucleolar distribution of Hsp70 during heat shock in polytene cells. Exp Cell Res 1:361–370

    Article  Google Scholar 

  30. Ohgitani E, Kobayashi K, Takeshita K, Imanishi J (1999) Biphasic translocation of a 70 kDa Heat shock protein in human cytomegalovirus-infected cells. J Gen Virol 80:63–68

    CAS  PubMed  Google Scholar 

  31. Ellis S, Killender M, Anderson R (2000) Heat induced alterations the localization of Hsp72 and Hsp73 as measured by indirect immunohistochemistry and immunogold electron microscopy. J Histochem Cytochem 48:321–331

    Article  CAS  PubMed  Google Scholar 

  32. Rada A, Tonino P, Anselmi G, Strauss M (2005) Is hypothermia a stress condition in HepG2 cells? Expression and localization of Hsp70 in human hepatoma cell line. Tissue Cell 37:59–65

    Article  CAS  PubMed  Google Scholar 

  33. Sonna LA, Kuhlmeier MM, Klatri P, Chen D, Lilly CM (2010) A microarray analysis of the effect of moderate hypothermia and rewarming on gene expression by human hepatocytes (HepG2). Cell Stress Chaperon 15:687–702

    Article  CAS  Google Scholar 

  34. Kyrou IE, Papakostas JC, Ioachim E, Koulouras V, Arnaoutoglou E, Angelidis C, Matsagkas MI (2012) Early ischaemic preconditioning of spinal cord enhanced the binding profile of heat shock protein 70 with neurofilaments and promoted its nuclear translocation after thoraco-abdominal aortic occlusion in pigs. Eur J Vasc Endovasc Surg 43:408–414

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The authors wish to thank the Medical Examiner’s Office of Hyogo Prefecture for providing some of the samples used in this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Makoto Sakurada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakurada, M., Asano, M., Takahashi, M. et al. Estimates of exposure to cold before death from immunohistochemical expression patterns of HSP70 in glomerular podocytes. Int J Legal Med 127, 783–790 (2013). https://doi.org/10.1007/s00414-012-0806-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-012-0806-3

Keywords

Navigation