PMID- 19326139
OWN - NLM
STAT- MEDLINE
DCOM- 20090915
LR  - 20211020
IS  - 1437-1596 (Electronic)
IS  - 0937-9827 (Linking)
VI  - 123
IP  - 4
DP  - 2009 Jul
TI  - Determining time of death: temperature-dependent postmortem changes in 
      calcineurin A, MARCKS, CaMKII, and protein phosphatase 2A in mouse.
PG  - 305-14
LID - 10.1007/s00414-009-0343-x [doi]
AB  - While the determination of postmortem interval (PMI) is a crucial and fundamental 
      step in any death investigation, the development of appropriate biochemical 
      methods for PMI estimation is still in its infancy. This study focused on the 
      temperature-dependent postmortem degradation of calcineurin A (CnA), 
      calmodulin-dependent kinase II (CaMKII), myristoylated alanine-rich C-kinase 
      substrate (MARCKs), and protein phosphatase 2A (PP2A) in mice. The results show 
      that MARCKS, CaMKII, and the use of lung tissue do not appear to warrant further 
      study for the determination of PMI in humans. In skeletal muscle, CnA underwent a 
      rapid temperature-dependent cleavage (60 --> 57 kDa) over the first 48 h of 
      postmortem interval. At 21 degrees C, this transformation was completed within 24 
      h. In contrast, PP2A increased within the first 24 h after which it degraded at 
      21 degrees C but remained stable for up to 96 h at 5 degrees C and 10 degrees C. 
      The 60 --> 57 kDa postmortem conversion of CnA was inhibited by addition of 
      protease inhibitors and MDL-28170 indicating a calpain pathway mediates this 
      breakdown. Proteasome inhibition (MG-132) and calmodulin antagonism 
      (calmidazolium) also inhibited this conversion suggesting that other protein 
      degradation pathways also are in play. In contrast, all of the protease 
      inhibitors and calmidazolium but not ethylene glycol tetraacetic acid led to 
      increased levels of PP2A. The data are discussed in terms of developing a useable 
      field-based biochemical assay for postmortem interval determination in humans and 
      understanding the protein degradation pathways that are initiated upon death.
FAU - Poloz, Yekaterina O
AU  - Poloz YO
AD  - Department of Cell & Systems Biology, University of Toronto, Toronto ON M5S3G5, 
      Canada.
FAU - O'Day, Danton H
AU  - O'Day DH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090327
PL  - Germany
TA  - Int J Legal Med
JT  - International journal of legal medicine
JID - 9101456
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Leupeptins)
RN  - 0 (MARCKS protein, human)
RN  - 0 (Marcks protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 125267-21-2 (Myristoylated Alanine-Rich C Kinase Substrate)
RN  - 4R9H38JAWL (calmidazolium)
RN  - 526U7A2651 (Egtazic Acid)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 3.1.3.16 (Calcineurin)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - EC 3.4.22.- (Calpain)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Calcineurin/*metabolism
MH  - Calcium/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism
MH  - Calpain/metabolism
MH  - Centrifugation
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Egtazic Acid/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Forensic Pathology
MH  - Imidazoles/pharmacology
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Leupeptins/pharmacology
MH  - Lung/metabolism
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Muscle, Skeletal/metabolism
MH  - Myristoylated Alanine-Rich C Kinase Substrate
MH  - *Postmortem Changes
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Phosphatase 2/*metabolism
MH  - *Temperature
EDAT- 2009/03/28 09:00
MHDA- 2009/09/16 06:00
CRDT- 2009/03/28 09:00
PHST- 2008/10/30 00:00 [received]
PHST- 2009/03/16 00:00 [accepted]
PHST- 2009/03/28 09:00 [entrez]
PHST- 2009/03/28 09:00 [pubmed]
PHST- 2009/09/16 06:00 [medline]
AID - 10.1007/s00414-009-0343-x [doi]
PST - ppublish
SO  - Int J Legal Med. 2009 Jul;123(4):305-14. doi: 10.1007/s00414-009-0343-x. Epub 
      2009 Mar 27.