Proteome analysis of cardiomyocyte proteins in forensic autopsy cases and application to forensic pathological diagnosis

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590580
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Nagasaki University
• Principal Investigator: TSUDA Ryouichi Nagasaki University, Graduate School of Biomedical Sciences, Lecture, 大学院医歯薬学総合研究科, 講師 (20098875)
• Co-Investigator(Kenkyū-buntansha): NAKASONO Ichiro Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (30108287) ; IKEMATSU Kazuya Nagasaki University, Graduate School of Biomedical Sciences, Assistant professor, 大学院医歯薬学総合研究科, 助教授 (80332857)
• Project Period (FY): 2005 – 2006
• Keywords: biomolecular / protein / cardiomyocyte / two-dimensional gel electrophoresis / proteome / forensic molecular pathology / forensic pathological diagnosis / social medicine

Research Abstract

We performed a differential proteomic profiling study on expression changes of cardiomyocyte proteins ; desmin, troponin T, gelsolin, α-smooth muscle actin (α-SMA), manganese superoxide dismutase (MnSOD) and α-enolase in left ventricular muscles of forensic autopsy cases by two-dimensional gel electrophoresis.
1.Desmin : Des min abnormalities were reported in cardiomyopathy and heart failure cases. The significant differences were found between asphyxia and sudden cardiac death (p<0.03), and head injury (p<0.02), between bleeding and head injury (p<0.05) in the ratio of phosphorylated to dephosphorylated desmin.
2. Gelsolin : Gelsolin is an abundant actin binding protein and the protein expression was increased in cardiomyopathic case. We demonstrate that isoelectric point (pI) of several gelsolin spots shifted to acidic region in 16 cases.
3. Troponin T: Cardiac troponin T is an essential component of the cardiac contraction regulations and the sensitivity of cardiac myofilaments to calcium. We detected altered troponin T spots in addition to original spots in 5. In 6 cases, we couldn't find the tropnin T spots.
4. α-SMA : In experimental rat models, hypertrophic stimuli induce early expression of 'fetal genes' including α-SKA and α-SMA. The expression of α-SMA in 51 forensic autopsy cases was divided into 3 groups : 1. Strong (n=9), 2. Moderate (n=21), 3. Weak or Negative (n=21).
5. MnSOD : MnSOD is one of the main antioxidant enzymes that protect the heart against ischemia-reperfusion injury. In 19 cases, a new MnSOD spot was detected in basic region.
6. α-Enolase : α-Enolase is a glycolytic enzyme and the enzyme expression is observed in rat heart subjected ischemia-reperfusion injury. We demonstrated over a two-fold overexpression of α-enolase in 19 cases including four sudden cardiac death cases.