Quantitative Analyses of Postmortem Heat Shock Protein mRNA Profiles in the Occipital Lobes of Human Cerebral Cortices: Implications in Cause of Death

Abstract

Quantitative RNA analyses of autopsy materials to diagnose the cause and mechanism of death are challenging tasks in the field of forensic molecular pathology. Alterations in mRNA profiles can be induced by cellular stress responses during supravital reactions as well as by lethal insults at the time of death. Here, we demonstrate that several gene transcripts encoding heat shock proteins (HSPs), a gene family primarily responsible for cellular stress responses, can be differentially expressed in the occipital region of postmortem human cerebral cortices with regard to the cause of death. HSPA2 mRNA levels were higher in subjects who died due to mechanical asphyxiation (ASP), compared with those who died by traumatic injury (TI). By contrast, HSPA7 and A13 gene transcripts were much higher in the TI group than in the ASP and sudden cardiac death (SCD) groups. More importantly, relative abundances between such HSP mRNA species exhibit a stronger correlation to, and thus provide more discriminative information on, the death process than does routine normalization to a housekeeping gene. Therefore, the present study proposes alterations in HSP mRNA composition in the occipital lobe as potential forensic biological markers, which may implicate the cause and process of death.

Postmortem mRNA Expression Patterns in Left Ventricular Myocardial Tissues and Their Implications for Forensic Diagnosis of Sudden Cardiac Death

“…Rather, pairwise analyses of a set of gene transcripts with concurrently changed, but negatively correlated under certain pathological condition, appeared to be more practical for forensic applications as we previously demonstrated (Chung et al, 2012). As shown in Fig.…”

“…Total RNA was isolated from 20–50 mg tissue using the RNeasy mini kit (QIAGEN) and then quantified by spectrophotometry. Gene expression profiling by microarray analysis was performed to explore SCD-associated human RNA transcripts as described previously with minor modifications ( Chung et al, 2012 ). Group-pooled cardiac RNA samples representing TD, CC, MI, and NI cases were subjected to microarray analysis.…”

“…Indeed, extensive studies are currently been carried out to address key issues in forensic science regarding the cause and process of death, postmortem interval, and pathophysiological conditions of diseases and injuries ( Maeda et al, 2010 ; Vennemann and Koppelkamm, 2010a ). Distinct RNA compositions in autopsy materials have been proposed to imply certain causes and circumstances of death ( Chen et al, 2012 ; Chung et al, 2012 ; Ikematsu et al, 2005 ; Miyazato et al, 2012 ; Takahashi et al, 2009 ; Zhao et al, 2006 ; 2009 ; Zhu et al, 2008 ). Notably, Maeda and colleagues proposed that left ventricular (LV) expression profiles of several mRNA species encoding hypoxia-inducible factor 1α and natriuretic peptides were relatively higher in autopsy materials of cardiac death subjects, particularly those from subjects with ischemic heart injuries ( Chen et al, 2012 ; Zhu et al, 2008 ).…”

Gene Expression Pattern Analysis for Forensic Diagnosis of Sudden Cardiac Death

“…Ischemia (11)(12)(13) can cause increase of mRNA levels of HSPA1.They are also reported to be increased in brain after drowning in greater intensity; when compared with other cases of ASP (14). HSPA1 mRNA poses as a potential marker for SCD in acute cases, but have not been expressed significantly (15) during cellular stress (usefulness not concluded).…”

“…Attempts were made to analyse HSP mRNA transcripts in postmortem occipital lobes to differentiate causes of death, such as traumatic injury (TI), mechanical asphyxiation (ASP) and sudden cardiac death (SCD) (15).…”