ER stress-related protein, CHOP, may serve as a biomarker of mechanical asphyxia: a primary study

Int J Legal Med. 2022 Jul;136(4):1091-1104. doi: 10.1007/s00414-021-02770-1. Epub 2022 Feb 4.

Abstract

The precise authentication of death from mechanical asphyxia (DMA) has been a complex problem in forensic medicine. Besides the traditional methods that concern the superficial characterization of the body, researchers are now paying more attention to the biomarkers that may help the identification of DMA. It has been reported that the extremely hypoxic environment created by DMA can cause the specific expression of mitochondria-related protein, which may sever as the biomarkers of DMA authentication. Since endoplasmic reticulum stress (ER stress) has been found to be related to the dysfunction of mitochondria, it is promising to look for the biomarkers of DMA among ER stress-related proteins. In this article, animal and cell experiments were conducted to examine how ER-mitochondria interaction may be influenced in the hypoxic condition caused by DMA primarily. Human samples were then used to verify the possible biomarkers of DMA. We found that ER stress-related protein CHOP was significantly up-regulated within a short-term postmortem interval (PMI) in brain tissue of DMA samples, which may interact with a series of ER stress- and mitochondria-related protein, leading to the apoptosis of the cells. It was also verified in human samples that the expression level of CHOP can sever as a potential biomarker of DMA within a specific PMI.

Keywords: Cause of death; ER stress; Forensic pathology; Mechanical asphyxia; Mitochondria.

MeSH terms

  • Animals
  • Apoptosis
  • Asphyxia*
  • Biomarkers
  • Endoplasmic Reticulum Stress*
  • Humans
  • Hypoxia
  • Transcription Factor CHOP / metabolism

Substances

  • Biomarkers
  • Transcription Factor CHOP