ER stress related factor ATF6 and caspase-12 trigger apoptosis in neonatal hypoxic-ischemic encephalopathy

Int J Clin Exp Pathol. 2015 Jun 1;8(6):6960-6. eCollection 2015.

Abstract

The specific and available markers proteins of neonatal hypoxic-ischemic encephalopathy (HIE) injury are correlated with disease severity and the disability in childhood. Exploring the mechanism of HIE is very helpful to the targeted therapeutic approach in clinical. This study aims to explore the cell death-related proteins or biomarkers that plays roles in the HIE injury. In this study, 15 patients were included the 487 autopsies patients performed at the Department of Pathology. The lactate dehydrogenase (LDH) assay was used to detect the cell viability of NGF-differentiated PC12 cell. TUNEL assay was employed to examine the apoptotic cells in embedded slides samples. Three ER stress-related protein, including ATF6, p-Perk and IRE-1 were investigated using Western blot assay for the ER stress examination. The apoptosis associated caspase-12 and CHOP protein were detected by Western blot. The results indicated that LDH activity of living cells during hypoxia was significantly enhanced to 45% and 64% after 8 hours and 24 hours. The TUNEL results showed that plenty of the PC12 cells became the positive staining cells when treated with 0.1% O2 hypoxia. ER stress UPR pathway protein, cleaved ATF6, was increased significantly when treated with 0.1% O2 compared with the cells treated with 20% O2. Furthermore, the caspase 12 activation was triggered when the cells treated with the 0.1% O2. In conclusion, apoptosis is served as an important factor that triggers the HIE brain injury through cleaving the ATF6 and caspase-12 ER stress-related protein.

Keywords: ATF6; ER stress; apoptosis; caspase-12; neonatal hypoxic-ischemic encephalopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 6 / metabolism*
  • Animals
  • Apoptosis*
  • Autopsy
  • Biomarkers / metabolism
  • Brain / enzymology*
  • Brain / pathology
  • Caspase 12 / metabolism*
  • Cell Hypoxia
  • Cell Survival
  • Endoplasmic Reticulum / enzymology*
  • Endoplasmic Reticulum / pathology
  • Endoplasmic Reticulum Stress*
  • Female
  • Humans
  • Hypoxia-Ischemia, Brain / enzymology*
  • Hypoxia-Ischemia, Brain / mortality
  • Hypoxia-Ischemia, Brain / pathology
  • Infant, Newborn
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Neurons / enzymology
  • Neurons / pathology
  • PC12 Cells
  • Rats
  • Signal Transduction
  • Time Factors

Substances

  • ATF6 protein, human
  • Activating Transcription Factor 6
  • Atf6 protein, rat
  • Biomarkers
  • L-Lactate Dehydrogenase
  • CASP12 protein, human
  • Casp12 protein, rat
  • Caspase 12