ER stress induced by ionising radiation in IEC-6 cells

Int J Radiat Biol. 2010 Jun;86(6):429-35. doi: 10.3109/09553001003668014.

Abstract

Purpose: Ionising radiation (IR) can evoke a series of biochemical events inside the cell. However, whether IR can directly induce endoplasmic reticulum (ER) stress is not clear. In our previous study, we found that there might be a causative link between IR and ER stress. In this study, we further characterised the type of ER stress induced by IR.

Materials and methods: Rat intestinal epithelial cells IEC-6 were irradiated at a dose of 10 Gy, and total RNA and proteins were harvested at indicated time points. The mRNA and protein expression of immunoglobulin heavy chain binding protein (BiP) and glucose regulated protein 94 (GRP94) was detected along with proteins associated with ER stress signal pathways.

Results: Our results indicated that IR induced up-regulation of ER stress marker including BiP and GRP94 at protein and mRNA levels in IEC-6 cells. Increased phosphorylation of eukaryotic translation initiation factor 2 (eIF2alpha) and induced mRNA splicing of X-box binding protein 1 (XBP1) suggested that PERK (interferon-induced double-stranded RNA-activated protein kinase (PRKR) -like endoplasmic reticulum kinase) and IRE1 (inositol requirement 1) signal transduction pathways were involved in this kind of ER stress. However, the active form of activating transcription factor 6 (ATF6) did not change significantly in irradiated cells, which suggested that the ATF6 pathway was not involved.

Conclusions: Thus, we concluded that IR could induce moderate ER stress directly in IEC-6 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 6 / metabolism
  • Animals
  • Biomarkers / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / radiation effects*
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / radiation effects*
  • Heat-Shock Proteins / metabolism
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism
  • Protein Biosynthesis / radiation effects
  • Protein Serine-Threonine Kinases / metabolism
  • Radiation, Ionizing
  • Rats
  • Signal Transduction / radiation effects
  • Stress, Physiological / radiation effects*
  • Transcription, Genetic / radiation effects
  • Up-Regulation / radiation effects
  • eIF-2 Kinase / metabolism

Substances

  • Activating Transcription Factor 6
  • Atf6 protein, rat
  • Biomarkers
  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • endoplasmin
  • Ern2 protein, rat
  • PERK kinase
  • Protein Serine-Threonine Kinases
  • eIF-2 Kinase