Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

Eun Sang Lee, Hae June Lee, Yoon Jin Lee, Jae Hoon Jeong, Seong Man Kang, Young Bin Lim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

Original languageEnglish
Pages (from-to)1005-1009
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number2
DOIs
Publication statusPublished - 2014 Jul 25

Fingerprint

Endoplasmic Reticulum Stress
Ionizing radiation
Cell death
Ionizing Radiation
Cell Death
Epithelial Cells
Unfolded Protein Response
Chemical activation
Intestinal Mucosa
Apoptosis
Caspase 3
Wounds and Injuries
Tunicamycin
Thapsigargin
Radiation Tolerance
Radiotherapy
DNA Fragmentation
Abdomen
Small Interfering RNA
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells. / Lee, Eun Sang; Lee, Hae June; Lee, Yoon Jin; Jeong, Jae Hoon; Kang, Seong Man; Lim, Young Bin.

In: Biochemical and Biophysical Research Communications, Vol. 450, No. 2, 25.07.2014, p. 1005-1009.

Research output: Contribution to journalArticle

Lee, Eun Sang ; Lee, Hae June ; Lee, Yoon Jin ; Jeong, Jae Hoon ; Kang, Seong Man ; Lim, Young Bin. / Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 450, No. 2. pp. 1005-1009.
@article{a4bb5d182ebf4e2ea81a6c86e14a5e3a,
title = "Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells",
abstract = "Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.",
keywords = "Chemical chaperone, Endoplasmic reticulum stress, Ionizing radiation, Unfolded protein response",
author = "Lee, {Eun Sang} and Lee, {Hae June} and Lee, {Yoon Jin} and Jeong, {Jae Hoon} and Kang, {Seong Man} and Lim, {Young Bin}",
year = "2014",
month = "7",
day = "25",
doi = "10.1016/j.bbrc.2014.06.091",
language = "English",
volume = "450",
pages = "1005--1009",
journal = "The BMJ",
issn = "0730-6512",
publisher = "Kluwer Academic Publishers",
number = "2",

}

TY - JOUR

T1 - Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

AU - Lee, Eun Sang

AU - Lee, Hae June

AU - Lee, Yoon Jin

AU - Jeong, Jae Hoon

AU - Kang, Seong Man

AU - Lim, Young Bin

PY - 2014/7/25

Y1 - 2014/7/25

N2 - Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

AB - Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

KW - Chemical chaperone

KW - Endoplasmic reticulum stress

KW - Ionizing radiation

KW - Unfolded protein response

UR - http://www.scopus.com/inward/record.url?scp=84905106478&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905106478&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2014.06.091

DO - 10.1016/j.bbrc.2014.06.091

M3 - Article

VL - 450

SP - 1005

EP - 1009

JO - The BMJ

JF - The BMJ

SN - 0730-6512

IS - 2

ER -