Ionizing radiation induces blockade of c-Jun N-terminal kinasedependent cell death pathway in amanner correlated with p21Cip/WAF1 induction in primary cultured normal human fibroblasts.
- Author:
Eun Sook CHO
1
;
Seung Bum LEE
;
In Hwa BAE
;
Yun Sil LEE
;
Su Jae LEE
;
Hong Duck UM
Author Information
1. Laboratory of Radiation Tumor Physiology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea. hdum@kcch.re.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cell death;
fibroblasts;
hydrogen peroxide;
radiation, ionizing;
JNK mitogen-activated protein kinases
- MeSH:
Antioxidants/pharmacology;
Cell Death;
Cells, Cultured;
Enzyme Activation/radiation effects;
Fibroblasts/enzymology/radiation effects;
*Gamma Rays;
Heat-Shock Proteins/metabolism;
Humans;
JNK Mitogen-Activated Protein Kinases/*antagonists & inhibitors;
Oxidative Stress/*radiation effects;
Research Support, Non-U.S. Gov't;
Water/pharmacology
- From:Experimental & Molecular Medicine
2005;37(4):282-289
- CountryRepublic of Korea
- Language:English
-
Abstract:
During radiotherapy of cancer, neighboring normal cells may receive sub-lethal doses of radiation. To investigate whether such low levels of radiation modulate normal cell responses to death stimuli, primary cultured human fibroblasts were exposed to various doses of gamma-rays. Analysis of cell viability using an exclusion dye propidium iodide revealed that the irradiation up to 10 Gy killed the fibroblasts only to a minimal extent. In contrast, the cells efficiently lost their viability when exposed to 0.5-0.65 mM H2O2. This type of cell death was accompanied by JNK activation, and was reversed by the use of a JNK-specific inhibitor SP600125. Interestingly, H2O2 failed to kill the fibroblasts when these cells were pre-irradiated, 24 h before H2O2 treatment, with 0.25-0.5 Gy of gamma-rays. These cytoprotective doses of gamma-rays did not enhance cellular capacity to degrade H2O2, but elevated cellular levels of p21Cip/WAF1, a p53 target that can suppress H2O2-induced cell death by blocking JNK activation. Consistently, H2O2-induced JNK activation was dramatically suppressed in the pre-irradiated cells. The overall data suggests that ionizing radiation can impart normal fibroblasts with a survival advantage against oxidative stress by blocking the process leading to JNK activation.
