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
Experimental & Molecular Medicine
;
: 282-289, 2005.
Article
in English
| WPRIM
| ID: wpr-177643
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Water
/
Cells, Cultured
/
Cell Death
/
Oxidative Stress
/
JNK Mitogen-Activated Protein Kinases
/
Enzyme Activation
/
Fibroblasts
/
Gamma Rays
/
Heat-Shock Proteins
/
Antioxidants
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2005
Type:
Article
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