Open AccessIonizing radiation induces blockade of c-Jun N-terminal kinase-dependent cell death pathway in a manner correlated with p21Cip/WAF1 induction in primary cultured normal human fibroblasts
Author(s) -
Eun Sook Cho,
Seung Bum Lee,
In Hwa Bae,
Yun Sil Lee,
Su Jae Lee,
Hong Duck Um
Publication year - 2005
Publication title -
experimental and molecular medicine/experimental and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.703
H-Index - 82
eISSN - 2092-6413
pISSN - 1226-3613
DOI - 10.1038/emm.2005.38
Subject(s) - programmed cell death , propidium iodide , apoptosis , ionizing radiation , viability assay , c jun , biology , fibroblast , cancer research , kinase , microbiology and biotechnology , cell , oxidative stress , cell culture , irradiation , biochemistry , physics , genetics , gene , nuclear physics , transcription factor
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 H(2)O(2). This type of cell death was accompanied by JNK activation, and was reversed by the use of a JNK-specific inhibitor SP600125. Interestingly, H(2)O(2) failed to kill the fibroblasts when these cells were pre-irradiated, 24 h before H(2)O(2) treatment, with 0.25-0.5 Gy of gamma-rays. These cytoprotective doses of gamma-rays did not enhance cellular capacity to degrade H(2)O(2), but elevated cellular levels of p21(Cip/WAF1), a p53 target that can suppress H(2)O(2)-induced cell death by blocking JNK activation. Consistently, H(2)O(2)-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.