Document Detail


The Defect of Ku70 Affects Sensitivity to X-Ray and Radiation-Induced Caspase-Dependent Apoptosis in Lung Cells.
MedLine Citation:
PMID:  23149547     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The DNA repair protein Ku70 is a key player in chemoresistance to anticancer agents (e.g., etoposide) or radioresistance. The responses of different organs to radiation vary widely and likely depend on the cell population in the organs. Previously, we established and characterized Ku70-deficient murine lung epithelial (Ku70 -/- MLE) cells and found that these cells are more sensitive than Ku70 +/- MLE cells (control cells) to X-irradiation, as determined by clonogenic survival assay; however, the mechanism underlying this sensitivity remains unclear. In this study, we examined the mechanism by which X-irradiation triggers the death of Ku70 -/- MLE cells. Our results showed that Ku70 -/- MLE cells were more sensitive to radiation-induced apoptosis than control cells, although X-irradiation activated caspase-3 and caspase-7, and cleaved PARP in both cell lines. We also examined the expression level of phosphorylated H2AX (γH2AX), which is a marker of DSB, and observed the phosphorylation of H2AX and the elimination of γH2AX in both cell lines after X-irradiation. The elimination in Ku70 -/- MLE cells was slower than that in control cells, suggesting that DSB repair activity in the Ku70 -/- MLE cells is lower than that in control cells. These findings suggest that Ku70 might play a key role in the inhibition of apoptosis through the DSB repair pathway in lung epithelial cells. Our findings also suggest that these cell lines might be useful for the study of Ku70 functions and the Ku70-dependent DSB repair pathway in lung epithelial cells.
Authors:
Manabu Koike; Yasutomo Yutoku; Aki Koike
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  The Journal of veterinary medical science / the Japanese Society of Veterinary Science     Volume:  -     ISSN:  1347-7439     ISO Abbreviation:  J. Vet. Med. Sci.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9105360     Medline TA:  J Vet Med Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
DNA Repair Gene Res., National Institute of Radiological Sciences.
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