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Role of NF-κB and DNA Repair Protein Ku on Apoptosis in Pancreatic Acinar Cells

Authors
 JI YEON SONG  ;  JOO WEON LIM  ;  KYUNG HWAN KIM  ;  HYEYOUNG KIM 
Citation
 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, Vol.1010 : 259-263, 2003 
Journal Title
 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 
ISSN
 0077-8923 
Issue Date
2003
MeSH
Animals ; Antigens, Nuclear/metabolism* ; Apoptosis/physiology* ; Autoantigens/metabolism ; Cell Line ; Cell Nucleus/metabolism ; DNA-Binding Proteins/metabolism* ; Glucose Oxidase/metabolism ; Hydrogen Peroxide/metabolism ; Ku Autoantigen ; NF-kappa B/metabolism* ; Pancreas ; Protein Transport ; Rats
Keywords
15033730
Abstract
Reactive oxygen species have been known to cause DNA damage and induce apoptosis. During DNA damage, DNA repair proteins Ku70 and Ku80 prevent cell death, but severe DNA damage beyond the repair capacity of the DNA repair proteins triggers necrosis or apoptosis. Recent reports have shown that NF-κB plays a critical role in protecting the cells from apoptosis. We investigated whether glucose oxidase acting on β-D-glucose (G/GO), which continuously produces H2O2, induces apoptosis, and whether NF-κB and Ku are involved in G/GO-induced apoptosis in pancreatic acinar AR42J cells. Electron microscopic observation showed that apoptotic cells with characteristic nuclear condensation and shrinkage as well as large vacuoles were detected after G/GO treatment. G/GO treatment induced apoptotic cell death, as determined by viable cell count and DNA fragmentation. G/GO-induced apoptosis was increased in the cells transfected with the Ku-dominant negative mutant (Ku D/N) and mutated IκBα gene (IκB mt) as compared to the wild-type cells (Wild) and the cells transfected with the control pcDNA3 vector (pcN-3). G/GO treatment caused nuclear loss of both Ku70 and Ku80 in Wild cells and pcN-3 cells. Even without G/GO treatment, nuclear loss of Ku proteins was observed in IκB mt cells. These results suggest that oxidative stress-induced reduction of nuclear Ku proteins may cause loss of defense against DNA damage and thus induce apoptosis in pancreatic acinar cells. The novel finding is that nuclear translocation of Ku proteins may be mediated by NF-κB.
Full Text
http://onlinelibrary.wiley.com/doi/10.1196/annals.1299.044/abstract
DOI
OAK-2003-00062
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute of Gastroenterology (소화기병연구소) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Lim, Joo Weon(임주원)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/113222
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