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Role of NF‐κB and DNA Repair Protein Ku on Apoptosis in Pancreatic Acinar Cells
Author(s) -
SONG JI YEON,
LIM JOO WEON,
KIM HYEYOUNG,
KIM KYUNG HWAN
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.044
Subject(s) - apoptosis , ku70 , ku80 , dna damage , transfection , dna fragmentation , dna repair , programmed cell death , biology , microbiology and biotechnology , proliferating cell nuclear antigen , nuclear protein , chemistry , dna , biochemistry , gene , transcription factor , dna binding protein
A bstract : 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 H 2 O 2 , 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.