Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 42
Nuclear loss of Ku DNA repair protein in cells exposed to oxidative stress
Jong Hwa Lee, Ji Yeon Song, Ji Hoon Yu, Kyung Hwan Kim, Hyeyoung Kim*
Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei
University College of Medicine, Seoul 120-752, Korea. E-mail : pico798@naver.com
Recent studies show that NF-kB plays a critical role in protecting the cells from apoptotic
cell death. We previously demonstrated that oxidative stress – induced cell death is caused by
nuclear loss of DNA repair protein Ku proteins in pancreatic acinar AR42J cells. This study
aims to investigate the role of NF- kB on nuclear translocation of Ku proteins and apoptotic
cell death, induced by oxidative stress in AR42J cells. We examined Ku expression, cell
viability, and apoptosis of the cells treated with or without H2O2, which is continuously
generated by G/GO and in the caspase-3 inhibitor. Wild-type cells as well as the cells
transfected with Ku dominant negative gene or I-kB alpha mutant gene was used. As a result,
G/GO induced decrease in nuclear Ku70 and Ku80 time-and concentration-dependently.
G/GO induced alterations in Ku expression were inhibited, in part, by caspase-3 inhibitor.
G/GO induced apoptosis, which was in parallel with loss of nuclear Ku70 and Ku80 in the
cells transfected with the control pcDNA3 vector. G/GO increased apoptosis in those
transfected with Ku dominant negative mutant or I-kB alpha mutant gene. Nuclear level of Ku
proteins were decreased in the cells transfected with I-kB alpha mutant gene. Conclusively,
nuclear translocation of Ku proteins may be mediated by NF-kB in the cells. Decrease in
nuclear translocation of Ku proteins may result in apoptotic cell death in AR42J cells.
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