Nuclear loss of DNA repair Ku proteins and c-myc expression in apoptosis of cerulein-stimulated pancreatic acinar cells.
Cerulein induces oxidative stress and an acute, edematous form of pancreatitis. Cell death linked to oxidative DNA damage has been implicated in acute pancreatitis. During DNA damage, DNA repair proteins, Ku70 and Ku80, prevent cell death but severe DNA damage triggers apoptosis. This study aims to investigate the role of Ku70 and Ku80 on apoptotic cell death, induced by cerulein in pancreatic acinar AR42J cells. We examined Ku expression, Ku-DNA binding activity, cell viability and mRNA expression of c-myc of the cells stimulated with cerulein. As a result, cerulein induced decrease in nuclear Ku70 and Ku80 with increase in cytoplasmic Ku proteins. Cerulein decreased Ku-DNA binding activity in parallel with increase in cell death and mRNA expression of c-myc. Conclusively, nuclear loss of Ku70 and Ku80 may cause the loss of defense against DNA damage and apoptosis in pancreatic acinar cells stimulated with cerulein.
Yu
J H
JH
Department of Pharmacology, Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul, 120-752, Korea.
Kim
K H
KH
Kim
H
H
D000818:Animals; D034961:Antigens, Nuclear / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D002452:Cell Count; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002108:Ceruletide / Q000494:pharmacology*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D000072200:Ku Autoantigen; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D005765:Gastrointestinal Agents; D012333:RNA, Messenger; D002108:Ceruletide; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen