Expression of a dominant negative I kappa B-alpha modulates hypersensitivity of ataxia telangiectasia fibroblasts to streptonigrin-induced apoptosis.
Ataxia telangiectasia (AT) cells exhibit greater levels of apoptosis than normal fibroblasts following exposure to X-rays or radiomimetic drugs. In this study, we investigated apoptosis in AT cells whose radiation sensitivity has been altered by transfection with a cDNA expressing truncated I kappa B-alpha (delta I kappa B-alpha). delta I kappa B-alpha functions as a dominant negative regulatory protein of NF-kappa B. The transfected cells (ATCL11) were compared to parental cells after treatment with the radiomimetic drug streptonigrin. ATCL11 cells exposed to streptonigrin demonstrated less apoptosis (approximately 2%) at 24 hr than did parental AT cells (approximately 24%). These data indicate that the mechanisms underlying apoptosis induction by streptonigrin are modulated by regulation of NF-kappa B.
Jung
M
M
Department of Radiation Medicine, Georgetown University Medical Center, Washington, D.C., USA. Jungm@gunct.georgetown.edu
Zhang
Y
Y
Dritschilo
A
A
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D001260:Ataxia Telangiectasia / Q000503:physiopathology*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D018076:DNA, Complementary / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D004351:Drug Resistance; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010641:Phenotype; D013308:Streptonigrin / Q000494:pharmacology
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D013308:Streptonigrin