NF-κB activation plays an antiapoptotic role in human leukemic K562 cells exposed to ionizing radiation
✍ Scribed by Amelia Cataldi; Monica Rapino; Lucia Centurione; Nadia Sabatini; Giovanna Grifone; Francesco Garaci; Rosalba Rana
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 323 KB
- Volume
- 89
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Exposure of cells to ionizing radiation (IR) determines cellular lesions, such as DNA and membrane damage, which involve a coordinate network of signal transduction pathways responsible for resistance to or delay of apoptosis, depending on cell type and administered dose. Since, after IR exposure, the apoptotic profile appeared different in the two chosen cell lines K562 and Jurkat along with caspase‐3 activation, we paid attention to the influence exerted by Protein kinase C δ on transcription factor NF‐κB activation. Interestingly, K562 resist to IR carrying out a survival strategy which includes PKC δ/NF‐κB pathway activation, probably mediated by novel IKKs and a role for PI‐3‐kinase in activating PKC δ at Thr 505 by PDK‐1 phosphorylation is suggested. In addition, since caspase‐3 is not activated in these cells upon ionizing radiation exposure, it could be supposed that NF‐κB antagonizes apoptosis induction interfering with pathways which lead to caspase activation, may be by inducing expression of IAP, caspases 3, 7, 9, inhibitor. Thus NF‐κB activation explains the resistance displayed by K562 to IR and drug potential interference directed to this protein could overcome apoptosis resistance in clinical settings. J. Cell. Biochem. 89: 956–963, 2003. © 2003 Wiley‐Liss, Inc.